International Omega-3 Learning and Education Consortium for Health and Medicine

The obesity-associated metabolic syndrome epidemic is a significant health care concern today. The most recent study from the World Health Organization approximates that, globally, 1.6 billion adults are overweight with at least 400 million adults classified as obese ¹. Obesity is a major susceptibility factor leading to the development of various conditions of the metabolic syndrome. Chronic morbidities due to insulin resistance, hypertension, and dyslipidemia are metabolic abnormalities that are included in the disorder ². The association between excess body fat accumulation and the metabolic syndrome has been documented ³.

Adipose tissue, once considered a passive fuel reservoir, is now recognized as a dynamic endocrine organ that responds to traditional hormone systems and the central nervous system but also functions to secrete various hormones that regulate appetite and metabolism ⁴. Levels of the adipocyte-derived peptide hormone leptin are highly correlated with adipose tissue mass and are reduced in both humans and mice after weight loss ⁵. Obese humans and diet-induced obese mice were found to have higher levels of leptin as well. Elevated levels of plasma leptin are thought to occur because of blunted receptor sensitivity of the peptide hormone at the cellular level of adipose, analogous to the mechanism of insulin resistance ⁴. Peripheral and central administration of leptin leads to a reduction in food intake and body weight in diet-induced obese mice ⁶. These results introduced the idea that leptin increased satiety. In addition, other research indicates that adipocyte-derived free fatty acid levels in circulation are elevated in obese people with systemic insulin resistance ^7,8. These studies highlight the growing evidence that adipocyte secreted products are key constituents characterizing insulin resistance.

Oils from marine sources containing omega-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) have been shown to improve satiety in overweight and obese volunteers ⁹. Obese women with type-2 diabetes given a mixture of EPA and DHA for 2 months were found to have reduced markers for adiposity and atherogenic symptoms ¹⁰. To add to this, both total fat mass and adipocyte diameter from adipose tissue were significantly reduced with the omega-3 PUFA treatment. In a key study that compared calorie-restricted diets without any fish product to those containing fish or supplemental fish oil, it was found that weight loss was greater with the inclusion of either fish source ¹¹. Subjects in this study were young and overweight men whom were observed for a period of 8 weeks. These studies suggest that omega-3 PUFA appear to help reduce adipose stores and, ultimately, promote weight loss. However, it is not clear whether the mediation of fat loss from the intake of omega-3 PUFA was via increased ß-oxidation, improved satiety, or an alternative mechanism. Contrastingly, reports of no change in body fat for any intake of fish have also come to light ¹². Specific omega-3 PUFA content was not distinguished in this study. Although some research is encouraging, additional investigations must be conducted to determine the efficacy of omega-3 PUFA for reducing fat loss in the general population.

In regards to the pathogenesis of type-2 diabetes, endothelial dysfunction is a pronounced characteristic found in clinical patients ¹³. Supplementation of 1.2g/d of DHA for 6 weeks or 1.8g/d of EPA for 12 weeks showed a restoration and improvement in endothelial function in human subjects ^14,15. In contrast, the findings in another study in type-2 diabetic patients with hypertension revealed an increase in fasting glucose after consumption of EPA and DHA ¹⁶. This impairment of glycemic control could have been due to increased hepatic glucose output or unknown conflicting factors involved with hypertension. In addition, the study was conducted for only 6 weeks. Dietary PUFA represent a potential and practical approach in reducing obesity and the risk for type-2 diabetes. While the molecular mechanism remains to be elucidated, it can be theorized that omega-3 PUFA may suppress the formation of endoperoxides and inflammatory cytokines. This is accomplished by modifying the fatty acid composition of the phospholipid membrane. Thus, as omega-3 PUFA intake is increased, the dietary ratio of omega-6/omega-3 PUFA is lowered, which leads to a decrease in the incorporation of the omega-6 PUFA, such as arachidonic acid (AA), into membrane phospholipids. Furthermore, the activation of the lipid mediated signaling system, the endocannabinoid system, would be suppressed. The endocannabinoid signaling system has been associated with the dysregulation of triglycerides in adipose tissue, as observed in the obese ¹⁷. Since the primary receptor ligands involved in the activation of the system, anandamide and 2-arachidonoylglycerol, are derived from AA, a greater intake of omega-3 PUFA would reduce their synthesis as less AA is available for ligand formation.

With the growing trend of obesity, modern society faces an unmatched epidemic where the diseases associated with over-nutrition will surpass those for undernutrition as the primary cause of deaths in low-income communities ¹⁸. Omega-3 PUFA may serve as a potential prevention and treatment option for this growing concern.

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