A high-fat diet enriched with fish oil affects metabolic pathways in the hypothalamus of rats: a proteomic approach

Omega-3 fat is recognized as healthy, but its excess consumption may be harmful. We evaluated whether the long-term intake of a high-fat fish oil diet affects protein expression in the hypothalamus, a key site in energy homeostasis control. Male rats received either a control normolipidic or a high-fat fish oil diet for 8 weeks. Hypothalami were processed for proteomic analysis by LC-MS/MS. In total, 29 proteins were significantly altered in the fish group, of which 15 were down-regulated and 14 were up-regulated. Pathway-enrichment analysis, performed with the Panther platform, showed that 10 proteins were related to the “Metabolism of Carbohydrate” and “TCA Cycle and Respiratory Electron Transport” pathways. There were indications of pro-inflammatory activation and impairment of respiratory chain Complex 1 function, probably due to the excess fat content of the diet. Also, a protective role played by the type of fat was suggested by the findings, indicating a decrease in reactive oxygen species production, maintenance of NADH delivery to the respiratory chain, and production of anorexigenic signals. The chronic intake of a high-fat fish oil diet affected the expression of several hypothalamic proteins related to metabolic pathways. Although n-3 fat has recognized healthy properties, its excess consumption may lead to deleterious effects in the hypothalamus.