Omega-3 fatty acids and metabolic syndrome: Effects and emerging mechanisms of action

The history of research into the relationship between dietary fat intake and impaired insulin action has its origin in the work of Himsworth approximately 60 years ago [1, 2]. In a series of pioneering studies using crude indices of insulin action and limited subject numbers (only one in an often quoted paper!), Himsworth linked high levels of fat intake with insulin resistance, and conversely, improved insulin action with predominantly carbohydrate diet. However, the link was tenuous and really apparent only at the extreme ends of the dietary spectrum (<20 or > 80 % of calories as fat). These studies, flawed as they were, influenced the field enormously in the absence of any significant work in the area for a remarkable period of time. The conclusions reached by Himsworth were reinforced to some extent by misuse of glucose tolerance data that showed deteriorations following periods on diets extremely low in carbohydrate (< 50 g/day) and improvement on liquid formula diets providing a remarkably high percentage (75-85 %) of calories from carbohydrate [3-5]. It was really not until the 1980 s that the development of acceptable techniques for the measurement of insulin action in vivo allowed the relationship between dietary fat intake and insulin action to be accurately assessed. These studies have essentially been confined to investigations in rodents and humans.

Dietary fats and insulin action

Recent data indicate that peripheral insulin sensitivity may be influenced by dietary fat quality and skeletal muscle phospholipid fatty acid composition. During a health survey of 70-year-old men insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp technique and the fatty acid composition of the serum cholesterol esters was determined (n=215) by gas liquid chromatography. In a subsample the fatty acids of the skeletal muscle phospholipids and triglycerides were determined after fine needle biopsy from m. vastus lateralis (n=39). The peripheral insulin sensitivity was significantly and negatively correlated to the proportion of palmitic (r=−0.31, p<0.001), palmitoleic (r=−0.25, p<0.001) and di-homo-γ-linolenic (r=−0.33, p<0.001) acids and positively to the content of linoleic (r=0.28, p<0.001) acid in the serum cholesterol esters. There was an even stronger negative relationship to the proportion of palmitic acid in the skeletal muscle phospholipds (r=−0.45, p<0.004). The fatty acid composition was also significantly related to insulin sensitivity in a stepwise multiple regression analysis in the presence of other clinical variables, which were associated with insulin action in univariate analysis. Thus, more than 51% of the variation of the insulin sensitivity was explained by an equation containing body mass index, serum triglyceride concentration and the content of palmitic acid in the skeletal muscle phospholipids. It is concluded that the fatty acid composition in serum and of the phospholipids of skeletal muscle may influence insulin action in elderly men.

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Insulin sensitivity is related to the fatty acid composition of serum lipids and skeletal muscle phospholipids in 70-year-old men.

Aims/hypothesis
Inflammatory alterations in white adipose tissue appear to underlie complications of obesity including diabetes mellitus Polyunsaturated fatty acids (PUFA), particularly those of the n−3 series, modulate immune responses and may ameliorate insulin sensitivity In this study, we investigated how PUFA affect white adipose tissue inflammation and gene expression in obese diabetic animals

https://link.springer.com/content/pdf/10.1007%2Fs00125-006-0300-x.pdf

Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids.

OBJECTIVE Hypertriglyceridemia is associated with cardiovascular disease in diabetes. Fibrates effectively lower, but do not always normalize, serum triglyceride levels. Fish oil supplements may then be added to lower serum triglyceride levels. Doubt remains whether the net effect of fish oil intake on glycemic control is beneficial in diabetes. We therefore performed a meta-analysis from published clinical trials. RESEARCH DESIGN AND METHODS Data sources were Medline (Cologne, Germany), Excerpta Medica, Current Contents, review articles, and published reference lists. Publications of 26 trials were selected, and all trials included more than five diabetes (IDDM and NIDDM) patients and addressed the effects offish oil (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) on serum lipids and glucose tolerance. We (C.E.F, M.J.F.M.J.) extracted data independently based on predetermined criteria. Studies were classified according to design. RESULTS All studies combined showed a decrease in mean triglyceride concentrations in association with fish oil: −0.60 mmol/1 (95% CI, −0.84 to −0.33, P P = 0.01), with both findings most prominent in NIDDM. No significant changes in HbA 1c percentages occurred in diabetic subjects treated with fish oil. Fasting blood glucose levels were increased with borderline significance in NIDDM subjects (0.43 mmol/1 [95% CI, 0.00–0.87], P = 0.06) and were significantly lower in IDDM subjects (−1.86 mmol/1 [95% CI, −3.1 to −0.61], P 1c and triglycerides and of DHA (g/day) on fasting blood glucose levels, HbA 1c , and triglycerides were demonstrated only in NIDDM subjects. CONCLUSIONS The use of fish oil has no adverse affects on HbA 1c in diabetic subjects and lowers triglyceride levels effectively by almost 30%. However, this may be accompanied by a slight increase in LDL cholesterol concentration. Fish oil may be useful in treating dyslipidemia in diabetes.

Fish Oil and Glycemic Control in Diabetes: A meta-analysis

To determine the impact of fish-oil supplementation on glucose and lipid metabolism in patients with impaired glucose tolerance (IGT), 30 ml fish oil containing 3.8 g eicosapentaenoic acid (EPA; 20:5 ω 3) and 2.5 g docosahexaenoic acid (DHA; 22:5 ω 3) were given to eight obese subjects with IGT (mean ± SD age 50.3 ± 8.0 yr) in addition to their regular diet for 2 wk. Studies were performed in randomized order versus an isocaloric control period with a washout phase of 3 wk. Hyperinsulinemic clamp examinations (1 and 10 mU · kg −1 · min −1 ) were performed. Glucose disposal rate (M value) rose from basal 14.3 ± 5.1 to 17.9 ± 4.4 μmol · kg −1 · min −1 after fish oil ( P −1 · min −1 ; with fish oil, 45.1 ± 9.8 μmol · kg −1 · min −1 ;NS). Basal hepatic glucose output remained unaffected by fish oil, whereas fractional glucose clearance after intravenous glucose loading (2.4 mmol/kg body wt, t = 30 min) tended to increase ( K value: without fish oil, 2.15 ± 1.02%/min; with fish oil, 2.74 ± 1.26%/min; NS). Neither the fasting concentrations of glucose and insulin nor induced glycemia and insulin response during intravenous glucose loading calculated as incremental area under the curve changed after fish-oil supplementation. Supplementation of ω-3 fatty acids led to a mean decrease in total cholesterol of 15.2% (5.78 ± 1.19 to 4.90 ± 0.83 mM, P P P P

Wolf Osterrode

Papers

Metabolic effects of fish-oil supplementation in patients with impaired glucose tolerance.