Article

A low dietary intake of cod protein is sufficient to increase growth, improve serum and tissue fatty acid compositions, and lower serum postprandial glucose and fasting non-esterified fatty acid concentrations in obese Zucker fa/fa rats

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Abstract

Purpose: Studies in rats suggest that fish proteins may improve lipid and glucose regulation and could thus be a potential tool in the treatment of obesity-related comorbidities. To date, all published rat studies on dietary fish protein have been designed with 50 or 100 % of dietary proteins from fish. As it is not common, nor advised, to consume fish as the only protein source in a healthy diet, mechanistic studies on the effects of diets with low dose fish proteins are needed. Here, we investigate whether a low dose of cod protein would affect glucose homeostasis and lipid metabolism in obese Zucker fa/fa rats. Methods: Twelve male obese Zucker fa/fa rats consumed diets where cod proteins accounted for 25 % of the total protein intake with the remaining 75 % from casein (COD) or 100 % of protein as casein (CAS) for 4 weeks. Results: Rats fed COD achieved a higher body weight without affecting adiposity and thigh muscle mass after 4 weeks, but liver weight and hepatic cholesterol level were higher than in CAS-fed rats. Fasting serum level of non-esterified fatty acids and 2 h postprandial glucose level were lower in COD than in CAS. The fatty acid metabolism was beneficially affected by the COD diet, with e.g., higher ratio of n-3/n-6 PUFAs in serum, liver and adipose tissue when compared to CAS. Conclusions: A low intake of cod protein (25 % of protein intake) was sufficient to beneficially affect lipid metabolism and postprandial glucose regulation in obese fa/fa rats.

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... Cod protein increased insulin-stimulated glucose uptake in white tibialis, white gastrocnemius, red gastrocnemius, quadriceps, extensor digitorum longus (EDL) muscle, heart and as well slightly in brown adipose tissue (BAT) (Lavigne et al. 2001). Contrarily, in the study of Drotningsvik et al. according to biochemical analysis neither of the diets, cod-nor casein-diet (20% protein from casein/whey (90% casein, 10% whey), could demonstrate glucoregulatory effect (glucose and insulin concentrations, glucose to insulin ratio, serum α-amylase) in obese Zucker fa/fa rats (Drotningsvik et al. 2015). ...
... Fatty acid metabolism of the obese animals was likewise considerably affected by cod-diet compared to casein diet; total n-3 PUFA level in epididymal WAT (eWAT), n-3/n-6 PUFA ratio in serum, liver and eWAT, and anti-inflammatory fatty acid index (AIFAI) in serum, liver, skeletal muscle and eWAT (Drotningsvik et al. 2015). Menhaden oil-cod protein combined diet, however, could not reduce serum TG levels compared with other protein-lipid diets in rats (Demonty, Deshaies, and Jacques 1998). ...
... In agreement, cod diet (23% (w/w) protein diet) had insignificant effect on fasting plasma concentrations of non-esterified fatty acids (NEFA) and TG in high fat diet fed rats (Lavigne et al. 2001). Nonetheless, cod-diet was superior to casein-diet (14% and 36% higher L/A and M/G, respectively) in reducing the serum concentration of NEFA (Drotningsvik et al. 2015). In contrary, neither cod-nor casein-diets (20% protein from casein/whey (90% casein and 10% whey)) could have hypolipidemic effects (insignificant effects on lipase and alanine transaminase concentrations, plasma TNF-α levels, serum TC, HDL/ LDL cholesterol, total BA and triacylglycerol concentrations) in obese Zucker fa/fa rats (Drotningsvik et al. 2015). ...
Article
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The definition of metabolic syndrome (MetS) fairly varies from one to another guideline and health organization. Per description of world health organization, occurrence of hyperinsulinemia or hyperglycemia in addition to two or more factors of dyslipidemia, hypoalphalipoproteinemia, hypertension and or large waist circumference factors would be defined as MetS. Conventional therapies and drugs, commonly with adverse effects, are used to treat these conditions and diseases. Nonetheless, in the recent decades scientific community has focused on the discovery of natural compounds to diminish the side effects of these medications. Among many available bioactives, biologically active peptides have notable beneficial effects on the management of diabetes, obesity, hypercholesterolemia, and hypertension. Marine inclusive of fish peptides have exerted significant bioactivities in different experimental in-vitro, in-vivo and clinical settings. This review exclusively focuses on studies from the recent decade investigating hypoglycemic, hypolipidemic, hypercholesterolemic and anti-obesogenic fish and fish peptides. Related extraction, isolation, and purification methodologies of anti-MetS fish biopeptides are reviewed herein for comparison purposes only. Moreover, performance of biopeptides in simulated gastrointestinal environment and structure-activity relationship along with absorption, distribution, metabolism, and excretion properties of selected oligopeptides have been discussed, in brief, to broaden the knowledge of readers on the design and discovery trends of anti-MetS compounds.
... In the present study, fish protein was added to the feed in an amount closer to what is recommended for the human population, that is, 25 % of total protein content. We have recently shown that replacing 25 % of the casein in a regular American Institute of Nutrition (AIN)-93G diet (39) with cod fillet protein resulted in lower postprandial glucose concentration when fed to obese Zucker fa/fa rats (40) and when taken as supplement cod protein reduced postprandial glucose in overweight and obese adults (41) . In line with this, others also report on improved glucose regulation after cod protein intake in animal and clinical studies (28,29,42) . ...
... This study was designed to investigate the effects of a diet containing cod protein on glucose regulation, lipid metabolism and growth. Based on our previous findings that cod protein seems to improve postprandial glucose regulation and growth (40) , and the knowledge that obese Zucker fa/fa rats spontaneously develop kidney failure (15,16) , the primary outcome of the present study was to investigate whether these cod protein fed Zucker fa/fa rats had a better kidney function and better utilisation of dietary protein when compared with rats fed a control diet. Instead of conducting a new rat experiment, and in line with The Three Rs of animal experiments (reduction, refinement and replacement), we chose to do more analyses using the biological samples from the same experiment. ...
... Some differences were also seen between the two diets for the non-essential amino acids; the COD diet contained higher concentrations of aspartic acid + asparagine, glycine and alanine and lower concentrations of glutamic acid + glutamine and proline when compared with the CAS diet. The COD diet contained 0·25 g EPA and 0·62 g DHA per kg, whereas long-chain n-3 PUFA were not found in the CAS diet (40) . ...
Article
Obesity increases the risk for developing kidney disease, and protection of kidneys through changes in diet should be investigated. Fish intake has been associated with reduced risk of developing kidney disease; therefore, we wanted to investigate whether cod protein intake could prevent or delay the development of kidney damage in an obese rat model that spontaneously develops proteinuria and focal segmental glomerulosclerosis. The aim of the study was to investigate any effects of cod protein intake on established markers of kidney function, amino acid composition, protein utilisation and growth in obese Zucker fa/fa rats in the early stage of decreased renal function. Male obese Zucker fa/fa rats (HsdOla:Zucker-Lepr) were fed cod muscle proteins in an amount corresponding to 25 % of dietary protein, with the remaining protein from a casein/whey mixture (COD diet). A control group was fed a diet with a casein/whey mixture as the only protein source (CAS diet). The intervention started when rats were 9–10 weeks old, and the rats were fed these diets for 4 weeks. At the end of the study, rats fed the COD diet had lower urine concentration of cystatin C, T-cell immunoglobulin mucin-1 (TIM-1), amino acids, carbamide, uric acid and ammonium and higher concentrations of creatine, trimethylamine N -oxide, 1-methylhistidine and 3-methylhistidine, lower kidney concentration of TIM-1 and showed better growth when compared with the CAS group. To conclude, cod protein may have the potential to delay the development of kidney damage in young obese Zucker rats and to improve protein utilisation and growth.
... The health benefits of fish consumption, especially of fatty fish, have traditionally been attributed to the effect of long-chain n-3 PUFA, and although the TAG-lowering effect of fish oil and long-chain n-3 PUFA is well documented, there is controversy as to the cholesterol-regulating and glucose-regulating effects of the marine n-3 fatty acids (1)(2)(3)(4)(5)(6)(7)(8)(9) . Studies in rats and humans suggest that also fish proteins, either eaten as fish or purified intact or hydrolysed proteins, may be beneficial to human health and affect risk factors of CVD and type 2 diabetes (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) . Little is known about how protein hydrolysates containing small peptides from fatty fish, such as herring and salmon, may affect markers of obesity-related disorders. ...
... Peptide size distributions were measured by combining results from HPLC size exclusion chromatography using a Superdex™ Peptide 10/300 GL column (measuring range 200-20 000 g/mol; GE Healthcare) and a TSKgel G2000SW column (measuring range 2000-70 000 g/mol; Tosoh), both equipped with UV detectors (30) . The fatty acid composition in the diets was analysed by GC, as previously described (21,(31)(32)(33)(34) . Identification of bioactive motifs in the water-soluble herring and salmon hydrolysates was performed by the International Research Institute of Stavanger (IRIS), as described by Pampanin et al. (26) , using LC-MS/MS Orbitrap analyses. ...
... Lipids were extracted from liver, skeletal muscle and faeces by the method of Bligh & Dyer (31) , and analysed as previously described (21) . ...
Article
The world’s fisheries and aquaculture industries produce vast amounts of protein-containing by-products that can be enzymatically hydrolysed to smaller peptides and possibly be used as additives to functional foods and nutraceuticals targeted for patients with obesity-related metabolic disorders. To investigate the effects of fish protein hydrolysates on markers of metabolic disorders, obese Zucker fa/fa rats consumed diets with 75 % of protein from casein/whey (CAS) and 25 % from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material, or 100 % protein from CAS for 4 weeks. The fatty acid compositions were similar in the experimental diets, and none of them contained any long-chain n -3 PUFA. Ratios of lysine:arginine and methionine:glycine were lower in HER and SAL diets when compared with CAS, and taurine was detected only in fish protein hydrolysate diets. Motifs with reported hypocholesterolemic or antidiabetic activities were identified in both fish protein hydrolysates. Rats fed HER diet had lower serum HDL-cholesterol and LDL-cholesterol, and higher serum TAG, MUFA and n -3: n -6 PUFA ratio compared with CAS-fed rats. SAL rats gained more weight and had better postprandial glucose regulation compared with CAS rats. Serum lipids and fatty acids were only marginally affected by SAL, but adipose tissue contained less total SFA and more total n -3 PUFA when compared with CAS. To conclude, diets containing hydrolysed rest raw material from herring or salmon proteins may affect growth, lipid metabolism, postprandial glucose regulation and fatty acid composition in serum and adipose tissue in obese Zucker rats.
... Cardiovascular disease is one of the leading causes of death worldwide and elevated circulating cholesterol is considered an important risk factor for the development of this disease [2]. Some fish proteins have shown promising effects on cholesterol metabolism in obese Zucker fa/fa rats but the effects seem to differ among proteins from various fish species, such as herring, salmon, and cod, and among protein fractions with different peptide sizes [12,15,27,28]. In the present study, we show that feeding obese Zucker fa/fa rats a diet with water-soluble protein from blue whiting as 1/3 of the total dietary protein content leads to lower serum and liver cholesterol concentrations. ...
... We have previously found lower serum LDL and HDL cholesterol concentrations in obese Zucker fa/fa rats fed diets with 25% of total dietary protein from rest raw material of herring hydrolysate [15] or 100% of total dietary protein from salmon hydrolysate [12]. In contrast to this, no effects on serum cholesterol concentrations were seen after intake of a diet with 25% of total protein from salmon hydrolysate from rest raw material [15] or 25% of total protein from cod protein [27] in obese Zucker fa/fa rats. These diverging results underline the need for further research on the effects of different fish proteins and peptides on cholesterol metabolism. ...
... The lipids in the diets were extracted according to the method described by Bligh and Dyer [38] using a mixture of methanol and chloroform. The fatty acid composition of the diets were analyzed by GC after lipid extraction and methylation, as described previously [27,38]. Dietary lipid extracts were evaporated to dryness using nitrogen and re-dissolved in isopropanol before quantification of total cholesterol on the Cobas c111 system (Roche Diagnostics GmbH, Marburg, Germany) using the CHOL2 (Cholesterol Gen.2) kit from Roche Diagnostics. ...
Article
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Proteins from different fish species and different raw materials such as fish fillets and by-products have shown promising cardioprotective effects in rodents and humans, including effects on cholesterol metabolism. Blue whiting is used mainly to produce fish meal for the feed industry and during this production, a water-soluble protein fraction, containing small peptides that are easily absorbed and may hold bioactive properties, is isolated. The effects of water-soluble fish protein on cholesterol metabolism were investigated in twelve male obese Zucker fa/fa rats. Rats were fed diets with water-soluble protein from blue whiting (BWW) as 1/3 of the total protein and the remaining 2/3 as casein (BWW group) or with casein as the sole protein source (control group). After 5 weeks intervention, the BWW group had lower serum total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol concentrations and lower cholesteryl ester concentration compared to controls. Hepatic concentrations of cholesterol, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and LDL receptors were also lower in the BWW group. The groups had a similar concentration of serum total bile acids and similar fecal excretions of cholesterol and bile acids. To conclude, the BWW diet led to lower concentrations of serum and liver cholesterol in obese Zucker fa/fa rats, probably due to lower hepatic cholesterol synthesis.
... The contents of total amino acids, free amino acids, taurine and total energy in the diets were analysed by Nofima BioLab (Hordaland, Norway). Lipids were extracted from diets using a mixture of chloroform and methanol [37], and fatty acid composition and cholesterol content in the diets were analysed by gas chromatography and spectrometry, respectively, as previously described [35,[37][38][39][40][41]. ...
... Serum and epididymal adipose tissue samples were methylated without prior extraction of lipids. Extracts, serum and adipose tissue were methylated and analysed as described previously [38][39][40][41]. ...
... Cholesterol was measured in lipid extracts from liver, skeletal muscle and faeces as previously described [37,41]. ...
Article
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Increasing evidence indicates that lean fish consumption may benefit cardiovascular health. High cholesterol and low n-3 PUFA concentrations in serum are associated with an increased risk of coronary heart disease; therefore, it is of interest to investigate effects of cod intake on cholesterol and n-3 PUFAs in serum and tissues. Hypercholesterolemic obese Zucker fa/fa rats were fed diets containing 25% protein from baked cod fillet and 75% protein from casein (Baked Cod Diet), or casein as the sole protein source (Control Diet) for four weeks. Consuming Baked Cod Diet resulted in lower serum cholesterol and lower hepatic mRNA concentrations of HMG-CoA reductase and sterol O-acyltransferase-2 without affecting serum bile acid concentration, faecal excretion of cholesterol and bile acid, and hepatic concentrations of bile acids, cholesterol and cholesterol 7 alpha-hydroxylase mRNA when compared to Control Diet. Rats fed Baked Cod Diet had higher concentrations of n-3 PUFAs in serum, liver, skeletal muscle and adipose tissue. To conclude, baked cod fillet intake resulted in lower serum cholesterol, which was probably caused by lower endogenous cholesterol synthesis, and higher n-3 PUFA in serum and tissues in obese Zucker fa/fa rats. These findings support the evidence that lean fish consumption might benefit cardiovascular health.
... these risk markers should be targeted as a measure to prevent disease development in overweight and obese adults. Fish consumption as part of a balanced diet has been associated with beneficial health effects [4,5], and recent studies have shown that cod intake can improve glucose regulation and insulin sensitivity in both rats and humans [6][7][8][9]. Since cod is a lean fish, these findings suggest that not only the long-chain n-3 polyunsaturated fatty acids (PUFAs) may be important in explaining positive health effects derived from fish intake, but also other nutrients such as proteins may be beneficial. ...
... Studies exploring effects on glucose regulation with cod consumption with either cod fillet intake or cod protein supplementation have come to variable conclusions depending on study design and population [6][7][8][9][12][13][14]. Intake of cod fillet has been shown to improve glucose regulation in insulin resistant individuals [7], however a high cod intake (750 g/week) seems to have little impact on glucose and insulin concentrations in normoglycemic normal-weight and overweight adults [13,14]. ...
... Intake of cod fillet has been shown to improve glucose regulation in insulin resistant individuals [7], however a high cod intake (750 g/week) seems to have little impact on glucose and insulin concentrations in normoglycemic normal-weight and overweight adults [13,14]. Isolated proteins from cod muscle, on the other hand, beneficially improved postprandial glucose concentrations in both nondiabetic humans and rats [6,8,9,12]. The decreased postprandial NEFA seen in the Cod-PC group in the current study could imply effects on glucose regulation seen together with the decrease in 2-h postprandial glucose. ...
Article
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Improved process technologies have allowed fishing vessels to utilize residuals from cod fillet production (head, backbone, skin, cuttings, and entrails) and convert this to high-quality protein powders for human consumption. In this double-blind pilot study, 42 healthy overweight or obese adults were randomized to three experimental groups consuming tablets corresponding to 6 g/day of proteins from cod residuals as presscake meal (Cod-PC), presscake and stickwater meal (Cod-PCW), or placebo tablets (control) for eight weeks. The primary outcome of this study was changes in metabolites related to glucose regulation in overweight or obese healthy adults after intake of proteins from cod residuals. Cod-PC supplementation decreased postprandial serum nonesterified fatty acids (NEFA) concentration and increased gene expressions of diglyceride acyltransferase 1 and 2 in subcutaneous adipose tissue compared with controls. Fasting insulin increased while fasting NEFA and 120-min postprandial glucose decreased within the Cod-PC group, but these changes did not differ from the other groups. In conclusion, supplementation with Cod-PC beneficially affected postprandial serum NEFA concentration compared with the other groups in overweight or obese adults. Supplementation with Cod-PCW, which contains a higher fraction of water-soluble protein compared to Cod-PC, did not affect serum markers of glucose regulation.
... Further, cod fillet intake has showed a tendency to reduce nonesterified fatty acid (NEFA) concentrations in normal-weight adults (12). Cholesterol and NEFA lowering effects have also been demonstrated in obese rats that were fed diets containing proteins from cod fillet (13)(14)(15)(16). Both the cod fillet and residuals from cod fillet production (head, backbone, skin, cut-offs, and entrails) contain high quality proteins (17). ...
... Reduced serum NEFA concentration and increased gene expressions of the lipogenic enzymes diacylglyceride acyltransferase types 1 and 2 in subcutaneous adipose tissue biopsies have been observed after cod residual protein intake in overweight or obese adults (18), thus suggesting that lower serum NEFA concentration in the current study could be a consequence of inhibition of NEFA release from adipose tissue. In line with this, lower NEFA concentration has also been observed when obese Zucker fa/fa rats were fed cod protein as 25% of their daily protein intake (14). Thus, a lowering effect of cod proteins on serum NEFA concentration seems to be a consistent finding and may be part of the beneficial effects on CVD risk markers associated with lean fish consumption (24,25). ...
... This may suggest that a high frequency of cod protein intake in the supplement studies with three doses per day, as opposed to a lower frequency with five cod fillet portions per week, may have more potent effects on lipid metabolism. This is also supported by rat studies where lower serum lipid concentrations were observed in obese Zucker rats with free access to cod protein 24 h/day (14,16). A frequent cod protein intake may have contributed to maintaining a steady state where amino acids or other compounds in the cod protein could lead to a more constant influence on lipid metabolism. ...
Article
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Background Fish fillet consumption is associated with beneficial health effects; however, little is known about whether consuming other parts of the fish such as head, backbone, skin, cut-offs, and entrails (collectively known as residuals) will provide comparable effects. Objective The aim of the study was to investigate if daily supplementation with cod residual protein powder would impact lipid metabolism in healthy adults. Methods Forty healthy, lean, physically active participants (18 women, 22 men) with normal body mass index consumed 8.1 g of proteins daily from cod residual protein powder (Cod-RP) or placebo (control) for 8 weeks. Results Cod residual protein powder supplementation lowered fasting serum nonesterified fatty acids and increased serum total bile acid concentrations significantly when compared with control supplementation. Fasting serum low-density lipoprotein cholesterol and apolipoprotein (Apo) B concentrations, as well as the total cholesterol:high-density lipoprotein (HDL) cholesterol and ApoB:ApoA1 ratios, were significantly decreased within the Cod-RP group, but these changes were not different from the control group. Fasting serum concentrations of triacylglycerol, total cholesterol, HDL cholesterol, and ApoA1 were not changed within or between groups. Conclusion Eight weeks of daily supplementation with 8.1 g Cod-RP seems to be sufficient to affect lipid metabolism in healthy, lean, physically active adults.
... Rat studies suggest that proteins from various fish species exert different physiological effects such as improved insulin sensitivity or glucose tolerance [16][17][18][19], and reduced circulating concentrations of lipids [18,20,21]. Recently, we showed that in obese Zucker fa/fa rats, both salmon hydrolysate and cod protein feeding resulted in lower postprandial glucose concentration, herring hydrolysate feeding resulted in lower serum concentrations of HDL and LDL cholesterols, cod protein feeding resulted in lower serum fasting NEFA concentration, and rats fed proteins from herring or cod had higher ratio of n-3 to n-6 PUFA in serum when compared to casein-whey mixture [22,23]. Results from these rat studies encouraged investigation of the same proteins in a clinical trial. ...
... In the present study we investigated the effects of fish and milk proteins from the same production batches that were tested in obese Zucker fa/fa rats [22,23]. Since we have previously shown that a daily dose of 6 g of cod protein improved glucose metabolism and lowered LDL cholesterol concentration in overweight and obese adults [24], we now wanted to test the potency of a lower daily dose of fish proteins. ...
... The amino acids derivatives were separated by reverse phase HPLC in a Waters 2695 Separation Unit, and read in a Waters 2475 Multi Florescence Detector with excitation at 250 nm and emission at 395 nm. Fatty acids in tablets were extracted by the method described by Bligh and Dyer [29] and methylated and analysed as described previously [22,[30][31][32]. The fish protein hydrolysates were difficult to compress into the tablets due to their fluffy texture, therefore, the protein content in HER and SAL tablets were 50% lower compared to that of COD and CAS tablets. ...
Article
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Purpose To examine whether supplementation with low doses of fish or milk proteins would affect glucose regulation and circulating lipid concentrations in overweight healthy adults. Methods Ninety-three overweight adults were assigned to receive 2.5 g protein/day from herring (HER), salmon (SAL), cod (COD) or milk (CAS, a casein–whey mixture as positive control) as tablets for 8 weeks. Results Seventy-seven participants were included in the analyses. HER and SAL did not affect glucose and insulin concentrations. COD significantly reduced within-group changes in 90 and 120 min postprandial glucose concentrations but changes were not different from HER and SAL groups. CAS supplementation significantly reduced the area under the curve for glucose concentrations (− 7%), especially when compared to SAL group, and reduced postprandial insulin c-peptide concentration (− 23%). Reductions in acetoacetate (− 24%) and β-hydroxybutyrate (− 29%) serum concentrations in HER group were more prominent compared to SAL and COD groups, with no differences between fish protein groups for α-hydroxybutyrate. Serum concentrations of α-hydroxybutyrate (− 23%), acetoacetate (− 39%) and β-hydroxybutyrate (− 40%) were significantly reduced within CAS group, and the decreases were significantly more pronounced when compared to SAL group. Serum lipid concentrations were not altered in any of the intervention groups. Conclusion Findings indicate that 2.5 g/day of proteins from fish or milk may be sufficient to improve glucose regulation in overweight adults. The effects were most pronounced after supplementation with proteins from cod, herring and milk, whereas salmon protein did not affect any of the measurements related to glucose regulation. Clinical trail registration This trial was registered at clinicaltrials.gov as NCT01641055.
... Previous studies in rats and human subjects have shown that the intake of both fish proteins and marine protein hydrolysates (MPH), even in low doses, has a desirable effect on insulin sensitivity and postprandial glucose (7,(15)(16)(17)(18)(19) , lipids in serum and adipose tissue, bile acids, fatty acid composition and growth, and possibly has antihypertensive and immunemodulating effects (14,(19)(20)(21)(22)(23) . It is indicated that MPH may contain marine bioactive compounds with potentially important biological effects in humans, beyond the known effect of protein as a source of amino acids (24,25) . ...
... Previous studies in rats and human subjects have shown that the intake of both fish proteins and marine protein hydrolysates (MPH), even in low doses, has a desirable effect on insulin sensitivity and postprandial glucose (7,(15)(16)(17)(18)(19) , lipids in serum and adipose tissue, bile acids, fatty acid composition and growth, and possibly has antihypertensive and immunemodulating effects (14,(19)(20)(21)(22)(23) . It is indicated that MPH may contain marine bioactive compounds with potentially important biological effects in humans, beyond the known effect of protein as a source of amino acids (24,25) . ...
Article
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The increased prevalence of lifestyle diseases, such as the metabolic syndrome and type 2 diabetes mellitus (T2DM), calls for more knowledge on dietary treatments targeting the specific metabolic pathways involved in these conditions. Several studies have shown a protein preload before a meal to be effective in lowering the postprandial glycaemic response in healthy individuals and patients with T2DM. The aim of the present study was to assess the effect of a marine protein hydrolysate (MPH) from Atlantic cod ( Gadus morhua ) on postprandial glucose metabolism in healthy, middle-aged to elderly subjects. This double-blind cross-over trial ( n 41) included two study days with 4–7 d wash-out in between. The intervention consisted of 20 mg of MPH (or casein as control) per kg body weight given before a breakfast meal. The primary outcome was postprandial response in glucose metabolism, measured by samples of serum glucose, insulin and plasma glucagon-like peptide 1 (GLP-1) in 20 min intervals for 180 min. In a mixed-model regression analysis, no differences were observed between MPH and control for postprandial glucose concentration (mean difference: −0·04 (95 % CI –0·17, 0·09) mmol/l; P = 0·573) or GLP-1 concentration (mean difference between geometric means: 1·02 (95 % CI 0·99, 1·06) pmol/l; P = 0·250). The postprandial insulin concentration was significantly lower after MPH compared with control (mean difference between geometric means: 1·067 (95 % CI 1·01, 1·13) mIU/l; P = 0·032). Our findings demonstrate that a single dose of MPH before a breakfast meal reduces postprandial insulin secretion, without affecting blood glucose response or GLP-1 levels, in healthy individuals. Further studies with repeated dosing and in target groups with abnormal glucose control are warranted.
... The dietary contents of amino acids, total fat (Folch extraction) and total energy in the diets were analyzed by Nofima BioLab (Bergen, Norway), and the fatty acid composition in the diets were analyzed by gas chromatography as previously described [31][32][33][34][35], and have been published earlier [26]. In brief, the dietary contents of indispensable amino acids were in general similar in Control Diet and Baked Salmon Diet, whereas taurine was found only in the Baked Salmon Diet. ...
... Lipids were extracted from serum by the method of Bligh and Dyer [31] using a mixture of chloroform and methanol, and lipid classes were separated by TLC on silica gel plates (250 µm Silica gel 60 from Merck KGaA, Darmstadt, Germany) developed in hexane-diethyl ether-acetic acid (40:10:1, by vol) [36]. The triacylglycerols and phospholipids spots were identified using Rhodamine G (Fluka Chemie AG, Buchs, Switzerland) and co-migration with known standards, and were scraped off, methylated and analyzed as described previously [32][33][34][35]. ...
Article
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The triacylglycerol lowering effect of fatty fish and fish oils is well recognized, however we recently showed that salmon intake resulted in higher serum triacylglycerol concentration in obese Zucker fa/fa rats. Since effects of salmon fillet have never before been studied in rats, the objective of this study was to compare effects of salmon intake on serum lipids in hyperlipidemic obese rats with normolipidemic lean rats. Zucker fa/fa rats and Long-Evans rats were fed diets with 25% protein from baked salmon fillet and 75% protein from casein, or casein as sole protein source (control group) for four weeks. Serum triacylglycerol concentration was higher, and cholesterol and apolipoproteinB-100 concentrations were lower in Zucker fa/fa rats fed Baked Salmon Diet compared to Zucker fa/fa rats fed Control Diet, with no differences in serum triacylglycerol, cholesterol and apolipoproteinB-100 between Long-Evans rats fed Baked Salmon Diet or Control Diet. Serum triacylglycerol fatty acid composition showed greater similarities to dietary fatty acids in Zucker fa/fa rats than in Long-Evans rats. To conclude, intake of baked salmon fillet resulted in higher serum triacylglycerol concentration and lower serum cholesterol concentration in hyperlipidemic obese Zucker fa/fa rats but did not affect serum lipids in normolipidemic lean Long-Evans rats.
... In diabetic patients, this effect was ascribed to the protein component of the fish [23]. We have recently shown that fish proteins improve glucose regulation in obese Zucker fa/fa rats [15,24], and since poor glycemic control increases the risk of developing kidney damage, we believe that it is of great interest to investigate the effects of fish proteins on kidney function. Obesity is associated with proteinuria and focal segmental glomerulosclerosis both in humans and rats, and increases the risk of developing renal disease [1][2][3][4]13]. ...
... Therefore, no power analysis has been conducted for the present study. Fish protein hydrolysates were added to the diets in amounts corresponding to 25% of the total dietary protein, which is about two-fold higher than the recommended intake of protein from fish for healthy adults [24], however, in most published rat studies on fish protein diets to date, fish protein has been given as 100% of protein source [40][41][42][43][44][45][46][47][48][49][50] or 50% combined with 50% casein [51][52][53][54]. Kidney tissues from the rats were not fixated therefore a limitation to our study is the lack of histopathological data from the kidneys, and we did not measure creatinine clearance or glomerular filtration rate. ...
Article
The use of angiotensin-I converting enzyme (ACE) inhibitors is a common strategy for treating kidney disease. Several amino acids sequences with ACE inhibiting activity are identified in filet and rest raw material from various species of fish, and fish protein hydrolysates could be of interest for possible treatment or prevention of kidney disease. Therefore, we hypothesized that protein hydrolysates from rest raw material from herring and salmon containing ACE inhibiting motifs could beneficially affect typical markers for kidney function in an obesity rat model prone to developing renal failure. We identified 81 and 49 peptide sequences with known ACE inhibiting activity in herring and salmon protein hydrolysates from rest raw material. To investigate the effects of fish protein hydrolysates on markers of kidney function, obese Zucker fa/fa rats consumed diets with 25% of protein from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material and 75% of protein from casein/whey, or 100% protein from casein/whey (CAS) for 4 weeks. Rats fed HER or SAL diets had lower urine concentrations (relative to creatinine) of protein, cystatin C and glucose when compared to rats fed CAS diets. No differences were found between diet groups for serum concentrations of protein, creatinine and cystatin C. Protein hydrolysates from herring and salmon rest raw material contained several peptide sequences with known ACE inhibiting activities, and resulted in lower urine concentrations of proteins, cystatin C and glucose when fed to obese Zucker rats.
... Studies suggests that there are other components in fish such as fish proteins that may be beneficial to human health and affect risk factors leading to CVD, beyond n-3 fatty acids (15)(16)(17)(18) . This is supported by results from animal studies showing that fish proteins may have a lowering effect on TAG and cholesterol as well as improve glucose tolerance (19)(20)(21)(22)(23)(24)(25)(26) . In line with this, we have recently shown that supplementation with cod protein as tablets reduced fasting glucose and LDL-cholesterol as well as postprandial glucose concentrations in healthy, overweight adults (17) . ...
... There is controversy about the glucose-regulating effects of fatty fish or fish oil (9)(10)(11)31,35,48) ; however, studies in rats that are obese and/or fed high-fat or high-carbohydrate diets suggest that intake of fish proteins may improve glucose tolerance (21)(22)(23)(24)26) . Clinical studies also suggest that fish proteins may improve glucose regulation in overweight/obese participants (17)(18) . ...
Article
The prevalence of type 2 diabetes (T2D) is low in populations with a high fish intake; however prospective studies with fish intake have shown positive, negative or no association between fish intake and the risk for T2D. The aim of this study was to investigate the effects of high intake of lean or fatty fish on glucose tolerance, leucocyte membrane fatty acid composition and leucocyte function in overweight/obese adults. In this randomised clinical trial, sixty-eight healthy overweight/obese participants consumed 750 g/week of either lean or fatty fish as dinners, or were instructed to continue their normal eating habits but to avoid fish intake (control group), for 8 weeks. Energy and macronutrient intake and physical activity were not changed within the groups during the study period. High intake of fatty fish, but not of lean fish, significantly improved glucose regulation 120 min postprandially ( P =0·012), but did not affect fasting glucose concentration. A smaller increase in fasting to 120 min postprandial insulin C-peptide concentration was seen after fatty fish intake ( P =0·012). Lean fish increased the DHA content in leucocyte membranes ( P =0·010), and fatty fish increased the total content of n -3 PUFA ( P =0·00016) and reduced the content of n -6 PUFA ( P =0·00057) in leucocyte membranes. Lean and fatty fish intake did not affect phagocytosis of bacteria ex vivo . The findings suggest that high intake of fatty fish, but not of lean fish, beneficially affected postprandial glucose regulation in overweight/obese adults, and may therefore prevent or delay the development of T2D in this population.
... The rats develop obesity a few weeks after birth and develop obesityrelated comorbidities such as dyslipidemia and fatty liver [19]. Previous studies from our lab with diets containing 25% of protein from fish show that proteins from different fish species, i.e. cod, herring and salmon, affect growth, glucose regulation and lipid metabolism in obese Zucker fa/fa rats [20,21]. In the present study we investigated the effects of diets containing the same amount of protein from baked or raw salmon fillet. ...
... In the present study, serum TAG were significantly higher in rats fed baked salmon (p = 0.015) and tended to be higher (p = 0.067) in rats fed raw salmon compared to control fed rats, with no differences in hepatic TAG levels between the groups. Previously, we have observed no effects on serum TAG with diets containing 25% of protein from cod or salmon [20,21] and higher serum TAG with diet containing 25% of protein from herring [21] in Zucker fa/fa rats. This indicates that consumption of different types of fish protein as well as fish fillet may affect serum TAG in obese rats. ...
Article
Knowledge of the health impact of consuming heat-treated versus raw fish fillet is limited. To investigate effects of baked or raw salmon fillet intake on lipids and n-3 PUFAs in serum and tissues, obese Zucker fa/fa rats were fed diets containing 25% of protein from baked or raw salmon fillet and 75% of protein from casein, or casein as the sole protein source (control group) for four weeks. Salmon diets had similar composition of amino and fatty acids. Growth and energy intake were similar in all groups. Amounts of lipids and n-3 PUFAs in serum, liver and skeletal muscle were similar between rats fed baked or raw salmon fillet. When compared to the control group, rats fed baked salmon had lower serum total and LDL cholesterol and higher serum triacylglycerol levels. Both raw and baked salmon groups had lower HDL cholesterol level when compared to control rats. In conclusion, baking as a preparation method does not alter protein and fat qualities of salmon fillets, and intake of baked and raw salmon fillets gave similar effects on lipids and n-3 PUFAs in serum and tissues from rats.
... Fish intake is associated with beneficial effects on risk factors for type 2 diabetes and cardiovascular disease [1][2][3][4][5][6][7], and these effects have mainly been attributed to the content of longchain n-3 polyunsaturated fatty acids (n-3 PUFA) in fish [8]. Although underlying mechanisms are still unclear, several studies have shown that lean fish may also improve insulin sensitivity and glucose regulation, despite containing very low amounts of long-chain n-3 PUFA [9][10][11][12][13][14][15]. Small alterations in glucose regulation may be difficult to identify in short-term dietary intervention studies among healthy individuals. ...
... The current study also demonstrates decreased glucose concentration 60 min after glucose intake in the Cod-RP group, from baseline to eight weeks, compared with the Control group, however, postprandial measurements 30, 90 and 120 min did not differ between the two groups. Previous studies have observed that intake of proteins from cod fillet or cod residuals may improve postprandial glucose regulation in overweight adults and in obese rats, with no effects on fasting serum concentrations of glucose or insulin [12][13][14]38]. In line with this, two clinical studies, investigating the effects of 750 g cod fillet per week in normal-weight adults for four weeks [39], or overweight adults for eight weeks [40], did not find beneficial effects on fasting glucose and insulin concentrations. ...
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Large quantities of protein-rich cod residuals, which are currently discarded, could be utilized for human consumption. Although fish fillet intake is related to beneficial health effects, little is known about the potential health effects of consuming cod residual protein powder. Fifty lean adults were randomized to consume capsules with 8.1 g/day of cod residual protein (Cod-RP) or placebo capsules (Control group) for eight weeks, in this randomized, double-blind study. The intervention was completed by 40 participants. Fasting glucose and insulin concentrations were unaffected by Cod-RP supplementation, whereas plasma concentrations of α-hydroxybutyrate, β-hydroxybutyrate and acetoacetate all were decreased compared with the Control group. Trimethylamine N-oxide concentration in plasma and urine were increased in the Cod-RP group compared with the Control group. To conclude, the reduction in these potential early markers of impaired glucose metabolism following Cod-RP supplementation may indicate beneficial glucoregulatory effects of cod residual proteins. Trimethylamine N-oxide appears to be an appropriate biomarker of cod residual protein intake in lean adults.
... Studies suggests that there are other components in fish such as fish proteins that may be beneficial to human health and affect risk factors leading to CVD, beyond n-3 fatty acids (15)(16)(17)(18) . This is supported by results from animal studies showing that fish proteins may have a lowering effect on TAG and cholesterol as well as improve glucose tolerance (19)(20)(21)(22)(23)(24)(25)(26) . In line with this, we have recently shown that supplementation with cod protein as tablets reduced fasting glucose and LDL-cholesterol as well as postprandial glucose concentrations in healthy, overweight adults (17) . ...
... There is controversy about the glucose-regulating effects of fatty fish or fish oil (9)(10)(11)31,35,48) ; however, studies in rats that are obese and/or fed high-fat or high-carbohydrate diets suggest that intake of fish proteins may improve glucose tolerance (21)(22)(23)(24)26) . Clinical studies also suggest that fish proteins may improve glucose regulation in overweight/obese participants (17)(18) . ...
Article
The aim of the present study was to examine whether high intake of lean or fatty fish (cod and farmed salmon, respectively) by healthy, normal-weight adults would affect risk factors of type 2 diabetes and CVD when compared with lean meat (chicken). More knowledge is needed concerning the potential health effects of high fish intake (>300 g/week) in normal-weight adults. In this randomised clinical trial, thirty-eight young, healthy, normal-weight participants consumed 750 g/week of lean or fatty fish or lean meat (as control) for 4 weeks at dinner according to provided recipes to ensure similar ways of preparations and choices of side dishes between the groups. Energy and macronutrient intakes at baseline and end point were similar in all groups, and there were no changes in energy and macronutrient intakes within any of the groups during the course of the study. High intake of fatty fish, but not lean fish, significantly reduced TAG and increased HDL-cholesterol concentrations in fasting serum when compared with lean meat intake. When compared with lean fish intake, fatty fish intake increased serum HDL-cholesterol. No differences were observed between lean fish, fatty fish and lean meat groups regarding fasting and postprandial glucose regulation. These findings suggest that high intake of fatty fish, but not of lean fish, could beneficially affect serum concentrations of TAG and HDL-cholesterol, which are CVD risk factors, in healthy, normal-weight adults, when compared with high intake of lean meat.
... Nutritional interventions have focused on providing optimal amounts of nutrients including proteins, but little is known about whether altering the type of dietary proteins could beneficially affect the development of age-related loss of muscle mass and function in older adults. In rats, fish protein feeding has been shown to beneficially affect fasting [13,14] and postprandial [15][16][17] glucose concentrations. Clinical studies show lower fasting and postprandial glucose concentrations in overweight or obese adults after fish protein intake [18] and improved insulin sensitivity in insulin-resistant adults after lean fish intake [19]. ...
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Background Age-related loss of muscle mass and function is common in older adults, and studies investigating if dietary proteins may protect and possibly build lean body mass are needed. We assessed the feasibility of conducting a nutritional intervention study in older nursing home residents to investigate the effects of fish protein supplementation on markers of glucose metabolism and inflammation. Methods This was a double-blind randomised controlled pilot study. Twenty-four nursing home residents, without major cognitive impairment, received a daily oral nutritional supplement containing 5.2 g of fish protein or placebo for 6 weeks. Anthropometric measurements were conducted at baseline. Participants were screened for nutritional risk using the Mini Nutritional Assessment and activities of daily living using the Barthel index and dietary intake was registered. Hand grip strength was measured and fasting blood samples collected at baseline and endpoint. Results Compliance was high and dropout was low, but participant recruitment was challenging. Serum concentrations of monocyte chemoattractant protein-1 decreased, and C-reactive protein increased in the intervention group compared to control, with no changes in markers of glucose metabolism between groups. Conclusion Conducting a nutritional intervention using fish protein supplementation in older nursing home residents is feasible but should be conducted as a multi-centre study to account for the low recruitment rate observed in the present study. A full-scale study is needed to gain more knowledge on the potential effects of fish proteins on markers of glucose metabolism and inflammation in relation to the age-related loss of muscle mass and function. Trial registration ClinicalTrials.gov NCT03529344 18.05.2018 (retrospectively registered)
... Cholesterol was measured in lipid extracts from faeces as previously described [34,35] using the Cholesterol Gen.2 kit for Cobas c111 from Roche Diagnostics GmbH (Mannheim, Germany). Total bile acids (3α-hydroxy bile acids) concentration was measured in freeze-dried faeces after solid phase extraction with Chromabond C18 ec (3 ml/200 mg, Macherey-Nagel, Düren, Germany) as described by Suckling et al. [36] and quantification using the enzymatic bile acid assay from Diazyme Laboratories, Inc. on the Cobas c111 system (Roche). ...
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Purpose To explore whether high intake of cod or salmon would affect gut microbiota profile, faecal output and serum concentrations of lipids and bile acids. Methods Seventy-six adults with overweight/obesity with no reported gastrointestinal disease were randomly assigned to consume 750 g/week of either cod or salmon, or to avoid fish intake (Control group) for 8 weeks. Fifteen participants from each group were randomly selected for 72 h faeces collection at baseline and end point for gut microbiota profile analyses using 54 bacterial DNA probes. Food intake was registered, and fasting serum and morning urine were collected at baseline and end point. Results Sixty-five participants were included in serum and urine analyses, and gut microbiota profile was analysed for 33 participants. Principal component analysis of gut microbiota showed an almost complete separation of the Salmon group from the Control group, with lower counts for bacteria in the Bacteroidetes phylum and the Clostridiales order of the Firmicutes phyla, and higher counts for bacteria in the Selenomonadales order of the Firmicutes phylum. The Cod group showed greater similarity to the Salmon group than to the Control group. Intake of fibres, proteins, fats and carbohydrates, faecal daily mass and output of fat, cholesterol and total bile acids, and serum concentrations of cholesterol, triacylglycerols, non-esterified fatty acids and total bile acids were not altered in the experimental groups. Conclusion A high intake of cod or salmon fillet modulated gut microbiota but did not affect faecal output or serum concentrations of lipids and total bile acids. Clinical trial registration This trial was registered at clinicaltrials.gov as NCT02350595.
... Serum and WATepi were methylated without prior extraction of lipids. Fatty acids in liver and diet extracts, serum and WATepi were analysed by gas chromatography as described previously [39]. ...
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PurposeTo investigate the effects of diets containing intact or hydrolysed proteins from blue whiting (Micromesistius poutassou) on the development of high blood pressure and markers of kidney function in obese Zucker fa/fa rats which are prone to develop hypertension and renal failure.Methods Male rats were fed isocaloric diets containing either intact blue whiting whole meal (BW-WM), blue whiting protein hydrolysate prepared with Alcalase® (BW-HA) or blue whiting protein hydrolysate prepared with Protamex® (BW-HP) as 1/3 of total protein with the remaining 2/3 as casein, or casein as sole protein source (control group). Blood pressure was measured at Day 0 and Day 32. Rats were housed in metabolic cages for 24 h for collection of urine in week 4. After 5 weeks, rats were euthanized and blood was drawn from the heart. The renin and angiotensin-converting enzyme (ACE) inhibition capacities for casein and blue whiting proteins were measured in vitro.ResultsThe blood pressure increase was lower in rats fed diets containing blue whiting proteins when compared to the control group, whereas markers of kidney function were similar between all groups. The three blue whiting proteins inhibited renin activity in vitro, whereas casein had no effect. The in vitro ACE inhibition was similar for casein, BW-WM and BW-HP proteins, whereas BW-HA protein was less potent.Conclusion Blue whiting protein feeding attenuated the blood pressure increase in obese Zucker fa/fa rats, possibly mediated through the renin–angiotensin system and without affecting markers of kidney function.
... In the more recent research, a decreased risk of metabolic syndrome in adults has been attributed to the consumption of lean fish (Torris et al., 2016). Drotningsvik et al. (2015) indicated that already a low dietary intake of cod protein (25%) compared to a casein only diet, improved lipid metabolism and glucose regulation in obese rats. For humans, Aadland et al. (2015) showed that already 4 weeks of a diet with 60% of proteins from lean-seafood reduced serum triacylglycerol concentrations and prevented elevation in VLDL particle number in comparison to a diet without seafood-proteins. ...
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The present review aims to give a concise review about important nutrients from fish and their impact on human health. In addition, possible effects of rearing system and feeding on the most vulnerable group of nutrients, the lipids, are summarized. Fish are considered as nutritionally valuable part of the human diet and consumption two times a week is recommended, mostly due to the content of long chain polyunsaturated n-3 fatty acids. These fatty acids are essential in human nutrition and have proven to be involved in many metabolic functions. Among others, they have anti-inflammatory effects, decrease platelet aggregation and are essential parts in the cell membranes, cardiovascular system, brain, and nervous tissue. In addition the proteins, peptides and amino acids from fish became more recently known for having positive health effects. Furthermore fish is also a rich source of certain vitamins and minerals as Vitamin D, selenium, phosphorus, and calcium. It should be highlighted that, when considering nutrition and related health aspects, it is impossible to focus one group of nutrients separately. Most probably the discussed effects of fish on human health are due to the consumption of the fish as a whole and hence the combination of all present nutrients.
... Interestingly, we previously reported that fish consumption once a week or more was significantly associated with higher TG in women and a lower TG in men, when investigating fatty and lean fish together [21]. Cod protein has been associated with beneficial effects on lipid metabolism in rats [56], and beneficial effects of taurine on lipid profiles have also been suggested [39,40,57]. Dietary proteins have been found to slow both the absorption and synthesis of lipids, and to promote lipid excretion [58]. ...
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Background: Fish consumption may have beneficial effects on metabolic syndrome (MetS); however, limited information of such associations exists. This study investigated possible associations between fish consumption and changes in MetS components during a 13-year follow-up period. Methods: The sample included participants (26–69 years) from the Tromsø Study 4 (1994–1995, n = 23,907) and Tromsø Study 6 (2007–2008, n = 12,981). Data were collected using questionnaires including food frequency questions, non-fasting blood samples, and physical examinations. MetS was defined using the Joint Interim Societies (JIS) definition, in which one point was given for each MetS criteria fulfilled (metabolic score). Longitudinal analyses were performed using Linear mixed models. Results: For both genders, lean fish consumption once a week or more was significantly associated with decreased future metabolic score, decreased triglycerides, and increased high-density lipoprotein (HDL)-cholesterol, whereas decreased waist circumference and blood pressure was identified only for men (age adjusted models). Fatty fish consumption was significantly associated with increased waist circumference for both genders and increased HDL-cholesterol levels in men. Conclusion: The results suggest that fatty and lean fish consumption may influence MetS differently and that lean fish consumption in particular seems to be associated with beneficial changes in the MetS components.
... [1] They play a vital role in tissue maintenance and body functions, as well as being essential components in the cells of the muscles, bones, organs, tendons, and ligaments. [2] In particular, peptides, which are protein hydrolysates obtained mainly by enzymatic proteolysis of proteins from various food sources, have aroused considerable attentions due to their unique bioactive natures. Increasing researches demonstrate that these peptides possess multibiological functions including antioxidant, antimicrobial, hypotensive, anticoagulant, and cholesterol-lowering ability, [3] and have potentials in cancer targeting labelling and identification diagnosis. ...
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The degree of hydrolysis (DH) is one of the most important indexes for process control and quality assessment in proteins enzymatic hydrolysis. This paper proposed a simple and rapid near infrared (NIR) spectroscopy method for real-time quantifying the DH in alcalase hydrolysis process. Efficient variables selection algorithms were systemically studied in multivariate calibrations; the partial least squares (PLS) coupled with uninformative variables elimination (UVE) and ant colony optimization (ACO), namely UVE-ACO-PLS, were proposed for modeling with results yielding Rp = 0.9525. Additionally, 10 independent samples with the relative error (RE) less than 10% further confirmed the stability and reliability of this method. This work demonstrated that the NIR spectroscopy technique with a selected multivariate calibration has a high potential for in situ monitoring of alcalase hydrolysis process in protein industry.
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Peony seed oil (PSO) is a new resource food rich in α-Linolenic Acid(ALA) (38.66%). The objective of this study was to assess the modulatory effect of PSO on lipid metabolism. Lard oil, safflower oil (SFO), and PSO were fed to wistar rats with 1% cholesterol in the diet for 60 d. Serum and liver lipids showed significant decrease in total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C) levels in PSO fed rats compared to lard oil and SFO fed rats. ALA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), contents were significantly increased, whereas linoleic acid (LA), arachidonic acid (AA) levels decreased in serum and liver of PSO fed rats. Feeding PSO increased ALA level and decreased n-6 to n-3 polyunsaturated fatty acid (PUFA) ratio. The hypolipidemic result of PSO indicated that PSO participated in the regulation of plasma lipid concentration and cholesterol metabolism in liver. The decreased expression of sterol regulatory element-binding proteins 1C (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS)-reduced lipid synthesis; Activation of peroxisome proliferator-activator receptor (PPARα) accompanied by increase of uncoupling protein2 (UP2) and acyl-CoA oxidase (AOX) stimulated lipid metabolism and exerted an antiobesity effect via increasing energy expenditure for prevention of obesity.
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We have shown that feeding cod protein, which is rich in anti-inflammatory arginine, glycine, and taurine, may beneficially modulate the inflammatory response during recovery following skeletal muscle injury; however it is unknown if these amino acids are responsible for this effect. This study was designed to assess whether supplementing casein with an amino acid mixture composed of arginine, glycine, taurine and lysine, matching their respective levels in cod protein, may account for the anti-inflammatory effect of cod protein. Male Wistar rats were fed isoenergetic diets containing either casein, cod protein, or casein supplemented with L-arginine (0.45%), glycine (0.43%), L-taurine (0.17%) and L-lysine (0.44%) (casein+). After 21 days of ad libitum feeding, one tibialis anterior muscle was injured with 200 µl bupivacaine while the saline-injected contra-lateral tibialis anterior was served as sham. Cod protein and casein+ similarly modulated the inflammation as they decreased COX-2 level at day 2 post-injury (cod protein, p=0.014; casein+, p=0.029) and ED1(+) macrophage density at days 2 (cod protein, p=0.012; casein+, p
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This study examined the effects of fish protein in combination with fish oil on rat lipid metabolism. Male Wistar rats were divided into four groups and fed an AIN93G-based diet with casein (20%) + soybean oil (7%), casein (10%) + fish protein (10%) + soybean oil (7%), casein (20%) + soybean oil (5%) + fish oil (2%), and casein (10%) + fish protein (10%) + soybean oil (5%) + fish oil (2%) for 4 weeks. The dietary combination of fish protein and fish oil decreased the contents of serum triacylglycerol, serum cholesterol, liver triacylglycerol and liver cholesterol in addition to altering liver lipid fatty acid composition. These effects are partly due to the increase in fecal cholesterol, bile acid excretion, and increased enzyme activities of fatty acid β-oxidation in the liver. These data suggest that combined intake of fish protein and fish oil lead to both hypocholesterolemic and hypotriglyceridemic in serum and the liver, while sole intake of fish protein or fish oil decrease only cholesterol and triglyceride levels, respectively. These results suggest that combined intake of fish protein and fish oil may play beneficial roles in the prevention of lifestyle-related diseases as compared with sole fish protein intake.
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The popularity of high-protein diets for weight reduction is immense. However, the potential benefits from altering the source of dietary protein rather than the amount is scarcely investigated. In the present study, we examined the effects of fish protein supplement on glucose and lipid metabolism in overweight adults. A total of thirty-four overweight adults were randomised to 8 weeks' supplementation with fish protein or placebo tablets (controls). The intake of fish protein supplement was 3 g/d for the first 4 weeks and 6 g/d for the last 4 weeks. In this study, 8 weeks of fish protein supplementation resulted in lower values of fasting glucose (P < 0·05), 2 h postprandial glucose (P < 0·05) and glucose-area under the curve (AUC) (five measurements over 2 h, P < 0·05) after fish protein supplementation compared to controls. Glucose-AUC was decreased after 8 weeks with fish protein supplement compared to baseline (P < 0·05), concomitant with increased 30 min and decreased 90 min and 2 h insulin C-peptide level (P < 0·05), and reduced LDL-cholesterol (P < 0·05). Body muscle % was increased (P < 0·05) and body fat % was reduced (P < 0·05) after 4 weeks' supplementation. Physical activity and energy and macronutrients intake did not change during the course of the study. In conclusion, short-term daily supplementation with a low dose of fish protein may have beneficial effects on blood levels of glucose and LDL-cholesterol as well as glucose tolerance and body composition in overweight adults. The long-term effects of fish protein supplementation is of interest in the context of using more fish as a protein source in the diet, and the effects of inclusion of fish in the diet of individuals with low glucose tolerance should be evaluated.
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The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective strategy against insulin resistance and related situations.
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The purpose of the present study was to investigate whether water-insoluble fish protein (IFP) from Alaska pollock (Theragra chalcogramma) prevents hypercholesterolaemia induced by ovarian hormone deficiency. Wistar female rats, aged 6 months, were subjected to sham-operation or ovariectomy, and fed a cholesterol-free diet containing casein or IPF as a protein source for 28 d. Body-weight gain and food intake increased in the ovariectomised rats as compared with the sham-operated rats. Plasma total cholesterol concentration was decreased and faecal bile acid excretion was increased by IFP in the ovariectomised rats, but not in the sham-operated rats. Plasma homocysteine concentration was decreased by IFP in the ovariectomised rats, but not in the sham-operated rats. Liver lipids and liver cholesterol concentrations were increased and cholesterol 7alpha-hydroxylase (CYP7A1) activity was decreased by ovariectomy, but not by diet. Bile acid content and the ratio of cholic acid groups to chenodeoxycholic acid groups in bile were increased by ovariectomy, but decreased by IFP. Bile acid content in the small intestine was increased by IFP in the ovariectomised rats, but not in the sham-operated rats. 3-Hydroxy-3-methylglutaryl-CoA reductase and microsomal TAG transfer protein mRNA levels were decreased by ovariectomy and IFP, whereas LDL-receptor mRNA level was decreased by ovariectomy but unaffected by diet. Thus, the preventive effect of IFP on the ovarian hormone deficiency-associated increase in plasma cholesterol concentration seems to be mediated by accelerated faecal excretion of bile acids, coupled with an increase in the intestinal pool of bile acids.
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We have previously shown that bolus intravenous administration of tumor necrosis factor (TNF) to normal rats results in a rapid (within 90 min) stimulation of hepatic fatty acid synthesis, which is sustained for 17 hr. We now demonstrate that TNF stimulates fatty acid synthesis by several mechanisms. Fatty acid synthetase and acetyl-CoA carboxylase (measured after maximal stimulation by citrate) were not higher in livers from animals that had been treated with TNF 90 min before study compared to controls. In contrast, 16 hr after treatment with TNF, fatty acid synthetase was slightly elevated (35%) while acetyl-CoA carboxylase was increased by 58%. To explain the early rise in the hepatic synthesis of fatty acids, we examined the regulation of acetyl-CoA carboxylase. The acute increase in fatty acid synthesis was not due to activation of acetyl-CoA carboxylase by change in its phosphorylation state (as calculated by the ratio of activity in the absence and presence of 2 mM citrate). However, hepatic levels of citrate, an allosteric activator of acetyl-CoA carboxylase, were significantly elevated (51%) within 90 min of TNF treatment. TNF also induces an acute increase (within 90 min) in the plasma levels of free fatty acids. However, hepatic levels of fatty acyl-CoA, which can inhibit acetyl-CoA carboxylase, did not rise 90 min following TNF treatment and were 35% lower than in control livers by 16 hr after TNF. These data suggest that TNF acutely regulates hepatic fatty acid synthesis in vivo by raising hepatic levels of citrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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The effects of amount and type of dietary fish proteins on plasma and liver cholesterol concentrations were evaluated in female rats. The isonitrogenous diets used contained 10 g cholesterol/kg and were carefully balanced for residual fat, cholesterol, Ca, Mg and P in the protein preparations. Cod meal, soya-bean protein or casein was incorporated into the diets as the only source of dietary protein at three levels: either 24, 48 or 72 g N/kg diet. Extra protein was added to the diet at the expense of the glucose component. In a second experiment soya-bean protein, casein, cod meal, whiting meal or plaice meal was added to the diet at a level of 24 g N/kg. When compared with casein, cod meal and soya-bean protein decreased plasma and liver cholesterol concentrations. A further cholesterol-lowering effect was achieved by increasing the proportion of either soya-bean protein or cod meal in the diet. Substitution of casein for glucose did not influence plasma and liver cholesterol concentrations. Plaice meal in the diet produced lower group mean plasma cholesterol concentrations than did whiting meal. In rats fed on the diet containing plaice meal, liver cholesterol concentrations were significantly lower than those in their counterparts fed on either cod meal or whiting meal. The present study demonstrates that different fish proteins in the diet have different effects on cholesterol metabolism and that the cholesterol-influencing properties of cod meal can be enhanced by the incorporation of higher proportions of this protein in the diet.
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To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.
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Liver lipid content in the liver and triglyceride level in serum of growing rats were measured in the individual essential amino acid deficiencies. The basal diet contained 7% amino acid mixture. The essential amino acid level in the diet deficient in individual essential amino acids was 80% (group 2), 60% (group 3) and 40% (group 4) of that in the basal diet (group 1). Both food intake and body weight gain decreased with decreasing levels of individual essential amino acids in diet. Lipid content in the liver increased with decreasing level in threonine or lysine, and inversely decreased with decreasing level in methionine and cystine, leucine, histidine or arginine. Deficiency in other essential amino acids (phenylalanine and tyrosine, tryptophan, isoleucine and valine) had no significant effects on the lipid content in the liver. Triglyceride level in serum of rats fed to diet deficient in threonine, (group 4), lysine (groups 3 and 4), methionine and cystine (group 4), phenylalanine and tyrosine (group 4), tryptophan (group 4) and valine (group 4) was significantly lower than that of the basal diet (group 1). Whereas, there were no significant differences in triglyceride level in serum between the basal diet and the diet deficient in leucine, isoleucine, histidine or arginine. Thus, it is assumed that the decreased level of serum triglyeride might not be necessarily related to the lipid accumulation in the liver.
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Since the first AHA Science Advisory “Fish Consumption, Fish Oil, Lipids, and Coronary Heart Disease,”1 important new findings, including evidence from randomized controlled trials (RCTs), have been reported about the beneficial effects of omega-3 (or n-3) fatty acids on cardiovascular disease (CVD) in patients with preexisting CVD as well as in healthy individuals.2 New information about how omega-3 fatty acids affect cardiac function (including antiarrhythmic effects), hemodynamics (cardiac mechanics), and arterial endothelial function have helped clarify potential mechanisms of action. The present Statement will address distinctions between plant-derived (α-linolenic acid, C18:3n-3) and marine-derived (eicosapentaenoic acid, C20:5n-3 [EPA] and docosahexaenoic acid, C22:6n-3 [DHA]) omega-3 fatty acids. (Unless otherwise noted, the term omega-3 fatty acids will refer to the latter.) Evidence from epidemiological studies and RCTs will be reviewed, and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid (plant- and marine-derived) supplementation. This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration (FDA) about the presence of environmental contaminants in certain species of fish. ### Coronary Heart Disease As reviewed by Stone,1 three prospective epidemiological studies within populations reported that men who ate at least some fish weekly had a lower coronary heart disease (CHD) mortality rate than that of men who ate none.3–6⇓⇓⇓ More recent evidence that fish consumption favorably affects CHD mortality, especially nonsudden death from myocardial infarction (MI), has been reported in a 30-year follow-up of the Chicago Western Electric Study.7 Men who consumed 35 g or more of fish daily compared with those who consumed none had a relative risk of death from CHD of 0.62 and a relative risk of nonsudden death from MI of 0.33. In an …
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Fatty acids in products claimed to contain oils with the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were analyzed as fatty acid methyl esters by gas chromatography-mass spectrometry using electron impact ionization. To cover the variation in products on the market, the 20 products that were studied in detail were selected from a larger sample set by statistical methodology. The samples were analyzed on two different stationary phases (polyethylene glycol and cyanopropyl) and the fatty acid methyl esters were identified by methodology that combines the mass spectra and retention indices into a single score value. More that 100 fatty acids had a chromatographic area above 0.1% of the total, in at least one product. Retention indices are reported as equivalent chain lengths, and overlap patterns on the two columns are discussed. Both columns were found suitable for analysis of major and nutritionally important fatty acids, but the large number of minor compounds that may act as interferents will be problematic if low limits of quantification are required in analyses of similar sample types. A database of mass spectral libraries and equivalent chain lengths of the detected compounds has been compiled and is available online.
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Animal biosynthesis of high polyunsaturated fatty acids from linoleic, α-linolenic and oleic acids is mainly modulated by the Δ6 and Δ5 desaturases through dietary and hormonal stimulated mechanisms. From hormones, only insulin activates both enzymes. In experimental diabetes mellitus type-1, the depressed Δ6 desaturase is restored by insulin stimulation of the gene expression of its mRNA. However, cAMP or cycloheximide injection prevents this effect. The depression of Δ6 and Δ5 desaturases in diabetes is rapidly correlated by lower contents of arachidonic acid and higher contents of linoleic in almost all the tissues except brain. However, docosahexaenoic n-3 acid enhancement, mainly in liver phospholipids, is not explained yet. In experimental non-insulin dependent diabetes, the effect upon the Δ6 and Δ5 desaturases is not clear. From all other hormones glucagon, adrenaline, glucocorticoids, mineralocorticoids, oestriol, oestradiol, testosterone and ACTH depress both desaturases, and a few hormones: progesterone, cortexolone and pregnanediol are inactive.
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An epidemiological survey of several chronic diseases in the Upernavik district, Northwest Greeland, is reported. The study population (ap-prox. 1 800 inhabitants) is one of the remaining whaling and sealing populations in Greenland. It was observed over the 25-year period 1950–74 as to the incidence of the diseases, which was based on all cases diagnosed in hospital during this period. The disease pattern of the Greenlanders differs from that of West-European populations, having a higher frequency of apoplexy and epilepsy but a lower frequency or absence of acute myocardial infarction, diabetes mellitus, thyrotoxicosis, bronchial asthma, multiple sclerosis and psoriasis. The distribution of cancer types differs from that of the Danish population, but the total incidence of cancer is of the same magnitude. Further comparable studies should be performed in Greenlandic districts that are characterized by more profound changes in life style, in order to elucidate the effect of these changes on the disease pattern. Acta Med Scand 208: 401, 1980.
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Sprague-Dawley rats were fed purified diets varying in both protein (20%) and lipid (11%) content for 28 d to verify the independent and interactive effects of dietary proteins and lipids on serum and hepatic lipids, and on tissue lipoprotein lipase (LPL) activity in both fasted and postprandial states. These diets consisted of either casein-menhaden oil, casein-coconut oil, soy protein-menhaden oil (SPMO), soy protein-coconut oil, cod protein-menhaden oil, or cod protein-coconut oil. A randomized 3×2 factorial design was used. A significant protein-lipid interaction was seen on serum triglyceride levels: menhaden oil, compared with coconut oil, induced a decrease in serum triglyceride levels when combined with soy protein but not when combined with cod protein and casein. The lower serum triglyceride concentrations observed in the SPMO-fed rats could be the result of decreased hepatic triglycerides when soy protein was compared with casein and when menhaden oil was compared with coconut oil. Total LPL activity in the heart was higher in menhaden oil-fed rats than in coconut oil-fed rats in the postprandial state. The higher LPL activity in the heart could, however, explain only 10% of the reduction of serum triglycerides, contributing slightly to the lowering effects of SPMO diet on serum triglycerides. Therefore, the present results indicate that dietary proteins can modulate the effects of fish oil on triglyceridemia in the rat, and that could be mainly related to specific alterations in hepatic lipid concentrations.
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The levels of trans isomers of eicosapentaenoic (EPA) acid and docosahexaenoic acid (DHA) in 77 omega-3 products on the European market have been studied. Fatty acids were analyzed as fatty acid methyl esters by gas chromatography with a flame ionization detector, using a cyanopropyl coated stationary phase. The amount of mono-trans EPA isomers relative to the corresponding all-cis isomer ranged from 0.19 to 4.5 %. The corresponding values for mono-trans DHA relative to the all-cis isomer ranged from 0.25 to 5.9 %. There was a strong correlation between the degree of isomerization of EPA and DHA, showing that DHA was 1.26 times more isomerized than EPA. Division of the samples into different product groups showed that samples with a low degree of isomerization were found in all groups, except one. This shows that a high degree of isomerization is avoidable, and also points to deodorization of the oils as the main source of trans isomers.
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Fish consumption is associated with a reduced colorectal cancer risk. A possible mechanism by which fish consumption could decrease colorectal cancer risk is by reducing inflammation. However, thus far, intervention studies investigating both systemic and local gut inflammation markers are lacking. Our objective in this study was to investigate the effects of fatty and lean fish consumption on inflammation markers in serum, feces, and gut. In an intervention study, participants were randomly allocated to receive dietary advice (DA) plus either 300 g of fatty fish (salmon) or 300 g of lean fish (cod) per week for 6 mo, or only DA. Serum C-reactive protein (CRP) concentrations were measured pre- and postintervention (n = 161). In a subgroup (n = 52), we explored the effects of the fish intervention on fecal calprotectin and a wide range of cytokines and chemokines in fecal water and in colonic biopsies. Serum CRP concentrations were lower in the salmon (-0.5 mg/L; 95% CI -0.9, -0.2) and cod (-0.4 mg/L; 95% CI -0.7, 0.0) groups compared with the DA group. None of the inflammation markers in fecal water and colonic biopsies differed between the DA group and the groups that consumed extra fish. In conclusion, increasing salmon or cod consumption for 6 mo resulted in lower concentrations of the systemic inflammation marker CRP. However, exploratory analysis of local markers of inflammation in the colon or feces did not reveal an effect of fish consumption.
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Fish protein has been shown to decrease serum cholesterol content by inhibiting absorption of cholesterol and bile acid in laboratory animals, though the mechanism underlying this effect is not yet fully understood. The purpose of this study was to elucidate the mechanism underlying the inhibition of cholesterol and bile acid absorption following fish protein intake. Male Wistar rats were divided into 2 dietary groups of 7 rats each, 1 group receiving a diet consisting of 20% casein and the other receiving a diet consisting of 10% casein and 10% fish protein. Both experimental diets also contained 0.5% cholesterol and 0.1% sodium cholate. After the rats had been on their respective diets for 4 wk, their serum and liver cholesterol contents and fecal cholesterol, bile acid, and nitrogen excretion contents were measured. Fish protein consumption decreased serum and liver cholesterol content and increased fecal cholesterol and bile acid excretion and simultaneously increased fecal nitrogen excretion. In addition, fish protein hydrolyzate prepared by in vitro digestion had lower micellar solubility of cholesterol and higher binding capacity for bile acids compared with casein hydrolyzate. These results suggest that the hypocholesterolemic effect of fish protein is mediated by increased fecal cholesterol and bile acid excretion, which is due to the digestion products of fish protein having reduced micellar solubility of cholesterol and increased bile acid binding capacity.
Article
This study was performed to assess the effects of potato protein and fish protein on concentrations of lipids in plasma and lipoproteins and the expression of genes involved in lipid metabolism in pigs used as an animal model. Therefore, 27 young male pigs with an average body weight of 22 kg were fed diets supplemented with protein extracted from potatoes (containing 849 g protein/kg dry matter), Alaska Pollack fillet as a source of fish protein (containing 926 g crude protein/kg dry matter) or casein which was used as control, for 3 weeks. Diets were formulated to supply identical amounts of each protein to the pigs by the three protein sources, namely 116 g/day in first week and 150 g/day in the second and third week. Pigs fed potato protein had lower concentrations of cholesterol in plasma and LDL than pigs fed casein (p < 0.05); no effect was observed on concentrations of HDL cholesterol and triglycerides. Pigs fed fish protein had lower cholesterol concentrations in plasma, LDL and HDL, and lower triglyceride concentrations in triglyceride-rich lipoproteins than pigs fed casein (p < 0.05). mRNA concentrations of genes involved in bile acid synthesis and cholesterol uptake were higher in pigs fed fish protein than in pigs fed casein (p < 0.05); no effect on these genes was observed in pigs fed potato protein. Expression of genes involved in lipogenesis and fatty acid oxidation was not altered by fish protein. In conclusion, this study shows that fish protein and potato protein lower plasma cholesterol concentrations in pigs. The hypocholesterolaemic effect of fish protein might be in part caused by a stimulation of bile acid synthesis; the reason for the hypocholesterolaemic effect of potato protein requires further elucidation.
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Mounting evidence suggests that the benefits of fish consumption are not limited to the well-appreciated effects of omega-3 fatty acids. We previously demonstrated that cod protein protects against the development of diet-induced insulin resistance. The goal of this study was to determine whether other fish protein sources present similar beneficial effects. Rats were fed a high-fat, high-sucrose diet containing protein from casein or fish proteins from bonito, herring, mackerel, or salmon. After 28 days, oral glucose tolerance tests or hyperinsulinemic-euglycemic clamps were performed; and tissues and plasma were harvested for biochemical analyses. Despite equal energy intake among all groups, the salmon-protein-fed group presented significantly lower weight gain that was associated with reduced fat accrual in epididymal white adipose tissue. Although this reduction in visceral adiposity was not associated with improved glucose tolerance, we found that whole-body insulin sensitivity for glucose metabolism was improved using the very sensitive hyperinsulinemic-euglycemic clamp technique. Importantly, expression of both tumor necrosis factor-α and interleukin-6 was reduced in visceral adipose tissue of all fish-protein-fed groups when compared with the casein-fed control group, suggesting that fish proteins carry anti-inflammatory properties that may protect against obesity-linked metabolic complications. Interestingly, consumption of the salmon protein diet was also found to raise circulating salmon calcitonin levels, which may underlie the reduction of weight gain in these rats. These data suggest that not all fish protein sources exert the same beneficial properties on the metabolic syndrome, although anti-inflammatory actions appear to be common.
Article
The global incidence and prevalence of obesity continue to increase, with the fastest rate of increase in the developing world. Obesity is associated with many chronic diseases including type 2 diabetes, cardiovascular disease and some cancers. Weight loss can reduce the risk of developing these diseases and can be achieved by means of surgery, pharmacotherapy and lifestyle interventions. Lifestyle interventions for prevention and treatment of obesity include diet, exercise and psychological interventions. All lifestyle interventions have a modest but significant effect on weight loss, but there is little evidence to indicate that any one intervention is more effective. There is evidence of an additive effect for adjunct therapy, and the combination of diet, exercise and behavioural interventions appears to be most effective for both the prevention and treatment of obesity.
Article
Dietary proteins influence the lipid metabolism of human subjects and animals. This study evaluated the effects of fish protein on lipid metabolism in rats. Alaska pollock fillets, widely supplied as raw materials of surimi, were used as fish protein. As parameters of lipid metabolism, cholesterol and triacylglycerol concentrations in the serum and liver, the fecal excretion of bile acids, and the hepatic expression of genes encoding proteins involved in lipid homeostasis were examined. Rats fed fish protein showed decreased cholesterol concentrations in the serum and liver, and fecal bile acid and cholesterol concentrations were increased. This was caused by the increased expression of cholesterol 7alpha-hydroxylase (CYP7A1) as the digested fish protein inhibited the absorption of bile acid and cholesterol in the small intestine. In addition, it was found that dietary fish protein affects the farnesoid X receptor/small heterodimer partner-dependent pathway, which is negatively regulated by the decreased reabsorption of bile acid. Furthermore, it increased the binding to the promoter of CYP7A1 through activated liver receptor homologue-1.
Article
Being the metabolic syndrome a multifactorial condition, it is difficult to find adequate experimental models to study this pathology. The obese Zucker rats, which are homozygous for the fa allele, present abnormalities similar to those seen in human metabolic syndrome and are a widely extended model of insulin resistance. The usefulness of these rats as a model of non-insulin-dependent diabetes mellitus is nevertheless questionable, and they neither can be considered a clear experimental model of hypertension. Some experimental models different from the obese Zucker rats have also been used to study the metabolic syndrome. Some derive from the spontaneously hypertensive rats (SHR). In this context, the most important are the obese SHR, usually named Koletsky rats. Hyperinsulinism, associated with either normal or slightly elevated levels of blood glucose, is present in these animals, but SHR/N-corpulent rats are a more appropriated model of non-insulin-dependent diabetes mellitus. The SHR/NDmc corpulent rats, a subline of SHR/N-corpulent rats, also exhibit metabolic and histopathologic characteristics associated with human metabolic disorders. A new animal model of the metabolic syndrome, stroke-prone-SHR (SHRSP) fatty rats, was obtained by introducing a segment of the mutant leptin receptor gene from the Zucker line heterozygous for the fa gene mutation into the genetic background of the SHRSP. Very recently, it has been developed as a non-obese rat model with hypertension, fatty liver and characteristics of the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein in the SHR rats. The Wistar Ottawa Karlsburg W rats are also a new strain that develops a nearly complete metabolic syndrome. Moreover, a new experimental model of low-capacity runner rats has also been developed with elevated blood pressure levels together with the other hallmarks of the metabolic syndrome.
Article
Conjugation of bile acids (BAs) to the amino acids taurine or glycine increases their solubility and promotes liver BA secretion. Supplementing diets with taurine or glycine modulates BA metabolism and enhances fecal BA excretion in rats. However, it is still unclear whether dietary proteins varying in taurine and glycine contents alter BA metabolism, and thereby modulate the recently discovered systemic effects of BAs. Here we show that rats fed a diet containing saithe fish protein hydrolysate (saithe FPH), rich in taurine and glycine, for 26 days had markedly elevated fasting plasma BA levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal/retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism.
Article
The role of dietary protein in weight loss and weight maintenance encompasses influences on crucial targets for body weight regulation, namely satiety, thermogenesis, energy efficiency, and body composition. Protein-induced satiety may be mainly due to oxidation of amino acids fed in excess, especially in diets with "incomplete" proteins. Protein-induced energy expenditure may be due to protein and urea synthesis and to gluconeogenesis; "complete" proteins having all essential amino acids show larger increases in energy expenditure than do lower-quality proteins. With respect to adverse effects, no protein-induced effects are observed on net bone balance or on calcium balance in young adults and elderly persons. Dietary protein even increases bone mineral mass and reduces incidence of osteoporotic fracture. During weight loss, nitrogen intake positively affects calcium balance and consequent preservation of bone mineral content. Sulphur-containing amino acids cause a blood pressure-raising effect by loss of nephron mass. Subjects with obesity, metabolic syndrome, and type 2 diabetes are particularly susceptible groups. This review provides an overview of how sustaining absolute protein intake affects metabolic targets for weight loss and weight maintenance during negative energy balance, i.e., sustaining satiety and energy expenditure and sparing fat-free mass, resulting in energy inefficiency. However, the long-term relationship between net protein synthesis and sparing fat-free mass remains to be elucidated.
Article
This study investigated the potential additive or synergistic effect of fish oil (FO) and fish protein hydrolysate (FPH) on cholesterol concentration in plasma and the liver. Male Wistar rats were fed high-fat diets (30% fat, 20% protein, wt/wt) containing FO (5%), FPH (10%), a combination of FO and FPH, or a high-fat control diet. After 7 wk of feeding, the rats were fasted for 12 h before lipid levels in plasma and the liver and hepatic activities of acyl-coenzyme A:cholesterol acyltransferase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and fatty acid synthase were measured. The combination of FO and FPH in the diet profoundly reduced the plasma cholesterol level, mainly due to lowering of high-density lipoprotein cholesterol, whereas the hepatic total cholesterol concentration was elevated compared with control rats and rats fed diets containing FPH or FO alone. The elevated cholesterol concentration in the liver was caused by an increased amount of cholesteryl esters and was in correlation to an increased activity of acyl-coenzyme A:cholesterol acyltransferase. There was a reduced fatty acid synthase activity that could lead to a reduced lipogenesis in the rats fed a combination of FO and FPH. A dietary combination of FO and FPH resulted in lower levels of plasma cholesterol and higher levels of hepatic cholesterol compared with dietary FO or FPH alone. Further studies are warranted to confirm whether the hypocholesterolemic effect was due to a reduced secretion of very low-density lipoprotein from the liver.
Article
Cholestyramine was administered to hamsters at 6 doses in the diet for 1 week. Plasma cholesterol, LDL + VLDL cholesterol and HDL cholesterol were measured after this period. Bile acid excretion was measured in faeces collected over the final 24 h of the experiment. A dose-response curve for each parameter measured was constructed using data from individual hamsters. For the bile acid and the cholesterol measurements a maximum response was observed at the highest doses. A correlation between the bile acids excreted over 24 h and the LDL + VLDL cholesterol showed that the maximum effect of cholestyramine on lowering plasma and lipoprotein cholesterol occurred at a submaximal excretion level of bile acids. Comparison of the efficiency of cholestyramine in reducing plasma cholesterol in the hamster with limited data in the dog and in man suggest that a greater lowering of plasma cholesterol is achieved in the dog and in man for an equivalent increase in bile acid excretion caused by the sequestrant. As is already known, cholestyramine treatment caused an increase in hepatic cholesterol 7 alpha-hydroxylase and HMG-CoA reductase activity. Interestingly in this study the novel observation was made that the bile acid sequestrant reduced the activity of hepatic acyl-CoA: cholesterol acyltransferase.
Article
To examine the association of fish intake with the subsequent risk of impaired glucose tolerance and diabetes mellitus (glucose intolerance). In 1971, information about food intake was obtained by the cross-check dietary history method on 175 men and women aged 64-87 yr who were normoglycemic and free of clinical diabetes. During the follow-up period from 1972 to 1975, an oral glucose tolerance test was performed annually, and in 59 of 175 elderly people a diagnosis of glucose intolerance was made at least once. In 1971, approximately 60% of the subjects usually ate fish, with a mean daily intake of 24.2 g. In fish eaters, the incidence of glucose intolerance was significantly lower compared with nonfish eaters (odds ratio [OR] 0.40, 95% confidence interval [CI] 0.21-0.77). With logistic regression analysis, this inverse association could not be explained by taking into account age and sex or possible confounding baseline characteristics, such as the prevalence of myocardial infarction, body mass index, energy intake per kilogram body weight, or intake of carbohydrates (OR 0.47, 95% CI 0.23-0.93). Baseline characteristics of the oral glucose tolerance test and serum triglyceride levels could also not account for this result. These results suggest that, in an elderly population, the habitual consumption of a small amount of fish may protect against the development of impaired glucose tolerance and diabetes mellitus.
Eight laboratories participated in a collaborative study to estimate precision of a standardized rat assay for determining true protein digestibility in selected animal, fish, and cereal products. Each of 7 test protein sources (casein, tuna fish, macaroni/cheese, pea protein concentrate, rolled oats, pinto beans, and nonfat dried milk) was fed as the sole source of protein at a 10% protein level in mixed diets. Each diet was fed to 2 replicate groups of 4 rats each for a 4-day acclimation period and a 5-day balance period. Mean digestibilities ranged from 98.6% for casein to 72.6% for pinto beans. Repeatability standard deviations ranged from 0.5 to 2.0%; the mean relative standard deviation for repeatability was 0.9% (range 0.5-2.8%). Reproducibility standard deviations ranged from 1.2 to 3.2%, and the mean relative standard deviation for reproducibility was 2.4% (range 1.3-4.4%). The method has been approved interim official first action for determining true protein digestibility in foods and ingredients.
Article
The effects of dietary fish, soybean protein and casein on cholesterol turnover were compared in rats. After the injection of [14C]cholesterol into the rats, the specific activities of radioactive cholesterol in feces were followed for 4 weeks. The cholesterol half-lives calculated from the decay curves of the specific activities were 14.7 and 14.6 days in rats fed fish protein and soybean protein, respectively. These were shorter than the half-life (17.4 days) in casein-fed controls. The fish and the soybean protein feedings significantly increased the fecal excretions of cholesterol and coprostanol, respectively, and lowered the plasma cholesterol level, as compared with casein feeding. In addition, both fish and soybean protein feedings also increased the excretion of bile acids. The stimulation of cholesterol metabolism and the increased excretions of cholesterol and its metabolites by feeding fish or soybean protein appear to play important roles in the hypocholesterolemic effects.
Article
An epidemiological survey of several chronic diseases in the Upernavik district, Northwest Greenland, is reported. The study population (approx. 1800 inhabitants) is one of the remaining whaling and sealing populations in Greenland. It was observed over the 25-year period 1950-74 as to the incidence of the diseases, which was based on all cases diagnosed in hospital during this period. The disease pattern of the Greenlanders differs from that of West-European populations, having a higher frequency of apoplexy and epilepsy but a lower frequency or absence of acute myocardial infarction, diabetes mellitus, thyrotoxicosis, bronchial asthma, multiple sclerosis and psoriasis. The distribution of cancer types differs from that of the Danish population, but the total incidence of cancer is of the same magnitude. Further comparable studies should be performed in Greenlandic districts that are characterized by more profound changes in life style, in order to elucidate the effect of these changes on the disease pattern.
Article
Tumor necrosis factor-alpha (TNF-alpha) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-alpha messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-alpha protein was also elevated locally and systemically. Neutralization of TNF-alpha in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.
Article
Sesamin, present in sesame seed oil (SSO), can inhibit delta-5-desaturase activity and cause accumulation of dihomo-gamma-linolenic acid (DGLA), which displaces arachidonic acid, and subsequently decrease production of dienoic eicosanoids. The effects of diets containing both SSO and Quil A, a saponin that emulsifies fats and potentiates the immune responses, were also studied. A mixture of oils having a fatty-acid composition similar to that of SSO served as a control diet. The levels of docosapentaenoic acid in mice fed Quil-A-supplemented diets and of DGLA in those fed SSO diets were markedly higher in the liver. These changes were associated with a significant reduction in the plasma prostaglandin-E(1+2) and thromboxane-B2 levels in response to an intraperitoneal injection of a lethal dose of lipopolysaccharide (LPS) endotoxin (LD50 20 mg/kg). The levels of interleukin (IL-)6 were elevated and those of IL-1beta were decreased in mice consuming Quil-A-supplemented diets. The IL-10 levels that were elevated in all mice after LPS exposure, remained higher (even at 9 h) only in those fed Quil-A-supplemented diets, but declined rapidly in others. During a 48-hour observation period following LPS injection, all control animals died, and survival was 40% in the SSO group, and 27 and 50%, respectively, in those fed Quil-A-supplemented control and SSO diets. These data suggest that SSO and Quil A when present in the diet exerted cumulative effects that resulted in a decrease in the levels of dienoic eicosanoids with a reduction in IL-1beta and a concomitant elevation in the levels of IL-10 that were associated with a marked increase in survival in mice.
Article
The aim of the present study was to determine the effects of feeding various dietary proteins on insulin sensitivity and glucose tolerance in rats. Male Wistar rats were fed for 28 days with isoenergetic diets containing either casein, soy protein, or cod protein. Cod protein-fed and soy protein-fed rats had lower fasting plasma glucose and insulin concentrations compared with casein-fed animals. After intravenous glucose bolus, cod protein- and soy protein-fed rats induced lower incremental areas under glucose curves compared with casein-fed animals. Improved peripheral insulin sensitivity was confirmed by higher glucose disposal rates in cod protein- and soy protein-fed rats (15.2 +/- 0.3 and 13.9 +/- 0.6 mg. kg(-1). min(-1), respectively) compared with casein-fed animals (6.5 +/- 0.7 mg. kg(-1). min(-1), P < 0.05). Moreover, test meal experiments revealed that, in the postprandial state, the lower plasma insulin concentrations in cod protein- and soy protein-fed animals could be also due to decreased pancreatic insulin release and increased hepatic insulin removal. In conclusion, the metabolic responses to three common dietary proteins indicate that cod and soy proteins, when compared with casein, improve fasting glucose tolerance and peripheral insulin sensitivity in rats.
Article
In the present study, we tested the hypothesis that fish protein may represent a key constituent of fish with glucoregulatory activity. Three groups of rats were fed a high-fat diet in which the protein source was casein, fish (cod) protein, or soy protein; these groups were compared with a group of chow-fed controls. High-fat feeding led to severe whole body and skeletal muscle insulin resistance in casein- or soy protein-fed rats, as assessed by the euglycemic clamp technique coupled with measurements of 2-deoxy-D-[(3)H]glucose uptake rates by individual tissues. However, feeding cod protein fully prevented the development of insulin resistance in high fat-fed rats. These animals exhibited higher rates of insulin-mediated muscle glucose disposal that were comparable to those of chow-fed rats. The beneficial effects of cod protein occurred without any reductions in body weight gain, adipose tissue accretion, or expression of tumor necrosis factor-alpha in fat and muscle. Moreover, L6 myocytes exposed to cod protein-derived amino acids showed greater rates of insulin-stimulated glucose uptake compared with cells incubated with casein- or soy protein-derived amino acids. These data demonstrate that feeding cod protein prevents obesity-induced muscle insulin resistance in high fat-fed obese rats at least in part through a direct action of amino acids on insulin-stimulated glucose uptake in skeletal muscle cells.
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Animal biosynthesis of high polyunsaturated fatty acids from linoleic, alpha-linolenic and oleic acids is mainly modulated by the delta6 and delta5 desaturases through dietary and hormonal stimulated mechanisms. From hormones, only insulin activates both enzymes. In experimental diabetes mellitus type-1, the depressed delta6 desaturase is restored by insulin stimulation of the gene expression of its mRNA. However, cAMP or cycloheximide injection prevents this effect. The depression of delta6 and delta5 desaturases in diabetes is rapidly correlated by lower contents of arachidonic acid and higher contents of linoleic in almost all the tissues except brain. However, docosahexaenoic n-3 acid enhancement, mainly in liver phospholipids, is not explained yet. In experimental non-insulin dependent diabetes, the effect upon the delta6 and delta5 desaturases is not clear. From all other hormones glucagon, adrenaline, glucocorticoids, mineralocorticoids, oestriol, oestradiol, testosterone and ACTH depress both desaturases, and a few hormones: progesterone, cortexolone and pregnanediol are inactive.
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Omega-3 fatty acids have been shown in epidemiological and clinical trials to reduce the incidence of CVD. Large-scale epidemiological studies suggest that individuals at risk for CHD benefit from the consumption of plant- and marine-derived omega-3 fatty acids, although the ideal intakes presently are unclear. Evidence from prospective secondary prevention studies suggests that EPA+DHA supplementation ranging from 0.5 to 1.8 g/d (either as fatty fish or supplements) significantly reduces subsequent cardiac and all-cause mortality. For α-linolenic acid, total intakes of ≈1.5 to 3 g/d seem to be beneficial. Collectively, these data are supportive of the recommendation made by the AHA Dietary Guidelines to include at least two servings of fish per week (particularly fatty fish). In addition, the data support inclusion of vegetable oils (eg, soybean, canola, walnut, flaxseed) and food sources (eg, walnuts, flaxseeds) high in α-linolenic acid in a healthy diet for the general population (Table 5). The fish recommendation must be balanced with concerns about environmental pollutants, in particular PCB and methylmercury, described in state and federal advisories. Consumption of a variety of fish is recommended to minimize any potentially adverse effects due to environmental pollutants and, at the same time, achieve desired CVD health outcomes. RCTs have demonstrated that omega-3 fatty acid supplements can reduce cardiac events (eg, death, nonfatal MI, nonfatal stroke) and decrease progression of atherosclerosis in coronary patients. However, additional studies are needed to confirm and further define the health benefits of omega-3 fatty acid supplements for both primary and secondary prevention. For example, placebo-controlled, double-blind RCTs are needed to document both the safety and efficacy of omega-3 fatty acid supplements in both high-risk patients (eg, patients with type 2 diabetes, dyslipidemia, and hypertension, and smokers) and coronary patients on drug therapy. Mechanistic studies on their apparent effects on sudden death are also needed. A dietary (ie, food-based) approach to increasing omega-3 fatty acid intake is preferable. Still, for patients with coronary artery disease, the dose of omega-3 (≈1 g/d) may be greater than what can readily be achieved through diet alone (Table 5). These individuals, in consultation with their physician, could consider supplements for CHD risk reduction. Supplements also could be a component of the medical management of hypertriglyceridemia, a setting in which even larger doses (2 to 4 g/d) are required (Table 5). The availability of high-quality omega-3 fatty acid supplements, free of contaminants, is an important prerequisite to their extensive use.
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To investigate the effect of two types of dietary protein on blood pressure, liver fatty acid desaturation and composition, and urine 6-keto-prostaglandin-F (PGF(1alpha)) level, the metabolite of prostacyclin. 5-wk-old spontaneously hypertensive rats were fed 20% casein or purified fish protein. The fat source was 5% ISIO oil, which contains 47.9% (omega-6) and 1.7% (omega-3) total polyunsaturated fatty acids. After 2 mo on the diet, systolic blood pressure was reduced with fish protein compared with casein (189.8 +/- 10.5 versus 220.7 +/- 8.7). Excretion of 6-keto-PGF(1alpha) in urine was negatively correlated with blood pressure. Liver cholesterol and phospholipid concentrations were 1.71- and 1.27-fold lower with fish protein than with casein, respectively. The fish protein diet lowered the 20:4(omega-6) proportion and the ratio of 20:4(omega-6) to 18:2(omega-6) in liver microsomal lipids and phospholipids, which was due to the reduced microsomal Delta6(omega-6) desaturation activity. Dietary protein source did not affect omega-3 fatty acid composition, and this was associated with a similar activation of Delta6(omega-3) desaturation in liver microsomes. The present data indicated a significant blood pressure-lowering effect caused by fish protein, rather than by casein, that modified the fatty acid composition of liver phospholipids and liver microsomal total lipids.
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Lipid decomposition studies in frozen fish have led to the development of a simple and rapid method for the extraction and purification of lipids from biological materials. The entire procedure can be carried out in approximately 10 minutes; it is efficient, reproducible, and free from deleterious manipulations. The wet tissue is homogenized with a mixture of chloroform and methanol in such proportions that a miscible system is formed with the water in the tissue. Dilution with chloroform and water separates the homogenate into two layers, the chloroform layer containing all the lipids and the methanolic layer containing all the non-lipids. A purified lipid extract is obtained merely by isolating the chloroform layer. The method has been applied to fish muscle and may easily be adapted to use with other tissues.Lipid decomposition studies in frozen fish have led to the development of a simple and rapid method for the extraction and purification of lipids from biological materials. The entire procedure can be carried out in approximately 10 minutes; it is efficient, reproducible, and free from deleterious manipulations. The wet tissue is homogenized with a mixture of chloroform and methanol in such proportions that a miscible system is formed with the water in the tissue. Dilution with chloroform and water separates the homogenate into two layers, the chloroform layer containing all the lipids and the methanolic layer containing all the non-lipids. A purified lipid extract is obtained merely by isolating the chloroform layer. The method has been applied to fish muscle and may easily be adapted to use with other tissues.