Monounsaturated Fatty Acids in a High-Fat Diet and Niacin Protect from White Fat Dysfunction in the Metabolic Syndrome

Scope Obesity is a principal causative factor of metabolic syndrome. Niacin potently regulates lipid metabolism. Replacement of saturated fatty acids by MUFAs or inclusion of omega-3 long-chain PUFAs in the diet improves plasma lipid levels. However, the potential benefits of niacin in combination with MUFAs or omega-3 long-chain PUFAs against white adipose tissue (WAT) dysfunction in the high fat diet (HFD)-induced metabolic syndrome are unknown. Methods and results Male Lep(ob/ob)LDLR(-/-) mice are fed a chow diet or HFDs based on milk cream (21% kcal), olive oil (21% kcal), or olive oil (20% kcal) plus 1% kcal from eicosapentaenoic and docosahexaenoic acids, including immediate-release niacin (1% w/v) in drinking water, for 8 weeks. Mice are then phenotyped. Dietary MUFAs are identified as positive regulators of adipose NAD(+) signaling pathways by triggering NAD(+) biosynthesis via the salvage pathway. This coexists with overexpression of genes involved in recognition of NAD(+) and fatty acids, a surrounding lipid environment dominated by exogenous oleic acid and an alternatively activated macrophage profile, which culminate in a healthy expansion of WAT and improvement of several hallmarks that typify the metabolic syndrome. Conclusion Niacin in combination with dietary MUFAs can favor WAT homeostasis in the development of HFD-induced obesity and metabolic syndrome.