Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse

Healthy Living Research and Development, Ross Products Division, Abbott Laboratories, Columbus, OH 43215, USA.
Metabolism (Impact Factor: 3.89). 11/2006; 55(10):1365-74. DOI: 10.1016/j.metabol.2006.06.007
Source: PubMed


Diets rich in monounsaturated fatty acids (MUFA) are recommended for individuals with type 2 diabetes mellitus (T2DM). The American Heart Association recommends increasing intakes of n-3 polyunsaturated fatty acids (PUFA) to reduce the risk of vascular disease in high-risk individuals; however, the long-term effects of these bioactive fatty acids on glucose metabolism in insulin resistance are controversial. The present studies were conducted to evaluate the effects of diets rich in both MUFA and alpha linolenic acid (C18:3n-3, ALA), eicosapentaenoic acid (C20:5n-3, EPA), or docosahexaenoic acid (C22:6n-3, DHA), on glycemic control and other parameters related to vascular health in a mouse model of T2DM and insulin resistance. Male ob/ob mice (n = 15 per treatment) were fed 1 of 4 lipid-modified formula diets (LFDs) for 4 weeks: (1) MUFA control, (2) ALA blend, (3) EPA blend, and (4) DHA blend. A portion of a MUFA-rich lipid blend in the control LFD was replaced with 11% to 14% energy as n-3 PUFA. After 4 weeks, plasma glucose response to a standard meal (1.5 g carbohydrate/kg body weight) and insulin challenge (2 U/kg body weight, IP) was assessed, and samples were collected for analysis of glucose, insulin, and lipids. Vascular reactivity of isolated aortic rings was assessed in an identical follow-up study. The results showed that insulin-resistant mice fed an LFD with EPA and/or DHA blends had significantly (P < .05) lower triglycerides and free fatty acids, but insulin sensitivity and fasting plasma glucose were not improved. However, mice fed with the ALA blend had significantly improved insulin sensitivity when compared to those fed with other LFD (P < .05). Animals fed an LFD with n-3 PUFA from marine or plant sources showed significantly improved vascular responses as compared with the MUFA-rich LFD (E(max), P < .05) and ob/ob reference mice consuming chow (E(max) and pEC(50), P < .05). In summary, long-term consumption of LFD with n-3 PUFAs improved blood lipids and vascular function in an animal model of insulin resistance and T2DM; however, only MUFA-rich LFD with ALA also improved both insulin sensitivity and glycemic responses. Further studies of MUFA-rich LFD with ALA with individuals who have T2DM are warranted.

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    • "Lankinen et al. suggested that PUFA-related diet may have a beneficial effect to prevent high risk persons from getting type II DM 12. In the animal model of vascular response and insulin resistance, PUFA can reduce vascular complications and improve the phenomenon of insulin-resistance 13. Another study of animal model for PUFA in type II DM also found that PUFA could reduce insulin resistance and increase insulin sensitivity due to increased adiponectin and decreased tumor necrosis factor-alpha in plasma. "
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    ABSTRACT: Objective: This is an Asian study, which was designed to examine the correlations between biochemical data and food composition of diabetic patients in Taiwan. Methods: One hundred and seventy Taiwanese diabetic patients were enrolled. The correlations between biochemical data and diet composition (from 24-hour recall of intake food) of these patients were explored (Spearman correlation, p < 0.05). Diet components were also correlated with each other to show diet characteristics of diabetic patients in Taiwan. Linear regression was also performed for the significantly correlated groups to estimate possible impacts from diet composition to biochemical data. Results: Postprandial serum glucose level was negatively correlated with fat percentage of diet, intake amount of polyunsaturated fatty acid and fiber diet composition. Hemoglobin A1c was negatively correlated with fat diet, polyunsaturated fatty acid and vegetable diet. Fat composition, calorie percentage accounted by polyunsaturated fatty acid and monounsaturated fatty acid in diet seemed to be negatively correlated with sugar percentage of diet and positively correlated with vegetable and fiber composition of diet. Linear regression showed that intake amount of polyunsaturated fatty acid, calorie percentage accounted by polyunsaturated fatty acid, fat percentage of diet, vegetable composition of diet would predict lower hemoglobin A1c and postprandial blood sugar. Besides, higher percentage of fat diet composition could predict higher percentage of vegetable diet composition in Taiwanese diabetic patients. Conclusion: Fat diet might not elevate serum glucose. Vegetable diet and polyunsaturated fatty acid diet composition might be correlated with better sugar control in Taiwanese diabetic patients.
    International journal of medical sciences 03/2014; 11(5):515-21. DOI:10.7150/ijms.8158 · 2.00 Impact Factor
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    • "Unsaturated fatty acids may rescue the detrimental metabolic effects associated with saturated fatty acid treatment alone [9]. Of particular interest are the long chain omega-3 (n-3) polyunsaturated FA (PUFA), such as docosahexaenoic acid (DHA) which attenuate the reductions in insulin sensitivity caused by excessive lipids [7, 8, 10] and sucrose [13–15] in cells [7], metabolically normal [10, 11, 16, 17], obese [12], and insulin-resistant animals [13–15]. Omega PUFAs partition fatty acids toward oxidation [18], which may provide a mechanism to improve insulin sensitivity by promoting skeletal muscle fatty acid oxidation and reducing intramyocellular lipid content. "
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    ABSTRACT: Background. Accumulation of free fatty acids leads to lipid-toxicity-associated skeletal muscle atrophy. Palmitate treatment reduces myoblast and myotube growth and causes apoptosis in vitro. It is not known if omega-3 fatty acids will protect muscle cells against palmitate toxicity. Therefore, we examined the effects of docosahexaenoic acid (DHA) on skeletal muscle growth. Methods. Mouse myoblasts (C2C12) were differentiated to myotubes, and then treated with 0 or 0.5 mM palmitic acid or 0 or 0.1 mM DHA. Results. Intramyocellular lipid was increased in palmitate-treated cells but was prevented by DHA-palmitate cotreatment. Total AMPK increased in DHA+ palmitate-treated compared to palmitate only cells. RpS6 phosphorylation decreased after palmitate (-55%) and this was blunted by DHA+ palmitate (-35%) treatment. Palmitate treatment decreased PGC1α protein expression by 69%, but was increased 165% with DHA+ palmitate (P = 0.017) versus palmitate alone. While palmitate induced 25% and 90% atrophy in myotubes (after 48 hours and 96 hours, resp.), DHA+ palmitate treatment caused myotube hypertrophy of ~50% and 100% after 48 and 96 hours, respectively. Conclusion. These data show that DHA is protective against palmitate-induced atrophy. Although DHA did not activate the AMPK pathway, DHA treatment restored growth-signaling (i.e., rpS6) and rescued palmitate-induced muscle atrophy.
    09/2012; 2012(10):647348. DOI:10.5402/2012/647348
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    • "Nevertheless, among all rats plasma DHA and AA levels were inversely correlated with the plasma 18:1/18:0 ratio as well as TG and glucose levels, suggesting that PUFAs have antagonistic effects on Scd1 activity. It will be of interest to determine whether reductions in Scd1 activity mediate decreases in TG and/or glucose levels in response to omega-3 fatty acid supplementation in rodent disease models (Hassanali et al., 2010; Lu et al., 2011; Mustad et al., 2006) and in schizophrenic patients treated with atypical antipsychotic medications (Caniato et al., 2006; Peet et al., 2002). Nevertheless, these data highlight an important contribution of PUFAs to antipsychotic effects on Scd1 expression/ activity, and emphasize the need to account for PUFAs in future antipsychotic studies. "
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    ABSTRACT: Recent preclinical and clinical evidence suggests that the stearoyl-CoA desaturase-1 (Scd1) enzyme plays a key role in the regulation of triglyceride (TG) biosynthesis and insulin sensitivity, and in vitro studies have found that antipsychotic medications up-regulate Scd1 mRNA expression. To investigate these effects in vivo, rats were treated with risperidone (1.5, 3, and 6mg/kg/d), paliperidone (1.5, 3, and 6mg/kg/d), olanzapine (2.5, 5, and 10mg/kg/d), quetiapine (5, 10, and 20mg/kg/d), haloperidol (1, and 3mg/kg/d) or vehicle through their drinking water for 40days. Effects on liver Scd1 mRNA expression and an index of Scd1 activity (the plasma 18:1/18:0 ratio, 'desaturation index') were determined, as were postprandial plasma triglyceride (TG), glucose, insulin, and polyunsaturated fatty acid (PUFA) levels. All atypical antipsychotics increased the plasma 18:1/18:0 ratio, but not liver Scd1 mRNA expression, at doses found to also increase plasma TG levels. Among all rats (n=122), the plasma 18:1/18:0 ratio accounted for 56% of the variance in TG concentrations. The plasma 18:1/18:0 ratio was also positively associated with erythrocyte and heart membrane phospholipid 18:1n-9 composition. All antipsychotics except risperidone increased glucose levels at specific doses, and none of the antipsychotics significantly altered insulin levels. The plasma 18:1/18:0 ratio accounted for 20% of the variance in glucose levels. Plasma omega-3 and omega-6 PUFA levels were inversely correlated with the plasma 18:1/18:0 ratio and TG and glucose levels. These in vivo data demonstrate that different atypical antipsychotic medications increase the plasma 18:1/18:0 ratio in association with elevations in postprandial TG and glucose levels, and that concomitant elevations in PUFA biosynthesis oppose these effects.
    Schizophrenia Research 06/2011; 129(1):66-73. DOI:10.1016/j.schres.2011.03.016 · 3.92 Impact Factor
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