Docosahexaenoic acid supplementation improved lipocentric but not glucocentric markers of insulin sensitivity in hypertriglyceridemic men.

Western Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, and Department of Nutrition, University of California, Davis, California 95616, USA.
Metabolic syndrome and related disorders (Impact Factor: 1.92). 02/2012; 10(1):32-8. DOI: 10.1089/met.2011.0081
Source: PubMed

ABSTRACT Increase in obesity and metabolic syndrome are associated with increases in insulin resistance (IR) and type 2 diabetes mellitus. Results from animal intervention studies and human epidemiological studies suggest that n-3 polyunsaturated fatty acids can prevent and reverse IR, but results from human intervention studies have varied. Results from some human and animal studies suggest that docosahexaenoic acid (22:6n-3; DHA) may be more effective than eicosapentaenoic acid (20:5n-3; EPA) in the prevention of IR.
By using a placebo-controlled, parallel study design, we examined the effects of DHA supplementation (3 grams/day, 90 days) in the absence of EPA on glucocentric and lipocentric markers of IR in hypertriglyceridemic men (n=14-17/group).
DHA supplementation increased fasting plasma glucose concentration by 4.7% (P<0.05), but did not alter other indices of IR based on fasting (insulin and homeostasis model assessment of insulin resistance [HOMA-IR]) or postprandial insulin and glucose concentrations (areas under curves for insulin and glucose, Matsuda index). Glucose increased by 2.7% in the placebo group and was not significant; increases in glucose in the two groups did not differ from each other. DHA decreased circulating concentrations of several lipocentric markers of IR, including plasma concentrations of nonesterified fatty acids (13.0%), small, dense low-density lipoprotein (LDL) particles (21.7%), and ratio of tryglycerides to high-density lipoprotein cholesterol (TG/HDL-C) (34.0%) (P<0.05). None of the variables changed in the placebo group.
Our results suggest that lipocentric markers of IR are more responsive to DHA supplementation than the glucocentric markers. Future studies with DHA in prediabetic subjects and direct measures of insulin sensitivity are needed.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Postprandial refers to diet induced changes in plasma concentrations of sugars, amino acids and fats between 0 and 6 h following a meal. This review details the fat transport through lipoprotein particles and triglyceride fractions in the postprandial plasma. The long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is more active in postprandial plasma and is more abundantly incorporated into the surface phospholipid fraction of lipoproteins. A survey of controlled clinical trials in the literature demonstrates that 1,000 mg to 2,000 mg DHA daily is effective to treat hypertriglyceridemia (HTG), mixed dyslipidemia and most effectively controls elevated postprandial triglycerides (TG). TG is a marker for total fat in circulation. Omega-3 fatty acids lower fasting and postprandial TG, an activity first discovered in 1971 in Greenlandic Inuits. Low TG and high DHA were coincident with the absence of type 2 diabetes. It is now known that DHA is the major structural and functional omega-3 component of lipoproteins in human plasma. DHA is the omega-3 to most substantially increase by mass in the phospholipid fraction of very low-density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL). DHA is most effective at raising HDL levels and improves the omega-3 index in red blood cells (RBC). DHA intake also correlates with greater than 25 % reductions of fasting TG and greater than 40 % reductions in postprandial TG. Postprandial HTG is common in the type 2 diabetes; therefore, we considered the safety of DHA from Schizochytrium sp. algae oil and the evidence for risk reduction of coronary vascular disease (CVD) and type 2 diabetes. Recent clinical trials suggest high DHA intake from Chromista algae controls plasma TG, but does not appear to control glucocentric markers or cholesterol levels. DHA directly affects postprandial TG transport, but has little effect on insulin function and insulin resistance. Applications for use in South Asian diabetics are considered. 1,200 mg algae DHA daily over 3 months is an optimized program for direct control of postprandial HTG and is safe for type 2 diabetics.
    International Journal of Diabetes in Developing Countries 06/2013; 33(2):75-82. DOI:10.1007/s13410-013-0125-3 · 0.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is associated with an overexpansion of adipose tissue, along with increases in blood pressure, glycemia, inflammation, and thrombosis. Research to develop nutritional interventions to prevent or treat obesity and its associated diseases is greatly needed. Previously, we demonstrated the ability of eicosapentaenoic acid (EPA) to prevent high-fat (HF) diet-induced obesity, insulin resistance, and inflammation in mice. The objective of the current study was to determine the mechanisms mediating the anti-inflammatory and antilipogenic actions of EPA. In a previous study, male C57BL/6J mice were fed a low-fat diet (10% of energy from fat), an HF diet (45% of energy from fat), or an HF diet supplemented with EPA (45% of energy from fat; 36 g/kg EPA; HF+EPA) for 11 wk or an HF diet for 6 wk and then switched to the HF+EPA diet for 5 wk. In this study, we used histology/immunohistochemistry, gene expression, and metabolomic analyses of white adipose tissue from these mice. In addition, cultured mouse 3T3-L1 adipocytes were treated with 100 μM EPA for 48 h and then used for extracellular flux assays with untreated 3T3-L1 adipocytes used as a control. Compared with the HF diet, the HF+EPA diet significantly reduced body weight, adiposity, adipocyte size, and macrophage infiltration into adipose tissue. No significant differences in overall body weight or fat pad weights were observed between HF-fed mice vs. those fed the HF+EPA diet for a short time after first inducing obesity with the HF diet. Interestingly, both histology and immunohistochemistry results showed a significantly lower mean adipocyte size and macrophage infiltration in mice fed the HF diet and then switched to the HF+EPA diet vs. those fed HF diets only. This indicated that EPA was able to prevent as well as reverse HF-diet-induced adipocyte inflammation and hypertrophy and that some of the metabolic effects of EPA were independent of body weight or adiposity. In addition, adipose tissue metabolomic data and cultured adipocyte extracellular flux bioenergetic assays indicated that EPA also regulated mitochondrial function by increasing fatty acid oxidation and oxygen consumption, respectively. With the use of mice and cultured adipocytes, we showed that EPA ameliorates HF-diet effects at least in part by increasing oxygen consumption and fatty acid oxidation and reducing adipocyte size, adipogenesis, and adipose tissue inflammation, independent of obesity. © 2015 American Society for Nutrition.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Consumption of fish oil-rich foods containing docosahexaenoic acid (DHA) can result in a low incidence of diabetes. The underlying mechanisms of these anti-hyperglycemic effects are ambiguous. This study aims to investigate the role of DHA in the prevention and treatment of type 1 diabetes in a murine model. Forty streptozotocin-induced diabetic mice were divided into control with diabetes, diabetes prevention (500 μg/kg DHA orally for 5 days) or diabetes treatment groups (DHA solvent in DMSO into the colon for 5 days). The groups were observed for 25 days after administration of DHA. Mice in the prevention and treatment group had shinier fur, increased body weight, significantly lower food and water intake and were more active compared with the control group with diabetes. Elevated insulin and liver SOD and T-AOC levels were also observed. Furthermore, islet cell apoptosis was reduced and islet cell GLP-1R expression increased.
    International Journal of Clinical and Experimental Medicine 01/2014; 7(9):3021-9. · 1.42 Impact Factor