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Dietary Fat Influences Testosterone, Cholesterol, Aminopeptidase A, and Blood Pressure in Male Rats

Short Communication 1
Segarra AB et al. Dietary Fat and Blood Pressure Control Horm Metab Res 2008 ; 40: 1 – 3
DOI 10.1055/s-2008-1046800
Horm Metab Res 2008 ;
40: 1 – 3
© Georg Thieme Verlag KG
Stuttgart · New York
ISSN 0018-5043
M. Ramirez
Unit of Physiology
University of Ja é n
Bldg B-3-263
23071 Ja é n
Fax: + 34 / 953 / 21 29 43
Dietary Fat Infl uences Testosterone, Cholesterol,
Aminopeptidase A, and Blood Pressure in Male Rats
Authors A . B . S e g a r r a
, M . R a m i r e z
, I . B a n e g a s
, F. A l b a
, F. V i v e s
, M . d e G a s p a r o
, E . O r t e g a
, E . R u i z
, I. Prieto
Affi liations
Unit of Physiology, University of Ja é n, Ja é n, Spain
Department of Biochemistry and Molecular Biology, University of Granada, Granada, Spain
Department of Physiology, University of Granada, Granada, Spain
MG Consulting Co., Rossemaison, Switzerland
A high intake of monounsaturated fat (MUFA)
has been proposed to be a dietary factor able to
decrease the incidence of cardiovascular disease
and hypertension [1] . It has been shown that an
increase in the saturation of dietary fat results in
increased concentrations of total plasma choles-
terol [2] and higher blood pressure [3] . It was
previously shown that serum total cholesterol
levels were higher in mice fed diets containing
saturated oils than in those consuming unsatu-
rated fat. In addition, angiotensin II – degrading
(aminopeptidase A) activity increased progres-
sively with the degree of saturation of dietary
fatty acids [4] . A subsequent study found that
dietary fatty acid composition affected amino-
peptidase A activity in the testes of mice, sug-
gesting a role for fatty acids in male reproductive
functions, including androgen synthesis [5] . It
was recently observed that a diet enriched with
Iberian pig lard remarkably increased serum tes-
tosterone levels in comparison to diets contain-
ing other types of fatty acids with different
degrees of saturation [6] . This and other studies
suggested an infl uence of gonadal steroids and
cholesterol on angiotensin-degrading activities
[7] . Other actions of gonadal steroids by non-
genomic-dependent mechanisms have been
reported, such as stimulation of insulin secretion
and Ca
2 +
uptake as well as vasodilatory effects
[8, 9] . In the present report we analyze the effect
of various diets enriched in fatty acids with dif-
ferent degrees of saturation on systolic blood
pressure, plasma levels of testosterone, total cho-
lesterol, HDL cholesterol, LDL cholesterol, and
angiotensin II – degrading activity.
Materials and Methods
Six groups of adult male Wistar rats (200 250 g,
n = 8 in each group) were fed with isocaloric diets
for 16 weeks. Each diet was supplemented with
10 % of the oil under investigation: sesame oil,
sunfl ower oil, fi sh oil, olive oil, Iberian pig lard, or
coconut oil. The characteristics of the different
types of dietary fat compared in this study are
summarized in Table 1 [10, 11] .
At the end of the feeding period, systolic blood
pressure in each rat was recorded, and then the
animals were killed by Equithesin anesthesia.
Blood samples were obtained and plasma was
isolated by centrifugation for 10 minutes at
2000 g and stored at 20 ° C. Plasma testosterone
levels were measured by radioimmunoassay as
previously reported [6] and expressed as nano-
grams per milliliter. Cholesterol levels were
determined colorimetrically with a commercial
kit purchased from Sigma. Aminopeptidase A
activity was determined with a fl uorometric
assay using glutamyl- -naphthylamide as the
substrate, as previously described [12] . Systolic
blood pressure was measured with a tail-cuff
plethysmograph (LE 5001 Pressure Meter, Letica
SA, Barcelona, Spain) in trained, unanesthetized
animals as previously reported [13] . For the sta-
tistical analysis we used one-way analysis of
variance to analyze differences between groups.
Post-hoc comparisons were made with Tukey s
test. P-values below 0.05 were considered signi-
Results and Discussion
The results are summarized in
F i g . 1 . R a t s f e d
with the fi sh oil or Iberian pig lard diet had sig-
nifi cantly lower blood pressure, plasma total
cholesterol, and LDL cholesterol (p < 0.001) than
animals fed with the other diets. Plasma HDL
Short Communication2
Segarra AB et al. Dietary Fat and Blood Pressure Control Horm Metab Res 2008 ; 40: 1 – 3
cholesterol was higher in rats fed the olive oil, Iberian pig lard,
and coconut oil diets but was signifi cantly lower (p < 0.01) in ani-
mals given the sesame oil diet. The sunfl ower and fi sh oil diets
showed a tendency toward lower HDL cholesterol, but the dif-
ferences did not reach statistical signifi cance. Testosterone lev-
els were signifi cantly higher (ranging from two-fold to four-fold)
in animals fed the Iberian pig lard enriched diet than in rats fed
olive oil (p < 0.001), sh oil (p < 0.01), or sesame, sunfl ower, or
Table 1 Fatty acid composition of food fats (grams fatty acid per 100 g total fatty acids)
Fatty acid type Sesame oil [11] Sunfl ower oil [11] Fish oil [11] Olive oil [11] Iberian pig lard [10] Coconut oil [11]
caprylic 10.1
capric 6.6
lauric 45.8
myristic 0.1 4.5 1.2 18.4
palmic 8.9 6.6 0.6 11.8 20.0 8.0
palmitoleic 0.3 0.1 22.1 0.9 2.9
hexadecadienoic 2.8
margaric 0.8
stearic 6.0 4.3 6.1 2.8 6.3 2.4
oleic 40.7 22.4 21.7 74.5 59.1 6.0
linoleic 41.7 65.2 2.1 8.7 9.4 1.7
linolenic 1.7 0.3 1.2 1.0
stearidonic 0.5
arachidic 0.8 0.4
eicosenoic 2.0
arachidonic 3.0
timnodonic 13.2
behenic 0.7
docosapentaenoic 1.5
clupanodonic 17.3
SAFA 15.7 12 12 13.2 27.6 86.5
MUFA 41 22.4 45.8 73.2 62 5.8
PUFA 43.4 60.7 41.6 8.9 9.4 1.8
SAFA / MUFA 0.38 0.53 0.26 0.18 0.44 14.9
SAFA / PUFA 0.36 0.19 0.28 1.4 2.9 48.0
SAFA = saturated fatty acids; MUFA = monounsaturated fatty acids; PUFA = polyunsaturated fatty acids
pmol/min/mg prot
Fig. 1 Systolic blood pressure and plasma levels of testosterone, total cholesterol, HDL cholesterol, LDL cholesterol, and aminopeptidase A activity in adult
male Wistar rats fed diets enriched with sesame oil (S), sunfl ower oil (SF), fi sh oil (F), olive oil (O), Iberian pig lard (L), or coconut oil (C). Values are means ±
SEM, n = 8. Total cholesterol was signifi cantly lower in groups F and L than in the other groups. HDL cholesterol was signifi cantly lower in group S than in groups
L and C. LDL cholesterol was signifi cantly lower in group L than in groups S, SF, O, and C and was signifi cantly lower in group F than in group C. Testosterone
concentration was signifi cantly higher in group L than in the other groups. Aminopeptidase A was signifi cantly lower in group S than in groups SF, O, L, and C
and was signifi cantly lower in group F than in group L. Systolic blood pressure was signifi cantly lower in groups L and F than in groups S, SF, O, and C. * p < 0.05,
* * p < 0.01, * * * p < 0.001.
Short Communication 3
Segarra AB et al. Dietary Fat and Blood Pressure Control Horm Metab Res 2008 ; 40: 1 – 3
coconut oil (p < 0.05). The diet containing sesame oil signifi cantly
decreased (p < 0.001) aminopeptidase A activity compared with
the other types of dietary fat except for fi sh oil, whereas in ani-
mals fed the latter diet, aminopeptidase A activity was lower
(p < 0.001) than in the Iberian pig lard group. Interestingly, only
rats treated for 16 weeks with the Iberian pig lard diet showed a
marked increased in plasma testosterone levels, which paral-
leled a reduction in total and LDL cholesterol and a decrease in
blood pressure.
To our knowledge, the only comparable study published to date
on the infl uence of fatty acid saturation is a previous report by
Arechaga and colleagues [4] . In this study Balb / C mice were
treated with different diets containing 2.4 g fat per 100 g for 10
weeks. The diet containing pig lard signifi cantly increased total
cholesterol compared with mice fed a diet enriched with sun-
ower oil. No difference in aminopeptidase A activity was
observed between the group that consumed pig lard and the
other groups. However, it should be noted that the present study
differed in the experimental model used (rats rather than mice),
the duration of treatment (16 weeks rather than 10 weeks), and
the degree of fat enrichment of the diet (10 g per 100 g food vs.
2.4 g per 100 g). The most important difference is that Iberian pig
lard differs in composition from the pig lard used by Arechaga
and colleagues, which was rich in oleic acid C18:1 (41.1 % ), satu-
rated fatty acids (SAFA; 37.4 % ), monounsaturated fatty acids
(MUFA; 45.9 % ), and polyunsaturated fatty acids (PUFA; 11.3 % )
[4] . In contrast, Iberian pig lard contains a higher percentage of
MUFA + PUFA (62 + 9.5 % ) (mainly oleic C18:1, 59.1 % ) compared
with SAFA (27.6 % ). We therefore propose that the discrepancy
between the two studies is related to the difference in the
unsaturated / saturated fat ratios of the different lard-containing
diets. Indeed, the SAFA / MUFA ratio is 0.44 for Iberian pig lard
and 0.81 for regular pig lard, and the SAFA / PUFA ratio is 2.9 for
Iberian pig lard and 3.4 for regular pig lard. The most remarkable
nding is the greater effect of the Iberian pig lard diet on testo-
sterone and lipid levels compared with the effects of other fat-
enriched diets.
The benefi cial effects of testosterone [14] and the deleterious
infl uence of dyslipidemia [15] on cardiovascular function are
well documented. The high levels of aminopeptidase A activity
in animals that consumed the Iberian pig lard enriched diet
might refl ect the decreased pressor responsiveness to angio-
tensin II caused by increased inactivation of angiotensin II by the
enzyme. Angiotensin II is indeed metabolized to angiotensin III
by aminopeptidase A activity [12] . Moreover, angiotensin II is
considered the main effector peptide of the renin angiotensin
system, and more than a century of research has documented its
widespread involvement in the pathophysiology of cardiovascu-
lar disease [16] .
However, while both sesame oil and fi sh oil decrease amino-
peptidase A activity, only fi sh oil produces a fall in blood pres-
sure. There is therefore an apparent discrepancy with Iberian pig
lard in that it increases aminopeptidase A activity but also
decreases blood pressure. It should be noted, however, that ses-
ame oil does not improve the lipid profi le. Moreover, there is a
signifi cant decrease in HDL cholesterol for the sesame oil group.
In contrast, both fi sh oil and Iberian pig lard have a clear benefi -
cial effect on lipids. This suggests that aminopeptidase A is not
the only or main factor that infl uences blood pressure. There is
no doubt that lipids have a direct effect on vessel walls and
therefore control their stiffness [17] . The benefi cial effect of fi sh
oil on the lipid profi le may therefore compensate for the
decreased aminopeptidase A activity, which is not the case for
the sesame oil. The lipid profi le, together with the level of testo-
sterone, that results from the type of fat used in the diet may
therefore account (in part) for that discrepancy.
Taken together, the present results suggest that the use of Ibe-
rian pig lard (a type of fat with a low SAFA / MUFA ratio and a
moderately low SAFA / PUFA ratio) in the diet may benefi t cardio-
vascular function in adult male rats. The effect of dietary Iberian
pig lard also should be investigated in female rats to gain a fuller
understanding of the present results, which suggest a benefi cial
role for testosterone.
This research and work done by A. B. Segarra were supported by
a grant from the University of Ja é n, (ref. UJA2003-015). The
authors thank K. Shashok for improving the use of English in the
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... The reduction in SAFA in substitution by MUFA attenuates the increase in blood pressure (BP) [4]. These alterations, depending on the degree of fatty acid saturation, are related to changes in the systemic or local renin-angiotensin systems (RAS) [5][6][7][8][9][10]. The activation of the RAS participates in the development of MetS, heart failure [11], and pathophysiology of hypertension [4,7,[12][13][14][15][16][17][18][19][20][21][22][23][24][25]. ...
... [4,7,9]. Elevated plasma cholesterol levels are another important risk factor widely recognized for its relationship with angiotensin metabolism [4,5,7,10,12,72], with Mediterranean countries showing lower rates of heart disease than other countries due to the usual diet rich in olive oil [75]. ...
... HFDs alter the baroreceptor reflex [76], and the type of fatty acid that makes up the diet is capable of modulating the central [10,26,77] and local RAS regulatory APs [4,5,7,9,57]. Our results show that the VOO diet favored the stabilization of the RAS with respect to the Bch diet, by lowering the values of GluAP (mb) activities in the aorta, ArgAP (mb) in the ventricle and aorta, and CysAP (mb) in the atrium. ...
Full-text available
(1) Background: The replacement of diets high in saturated fat (SAFA) with monounsaturated fatty acids (MUFA) is associated with better cardiovascular function and is related to the modulation of the activity of the local renin–angiotensin system (RAS) and the collagenase activity of dipeptidyl peptidase IV (DPP-IV). The objective of the work was to verify the capacity of different types of dietary fat on the regulatory activities of RAS and DPP-IV. (2) Methods: Male Wistar rats were fed for 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or with butter (20%) plus cholesterol (0.1%) (Bch). The proteolytic activities were determined by fluorometric methods in the soluble (sol) and membrane-bound (mb) fractions of the left ventricle and atrium, aorta, and plasma samples. (3) Results: With the VOO diet, angiotensinase values were significantly lower than with the Bch diet in the aorta (GluAP and ArgAP (mb)), ventricle (ArgAP (mb)) and atrium (CysAP (sol)). Significant decreases in DPP-IV (mb) activity occurred with the Bch diet in the atrium and aorta. The VOO diet significantly reduced the activity of the cardiac damage marker LeuAP (mb) in the ventricle and aorta, except for LeuAP (sol) in the ventricle, which was reduced with the Bch diet. (4) Conclusions: The introduction into the diet of a source rich in MUFA would have a beneficial cardiovascular effect on RAS homeostasis and cardiovascular functional stability.
... On the other hand, the reduction of saturated fatty acids in substitution by other sources of mono-/poly-unsaturated fatty acids attenuated the development of hypertension. These alterations depending on the degree of saturation of the fatty acid could be related to changes in the systemic or local renin angiotensin systems (RAS) [14,15] including the kidneys, due to their direct association with the development of hypertension [16][17][18]. ...
... Different local RASs could be affected by changes in the degree of saturation of fat consumed in the diet. Within these local systems, angiotensin peptides are metabolized by various enzymes of the aminopeptidase (AP) family, also called angiotensinases, and previous results of our research group have shown that the activities of these peptidases are affected by the type of fatty acids consumed with the diet [5,14,25,26]. These APs are relevant in the control of blood pressure (BP) and renal function, participating in the regulation of the systemic and local RAS, but also like predictive renal injury biomarkers on the luminal surface of the renal tubule [27,28]. ...
... Among them, aspartyl-AP activities (AspAP; EC, responsible for the metabolism of Ang I to Ang 2-10; glutamyl-AP (GluAP or aminopeptidase A, APA; EC, metabolizes Ang II into Ang III; alanyl-AP (AlaAP or aminopeptidase M, APM; EC and/or arginyl-AP (ArgAP or aminopeptidase B, APB; EC, responsible for the metabolism of Ang III to Ang IV and Ang 4-8; insulin-regulated AP (IRAP;, also called placental AP-leucyl (LAP), cystinyl-AP (CysAP), oxytokinase or vasopressinase, which as mentioned above, was identified as the binding site for the AT4 receptor Ang IV [29][30][31][32]. It has been suggested that the metabolizing activity of Ang II (GluAP) may be influenced by the composition of fatty acids in the diet and by the cholesterol content [5,14,15,33] directly or indirectly, and with an important role in the development of cardiovascular and kidney disorders. ...
Full-text available
High saturated fat diets have been associated with the development of obesity and hypertension, along with other pathologies related to the metabolic syndrome. In contrast, the Mediterranean diet, characterized by its high content of monounsaturated fatty acids, has been proposed as a dietary factor capable of positively regulating cardiovascular function. These effects have been linked to changes in the local renal renin angiotensin system (RAS) and the activity of the sympathetic nervous system. The main goal of this study was to analyze the role of two dietary fat sources on aminopeptidases activities involved in local kidney RAS. Male Wistar rats (six months old) were fed during 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or the standard diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). Kidney samples were separated in medulla and cortex for aminopeptidase activities (AP) assay. Urine samples were collected for routine analysis by chemical tests. Aminopeptidase activities were determined by fluorometric methods in soluble (sol) and membrane-bound (mb) fractions of renal tissue, using arylamide derivatives as substrates. After the experimental period, the systolic blood pressure (SBP) values were similar in standard and VOO animals, and significantly lower than in the Bch group. At the same time, a significant increase in GluAP and IRAP activities were found in renal medulla of Bch animals. However, in VOO group the increase of GluAP activity in renal medulla was lower, while AspAP activity decreased in the renal cortex. Furthermore, the VOO diet also affected other aminopeptidase activities, such as TyrAP and pGluAP, related to the regulation of the sympathetic nervous system and the metabolic rate. These results support the beneficial effect of VOO in the regulation of SBP through changes in local AP activities of the kidney.
... (B) Relative percentages of saturated (SAFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids in the oils used in the present study to enrich the different types of diets: Respectively (SAFA, MUFA, PUFA), for sesame- (15.7, 41, 43.4), sunflower-(12, 22.4, 60.7), fish- (12, 45.8, 41.6), olive-(13.2, 73.2, 8.9), 62,9.4), and coconut-oil (86.5, 5.8, 1.8) (Segarra et al., 2008). (C) Mean ± S.E.M. levels (n = 8) of AlaAP and CysAP activities (nmol/min/mg prot) obtained in frontal cortex, liver and plasma of male rats fed during 16 weeks with diets enriched with sesame-(S, charcoal), sunflower-(SF, rose), fish-(F, gray), olive-(O, cyan), Iberian lard-(L, magenta) and coconut-oil (C, brown). ...
... The type of fat in the diet modifies the profile of fatty acids and the levels of certain neuropeptidase activities in frontal cortex (Segarra et al., , 2019a as well as the levels of cholesterol in plasma (Segarra et al., 2008). In addition, the type of fat in the diet affects the correlation between some neuropeptidase activities and certain fatty acids in frontal cortex (Segarra et al., , 2019a. ...
... Forty eight adult male Wistar rats, weighing 200-250 g (aged 3-4 months) at the beginning of the study, were divided in six groups (n = 8 each), individually housed in metabolic cages and kept under standard environmental conditions. To ensure a full effect of the diets on experimental animals and based on the average length of the diet used in the literature, each group was fed during 16 weeks with isocaloric diets supplemented with 10% of the different oils studied: S, SF, F, O, L, and C (Segarra et al., 2008). At the end of the feeding period, the rats were weighed and their systolic blood pressure recorded by plethysmography (Segarra et al., 2008). ...
Full-text available
Insulin-regulated aminopeptidase (IRAP, cystinyl aminopeptidase, CysAP) and aminopeptidase M (alanyl aminopeptidase, AlaAP) are closely related enzymes involved in cognitive, metabolic, and cardiovascular functions. These functions may be modulated by the type of fat used in the diet. In order to analyze a possible coordinated response of both enzymes we determined simultaneously their activities in frontal cortex, liver, and plasma of adult male rats fed diets enriched with fats differing in their percentages of saturated, mono or polyunsaturated fatty acids such as sesame, sunflower, fish, olive, Iberian lard, and coconut. The systolic blood pressure, food intake, body and liver weight as well as glucose and total cholesterol levels in plasma were measured. The type of fat in the diet influences the enzymatic activities depending on the enzyme and its location. These results suggest cognitive improvement properties for diets with predominance of polyunsaturated fatty acids. Physiological parameters such as systolic blood pressure, food intake, and biochemical factors such as cholesterol and glucose in plasma were also modified depending on the type of diet, supporting beneficial properties for diets rich in mono and polyunsaturated fatty acids. Inter-tissue correlations between the analyzed parameters were also modified depending on the type of diet. If the type of fat used in the diet modifies the behavior and relationship between CysAP and AlaAP in and between frontal cortex, liver and plasma, the functions in which they are involved could also be modified.
... Plasma was isolated by centrifugation of blood samples for 10 min at 2000 g using heparin as an anticoagulant and stored at −20 °C 8 . Total plasma cholesterol was determined colorimetrically using kits supplied by Sigma (St Louis, MO, 352-50) 44 . HDL cholesterol precipitated with phosphotungstic acid was quantified with the same method 44 . ...
... Total plasma cholesterol was determined colorimetrically using kits supplied by Sigma (St Louis, MO, 352-50) 44 . HDL cholesterol precipitated with phosphotungstic acid was quantified with the same method 44 . LDL cholesterol fractions were calculated using Friedewald's formula 44 . ...
... HDL cholesterol precipitated with phosphotungstic acid was quantified with the same method 44 . LDL cholesterol fractions were calculated using Friedewald's formula 44 . NO levels in plasma and urine were analyzed as previously described 36 . ...
Full-text available
A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some vasoactive drugs and linked to certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection between the brain and physiologic parameters and metabolic factors from plasma and urine. To assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological parameters and metabolic factors from plasma and urine were determined using routine laboratory techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral pattern by changing the predominance of the correlations between peripheral parameters and central neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between SHR and WKY rats. These results support an asymmetric integrative function of the organism and suggest the possibility of a different neurometabolic response coupled to particular mood disorders, depending on the selected vasoactive drug.
... Local RASs could be altered by different degrees of saturation in dietary fat. Angiotensin peptides are metabolized by several angiotensinases, and we have previously demonstrated that those activities are affected by dietary fatty acids [5,29,30]. ...
... The relative amounts of angiotensines are regulated by the activity of several aminopeptidases, namely angiotensinases ( Figure 3A). It is known that these activities are modulated by dietary fat [5,29,30,54,81,82]. Previous results have demonstrated that liver angiotensinases are altered by the thyroid status [83] and obesity [84,85]. ...
Full-text available
High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of β-cell usefulness (% β-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism.
... It is well established that the content of monoamines, particularly dopamine, is asymmetrically distributed in the brain and that a unilateral alteration of this distribution is part of the pathogenesis of Parkinson's disease in which not only motor alterations appear but also it is accompanied by depression and autonomic disturbances [33]. Certainly, the use of a polyunsaturate's enriched diet, compared to other diets, significantly modifies the content of fatty acids in the frontal cortex, especially increasing n3 PUFA [52]. Furthermore, it has been described that alterations in the n3 PUFA content in the diet are associated with alterations in the bilateral cerebral behavior possibly responsible for cognitive disorders [53]. ...
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Although at present depression is one of the most disabling disorders in our social environment, the understanding of its pathogenesis and the resources for its treatment are still unsatisfactory. The importance of brain asymmetry in the pathogenesis of disorders in brain function, including mood disorders such as depression, is a highly unexplored, sometimes underrated, and even ignored topic. It is important to note that the basal and pathological functional lateralization must have an underlying neurochemical substrate. It is also necessary to indicate that the brain asymmetry extends to a neurovisceral integration whose behavior may also be lateralized. One of the most studied axis from the functional point of view is the brain-heart connection, in whose operation there are observations that suggest an asymmetric behavior in basal conditions that is modified by central and peripheral changes, as well as by pharmacological treatments. There are evidences that connect cardiovascular function, neurochemical asymmetries, and depression. A deep understanding of the bilateral behavior of the brain following pathophysiological changes in blood pressure as well as pharmacologically induced, can provide us with therapeutic suggestions for the treatment of depression. In this article, we analyze remarkable results of some representative selected contributions, with which we discuss our proposal on the relationship between hypertension, depression and neurochemical asymmetry.
... Three groups (n=8 each) of normal adult male Wistar rats (six-week-old, weighing 200-250 g, kept at room temperature of 22 ± 2ºC, with a relative humidity of 50-60% and a photoperiod of 12/12 h light/dark cycle) were individually housed in metabolic cages. Each group was fed during 16 weeks with an isocaloric diet supplemented with 10% of the oil under investigation: fish oil (F), olive oil (O) or coconut oil (C) (Segarra et al. 2008). Body weight (g) and food intake (g/day) were monitored throughout all the experimental period. ...
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Objective. Enkephalins are neuropeptides involved in functions such as pain modulation and/ or cognitive processes. It has been reported that dietary fat modifies enkephalins in the brain. Since enkephalins are hydrolyzed by enkephalinases, the study of the influence of dietary fats, differing in their degree of saturation, on brain fatty acids content and enkephalinase activity is important to understand its regulatory role on neuropeptides under different type of diets. Methods. We analyzed enkephalinase activity, assayed with alanine-β-naphthylamide as sub-strate, in frontal cortex of adult male rats fed diets supplemented with fish oil, olive oil or coconut oil, which markedly differed in the saturation of their fatty acids. Results. Rats fed a diet enriched with coconut oil had lower soluble enkephalinase activity than the group fed olive oil (p<0.01) and fish oil (p<0.05) whereas rats fed a diet enriched with fish oil had lower membrane-bound enkephalinase activity than the group fed with olive (p<0.001) or coconut oil (p<0.05). Significant negative correlations were observed between certain fatty acids and enkephalinase activities in the groups fed with olive and coconut oils. No correlations were observed in the group fed with fish oil. Conclusions. Dietary fat modifies enkephalinase activity in the frontal cortex depending on the degree of saturation of the used oil. It is postulated that the functions, in which enkephalins are involved, such as pain modulation or cognitive functions, may also be affected according to the type of oil used in the diet.
... Finally they were sacrificed by perfusing them through the same ventricle with saline solution [12]. Insulin, fasting glucose, triglycerides, total cholesterol, and HDL were measured as previously reported [12,22,23]. Leptin and ghrelin concentrations in plasma were also determined as previously reported [12,24]. ...
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Extra virgin olive oil (EVOO) has been reported to have a distinct influence on gut microbiota in comparison to other fats, with its physiological benefits widely studied. However, a large proportion of the population consumes olive oil after a depurative process that not only mellows its taste, but also deprives it of polyphenols and other minority components. In this study, we compare the influence on the intestinal microbiota of a diet high in this refined olive oil (ROO) with other fat-enriched diets. Swiss Webster mice were fed standard or a high-fat diet enriched with EVOO, ROO, or butter (BT). Physiological parameters were also evaluated. At the end of the feeding period, DNA was extracted from feces and the 16S rRNA was pyrosequenced. The group fed ROO behaved differently to the EVOO group in half the families with statistically significant differences among the diets, with higher comparative levels in three families—Desulfovibrionaceae, Spiroplasmataceae, and Helicobacteraceae—correlating with total cholesterol. These results are again indicative of a link between specific diets, certain physiological parameters and the prevalence of some taxa, but also support the possibility that polyphenols and minor components of EVOO are involved in some of the proposed effects of this fat through the modulation of the intestinal microbiota
... Plasma was isolated by centrifugation of blood samples for 10 min at 2000 g, using heparin as anticoagulant, and stored at-20˚C. In plasma samples, insulin, fasting glucose, triglycerides, total cholesterol and HDL were determined as previously [49,50]. Plasma concentrations of leptin and ghrelin, were measured in a multianalyte profiling by using the Luminex-100 system and the XY Platform [51]. ...
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The type of fat in the diet determinates the characteristics of gut microbiota, exerting a major role in the development of metabolic syndrome. We hypothesize that a diet enriched with extra virgin olive oil (EVOO) has a distinctive effect on the intestinal microbiome in comparison with an enriched butter diet (BT) and this effect is related to the physiological benefits exerted by EVOO. Swiss Webster mice were fed standard (SD) or two high fat diets enriched with EVOO or butter. Hormonal, physiological and metabolic parameters were evaluated. At the end of the feeding period, DNA was extracted from faeces and the 16S rRNA genes were pyrosequenced. Among the main significant differences found, BT triggered the highest values of systolic blood pressure, correlating positively with the percentage of Desulfovibrio sequences in faeces, which in turn showed significantly higher values in BT than in EVOO. EVOO had the lowest values of plasmatic insulin, correlating inversely with Desulfovibrio, and had the lowest plasmatic values of leptin which correlated inversely with Sutterellaceae, Marispirillum and Mucilaginibacter dageonensis, the three showing significantly higher percentages in EVOO. The lowest total cholesterol levels in plasma were detected in SD, correlating positively with Prevotella and Fusicatenibacter, both taxa with significantly greater presence in SD. These results may be indicative of a link between specific diets, certain physiological parameters and the prevalence of some taxa, supporting the possibility that in some of the proposed effects of virgin olive oil the modulation of intestinal microbiota could be involved.
Male infertility has demonstrated to be a global health problem during last years. In this context, environmental contaminants and lifestyle mainly diet play an important role at the same time that provides an opportunity to develop new prevention strategies. It is well stablished that diet rich in raw vegetables and fruit, similar to Mediterranean diet, could play a beneficial effect on spermatogenesis and reproductive function related to a high intake of antioxidants. In fact, the main cause of infertility in men is due to direct damage of reactive oxygen species at the nucleus and mitochondria DNA, and the lipid peroxidation in the membrane of the sperm. On the other hand, Western diet has demonstrated to exert a negative impact on male fertility, as it is usually rich in saturated fatty acids and cholesterol. The changes in plasmatic lipid profile and the increase of cholesterol correlate with less sperm functionality. Virgin olive oil, the major lipid source in the Mediterranean diet, provide a high amount of antioxidant, mainly polyphenols and others minors components, together a beneficial lipid composition, characterized by the contribution of monounsaturated fatty acids. Besides that, compared with others dietary fats, virgin olive oil presents a particular effect on several peptidases activities in testis, and these results seem to be related to changes in plasma lipid profile. Changes in angiotensinase activities in testis are able to modulate local renin–angiotensin system, with relevant functions in male fertility.
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In order to study the mechanism by which increasing unsaturation of dietary fat lowers HDL-cholesterol levels, we studied various measures of HDL metabolism in hamsters fed with fats with different degrees of saturation. Hamsters were fed on a cholesterol-enriched (1 g/kg) semipurified diet containing 200 g/kg of maize oil, olive oil, or palm oil for 9 weeks. Increasing saturation of dietary fat resulted in increasing concentrations of total plasma cholesterol (4.29 (SD 0.51), 5.30 (SD 0.67) and 5.58 (SD 0.76) mmol/l respectively, n 12) and HDL-cholesterol (3.31 (SD 0.50), 3.91 (SD 0.12) and 3.97 (SD 0.43) mmol/l) and these concentrations were significantly higher (P < 0.05) in the palm-oil and olive-oil-fed hamsters compared with the maize-oil group. Total plasma triacylglycerol levels also increased with increasing fat saturation (1.01 (SD 0.59), 1.56 (SD 0.65) and 2.75 (SD 1.03) mmol/l) and were significantly higher (P < 0.05) in the palm-oil group compared with the olive-oil and maize-oil-fed hamsters. The three diets did not have differential effects on plasma activity levels of lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP). Levels of phospholipid transfer protein (PLTP) tended to be higher with increasing fat saturation but this effect was not significant. The capacity of liver membranes to bind human HDL3 was significantly higher (P < 0.05) in the hamsters fed with maize oil (810 (SD 100) ng HDL3 protein/mg membrane protein, n 4) compared with those fed on palm oil (655 (SD 56) ng/mg), whereas the olive-oil group had intermediate values (674 (SD 26) ng/mg). The affinity of HDL3 for the binding sites was not affected by the type of dietary fat. Hepatic lipase (EC activity, measured in liver homogenates, increased with increasing fat saturation. We conclude that dietary maize oil, when compared with either olive oil or palm-oil, may lower HDL-cholesterol concentrations by enhancing HDL binding to liver membranes.
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Thyroid disorders affect renal function, which involves changes in local renin angiotensin system (RAS). Angiotensin peptide levels in the tissue are regulated by the activity of several aminopeptidases (AP) known as angiotensinases. The nature and consequences of the thyroid-induced RAS changes are not completely understood. We investigated the relationship between thyroid status (hyper- and hypothyroidism) and several kidney AP actions involved in RAS control. We have determined fluorometrically soluble (SOL) and membrane-bound (M-B) alanylaminopeptidase (AlaAP), glutamylaminopeptidase (GluAP) and aspartylaminopeptidase (AspAP) activity using naphthylamide derivatives as substrates. Sprague-Dawley rats were divided into three groups--control, hyperthyroid, and hypothyroid. Hyperthyroidism was induced by daily subcutaneous injection of L-thyroxin (300 microg/kg/day). Hypothyroidism was induced by continuous administration of methimazole (0.03%) in drinking water. Hypothyroid animals demonstrated a significant increase in SOL and M-B GluAP activity in renal cortex and a decrease in M-B AlaAP compared to euthyroid rats. This result may suggest higher Ang III availability. In hyperthyroid animals, M-B AlaAP and M-B AspAP activity increased significantly, which may suggest increased Ang III to Ang IV metabolism and greater formation of Ang 2-10, respectively. In contrast, no differences were observed between euthyroid and hypothyroid animals for SOL and M-B AP activity in renal medulla. However, hyperthyroid animals demonstrated a significant decrease in SOL and M-B GluAP activity compared to euthyroid rats, which may suggest a greater availability of Ang II in renal medulla. Alterations in angiotensin metabolism may, in part, account for some changes in renal function during thyroid disorders.
We have analyzed the fatty acid composition of subcutaneous fat in the Iberian pork feed with acorns using gas chromatography. We have found a 59.1% content in oleic acid (18:1) and 62% of total monounsaturated fatty acids. This figures statistically does differs from the data about fat composition in pig taken from others food composition sources. We conclude that Iberian pork feed with acorns have a very high content in monounsaturated fatty acids and can no be considered as harmful as other animals fats.
The effects of dietary fat saturation on eicosanoid urinary excretion, platelet aggregation (PA) and blood pressure (BP) were studied in 42 healthy subjects. They consumed four consecutive diets differing in their fat saturation [saturated (SFA); monounsaturated (MUFA); polyunsaturated n-6 (PUFA n-6); and polyunsaturated n-6/n-3, (PUFA n-3)]. Each diet period lasted 5 weeks. There were no differences in 24-h 2,3-dinor-6- keto-prostaglandin F1 alpha excretion among dietary periods. A significant effect was noted regarding the excretion of 11-dehydro-thromboxane B2 (P < 0.0001). During the PUFA n-6 phase the excretion was significantly higher than during SFA and MUFA periods. Dietary fatty acid composition had a significant effect on ADP (1 mumolL-1) and collagen (2 mgL-1) induced PA. Dietary fat also had a significant effect on systolic and diastolic blood pressure (P < 0.0001). Both were significantly higher during the SFA period than during the other three periods. Our findings suggest that changes in dietary fatty acids may have mild, but significant, effects on eicosanoid production, platelet aggregation and blood pressure.
We studied the possible existence of physiological sex differences in serum aminopeptidase activities in mice, by evaluating the effect of gonadectomy and the in vitro response to the presence in the medium of cholesterol or steroid hormones. Alanyl- and glutamyl-aminopeptidase activities were measured in sera from male, female, orchiectomized and ovariectomized mice, incubated with substrate solutions, and compared with the same groups of serum incubated with substrate solutions including cholesterol, 17-beta-estradiol, testosterone, progesterone or hydrocortisone. Our results demonstrated highly significant sex differences, and an influence of cholesterol and steroid hormones on aminopeptidase activity. Depending on the nature of the aminopeptidase, these enzymes responded in different ways to the presence of these substances and also responded differently to gonadectomy. For alanyl-aminopeptidase activity, but not for glutamyl-aminopeptidase activity, there was a clear difference in response between males and females to incubation of the serum with steroid hormones.
Valsartan, a selective antagonist of angiotensin II at the AT(1) receptor subtype, is an efficacious, orally active, blood pressure-lowering agent used in hypertensive patients. Given that aminopeptidases (APs) play a major role in the metabolism of local peptides involved in blood pressure control, studying them helped us to understand cardiovascular control. We studied the effect of valsartan on angiotensin II- (GluAP) and vasopressin- (CysAP) degrading activities in the kidney in the rat model of renovascular hypertension, Goldblatt two-kidney one-clip. GluAP and CysAP in renal cortex and medulla exhibited different responses to hypertension and valsartan treatment. In the renal cortex, GluAP decreased in clipped and non-clipped kidneys of hypertensive animals. However, while hypertension did not affect GluAP in the clipped kidney medulla, the non-clipped kidney exhibited an increase in soluble and a decrease in membrane-bound activity. Valsartan decreased soluble GluAP in the medulla of normotensive and hypertensive animals. In the renal cortex, CysAP activity was mainly downregulated following hypertension. Valsartan decreased soluble CysAP activity in sham-operated, but not in hypertensive animals. The renal medulla showed a significant valsartan-related decreased activity in clipped and non-clipped kidneys of both sham-operated and hypertensive animals. These results suggest a functional relationship between the AT(1) receptor and vasopressin-degrading activity.
The autocrine/paracrine control mechanisms of local factors, such as the renin-angiotensin system and the thyrotropin-releasing hormone (TRH), seem to play a relevant role in testicular physiology. It has been proposed that dietary fat composition influences male reproductive function modifying the cholesterol-phospholipid composition of testicular plasma membranes. Modifications in the composition and physical properties of the membranes may lead to alterations in the activities of membrane-bound (M-B) enzymes. We have previously demonstrated that cholesterol and steroid hormones affect aminopeptidase (AP) activities. Dietary fatty acids with different degrees of saturation modified AP activities in the serum of mice and an olive oil supplemented diet influenced the AP activities in the testes of mice. We hypothesized that the modification of dietary fat composition may affect angiotensin- [glutamyl-AP (GluAP), aspartyl-AP (AspAP)] and TRH- [pyroglutamyl-AP (pGluAP)] degrading activities in the testis. In this study, we investigated the effect of diets supplemented with sunflower oil (SFO), fish oil (FO), olive oil (OO), lard (L) or coconut oil (CO) on soluble (Sol) and M-B GluAP, AspAP and pGluAP in mice testis, using arylamides as substrates. Sol GluAP activity did not show differences among groups. However, Sol AspAP and Sol pGluAP progressively decreased with the degree of saturation of the fatty acid used in the diet. In contrast, M-B GluAP progressively increased with the degree of saturation of the fatty acid used in the diet. For M-B AspAP activity, mice fed diets containing FO showed significantly higher levels than those fed diets containing SFO, OO and L but not those containing CO. For M-B pGluAP activity, the highest levels were observed for mice fed diets containing FO and OO. The present data suggest that the type of fat used in the diet may influence the autocrine/paracrine functions of locally synthesized angiotensin peptides and TRH in the testis, and consequently may be important in male reproductive functions.
The greater incidence of hypertension in men and postmenopausal women compared with premenopausal women has suggested gender differences in vascular function. Vascular effects of the female sex hormones estrogen and progesterone and the male hormone testosterone have been described. Sex steroid receptors have been identified in vascular endothelium and smooth muscle. Interaction of sex hormones with cytosolic/nuclear receptors initiates long-term genomic effects that stimulate endothelial cell growth but inhibit smooth muscle proliferation. Activation of sex hormone receptors on the plasma membrane triggers nongenomic effects that stimulate endothelium-dependent vascular relaxation via NO-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Sex hormones also cause endothelium-independent inhibition of vascular smooth muscle contraction, [Ca2+]i, and protein kinase C. These vasorelaxant/vasodilator effects suggested vascular benefits of hormone replacement therapy (HRT) during natural and surgically induced deficiencies of gonadal hormones. Although some clinical trials showed minimal benefits of HRT in postmenopausal hypertension, the lack of effect should not be generalized because it could be related to the type/dose of sex hormone, subjects' age, and other cardiovascular conditions. The prospect of HRT relies on continued investigation of the molecular mechanisms underlying the vascular effects of sex hormones and identification of compounds that specifically target the vascular sex hormone receptors. Naturally occurring hormones and phytoestrogens may be more beneficial HRT than synthesized compounds. Also, the type/dose, time of initiation, and duration of HRT should be customized depending on the subject's age and preexisting cardiovascular condition, and thereby enhance the outlook of sex hormones as potential modulators of vascular function in hypertension.
Epidemiologic data from the Framingham Study provide insights into the population burden of heart failure (CHF), its prognosis and modifiable risk factors that promote it. In the general population CHF is chiefly the end stage of hypertensive, coronary and valvular cardiovascular disease. It is a major and growing problem in most affluent countries because of aging populations of increased size, and the prolongation of the lives of cardiac patients by modern therapy. Once clinically manifest, CHF, despite recent innovations in therapy, carries an unacceptably high mortality rate. In the Framingham Study, median survival is only 1.7 y for men and 3.2 y for women, with only 25% of men and 38% of women surviving 5 y. This is a mortality rate 4-8 times that of the general population of the same age. This poor outlook is observed for all etiologies of CHF and sudden death is a prominent feature of the mortality. Based on population attributable risks, hypertension has the greatest impact, accounting for 39% of CHF events in men and 59% in women. Despite its much lower prevalence in the population (3-10%) myocardial infarction also has a high attributable risk in men (34%) and women (13%). Valvular heart disease only accounted for 7-8% of CHF. Hypertension increased the age and risk factor adjusted hazard of CHF 2-fold in men and 3-fold in women, with a greater impact of the systolic than diastolic blood pressure. Diabetes increased CHF risk 2-8 fold with risk ratios twice as large in women as men. About 19% of CHF cases have diabetes. It accounted for 6-12% of the CHF in the Framingham Study cohort. Dyslipidemia characterized by a high total/HDL cholesterol ratio, but not the total cholesterol alone was a risk factor for CHF. An enlarged heart on X-Ray, ECG-LVH, a reduced vital capacity and rapid heart rate usually signified deteriorating cardiac function. CHF risk associated with ECG-LVH was independent of X-Ray cardiomegaly but risk was further augmented when both coexist. Echocardiographic left ventricular hypertrophy signifies a high risk of CHF proportional to the degree of increase in left ventricular mass without a critical value that delineates compensatory from pathological hypertrophy. Risk of CHF in persons predisposed by hypertension, diabetes or cardiac conditions varies over a 10-fold range depending on the aforementioned modifiable risk factors and indicators of deteriorating left ventricular function. Using multivariate risk formulations it is possible to identify 20% of the population from which 70% of the CHF will evolve. Those in the upper quintile of multivariate risk are good candidates for echocardiographic testing to delineate those needing aggressive preventive measures to delay the onset of CHF. Therapy of CHF must begin with treatment of presymptomatic left ventricular dysfunction to reverse the dysfunctional maladaptive changes.
The action of testosterone on the 45Ca2+ uptake and insulin secretion was studied in short-term experiments using isolated pancreatic islets of Langerhans. Testosterone (1 microM) stimulated 45Ca2+ uptake within 60 seconds of incubation on similar proportion than tolbutamide. Also, the hormone rapidly increased insulin release (34%; 180 seconds) on the presence of non-stimulatory concentrations of glucose (3 mM). Impermeant testosterone-BSA significantly stimulated the secretion of insulin to a lower percentage (10%). The action of the hormone is specific--neither 17beta-E2 nor progesterone stimulated insulin secretion in the presence of 3 mM glucose. The action of testosterone on insulin secretion was dose-dependent, and at rat plasma physiological concentrations (25 nM), stimulus was 17% (p < 0.05). In conclusion, in isolated pancreatic islets experiments, physiological concentration of testosterone rapidly stimulate insulin secretion and 45Ca2+ uptake through a membrane bound mechanism.