| First Author | Li J | Year | 2014 |
| Journal | Mol Endocrinol | Volume | 28 |
| Issue | 8 | Pages | 1316-28 |
| PubMed ID | 24978197 | Mgi Jnum | J:216236 |
| Mgi Id | MGI:5608543 | Doi | 10.1210/me.2014-1011 |
| Citation | Li J, et al. (2014) Endogenous omega-3 polyunsaturated fatty acid production confers resistance to obesity, dyslipidemia, and diabetes in mice. Mol Endocrinol 28(8):1316-28 |
| abstractText | Despite the well-documented health benefits of omega-3 polyunsaturated fatty acids (PUFAs), their use in clinical management of hyperglycemia and obesity has shown little success. To better define the mechanisms of omega-3 PUFAs in regulating energy balance and insulin sensitivity, we deployed a transgenic mouse model capable of endogenously producing omega-3 PUFAs while reducing omega-6 PUFAs owing to the expression of a Caenorhabditis elegans fat-1 gene encoding an omega-3 fatty acid desaturase. When challenged with high-fat diets, fat-1 mice strongly resisted obesity, diabetes, hypercholesterolemia, and hepatic steatosis. Endogenous elevation of omega-3 PUFAs and reduction of omega-6 PUFAs did not alter the amount of food intake but led to increased energy expenditure in the fat-1 mice. The requirements for the levels of omega-3 PUFAs as well as the omega-6/omega-3 ratios in controlling blood glucose and obesity are much more stringent than those in lipid metabolism. These metabolic phenotypes were accompanied by attenuation of the inflammatory state because tissue levels of prostaglandin E2, leukotriene B4, monocyte chemoattractant protein-1, and TNF-alpha were significantly decreased. TNF-alpha-induced nuclear factor-kappaB signaling was almost completely abolished. Consistent with the reduction in chronic inflammation and a significant increase in peroxisome proliferator-activated receptor-gamma activity in the fat-1 liver tissue, hepatic insulin signaling was sharply elevated. The activities of prolipogenic regulators, such as liver X receptor, stearoyl-CoA desaturase-1, and sterol regulatory element binding protein-1 were sharply decreased, whereas the activity of peroxisome proliferator-activated receptor-alpha, a nuclear receptor that facilitates lipid beta-oxidation, was markedly increased. Thus, endogenous conversion of omega-6 to omega-3 PUFAs via fat-1 strongly protects against obesity, diabetes, inflammation, and dyslipidemia and may represent a novel therapeutic modality to treat these prevalent disorders. |
