• Obesity
• Cardiometabolic Disorder
• Inflammatory Disease

• Endocrinology
• Diabetes & Metabolic Syndrome
• Obesity
• Cardiometabolic Disorder
• Inflammatory Disease

Inflammation that develops in obese persons is thought to play an important role in the development of type 2 diabetes. Epidemiological and clinical data have shown that low levels of omega-3 polyunsaturated fat (PUFA) consumption is related to cardiovascular disease, and that a higher ratio of omega-6 PUFA to omega-3 PUFA consumption increases this risk. André Marette, PhD, Université Laval, Québec City, Québec, Canada, reviewed research from his group that explored whether omega-3 is a link between obesity and inflammation.

A mouse model (Fat-1) was developed in which inflammatory markers were significantly reduced, resulting in improvements in fasting insulin and insulin resistance (IR), and partial improvement in glucose tolerance [Kang JX et al. Nature 2004]. In addition, there was greater production of PD1, a molecule that decreases levels of inflammation in muscle, liver, and adipose tissue, and an improvement in IR when Fat-1 mice were fed a diet high in omega-3. This increase in PD1, 1 of several anti-inflammatory mediators, is thought to be an important mechanism by which omega-3 exerts its anti-inflammatory effects. Experiments using typical transcriptomic strategies in Fat-1 mice revealed changes in the regulation of cholesterol biosynthesis pathways, and prostaglandin synthesis and regulation, when omega-6 was increased and omega-3 was decreased in adipose tissue.

The lack of weight gain, despite adipogenesis, led to experiments that confirmed peroxisome proliferator activated receptor-gamma (PPAR-γ) was upregulated in adipose tissue in Fat-1 mice. PPAR-γ is known to contribute to regulation of adipogenesis. Remodeling of adipose tissue was also found in the Fat-1 mice. These mice had no increase in the overall amount of fat; however, they did have an increase in the number of adipocytes but these adipocytes were small. Because an increase in adipocyte size attracts macrophages and other immune cells in adipose tissue, this finding is considered to be important, said Prof. Marette.

Changes in the endocannabinoid signaling pathway were found in the Fat-1 mice with increased levels of omega-3 [Ge Q et al. Int J Obes (London) 2013]. This pathway comprises neuromodulatory lipids and receptors involved in appetite, among other processes. The cannabinoid CMR1 and CMR2 receptors were overexpressed, but interestingly the catabolic enzyme FAAH known to metabolize lipid molecules activating cannabinoid receptors, was reduced in adipose tissue. Increasing concentration of omega-3 in adipose tissue is thought to compete with omega-6 fatty acids, such as arachidonic acid, which are precursors of cannabinoid receptors, thus adipose tissue tries to increase the number of receptors and downregulates catabolic enzymes.

This reduction in endocannabinoid tone would explain improvements in inflammation and metabolic profiles in obese persons, perhaps through adiponectin production, he said. Further, their studies in Fat-1 mice have provided some understanding of the mechanisms through which omega-3 fatty acids control inflammation in the metabolic syndrome. Omega-3 fatty acids can activate resolution mediators to block inflammation, reduce endocannabinoid tone by competing with omega-6 fatty acids, and increase PPAR-γ. Together, these impact adipogenesis, insulin signaling, cholesterol biosynthesis, prostaglandin synthesis and regulation, and small ligand G-protein coupled receptors.

• © 2013 MD Conference Express®