Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

Abstract

Aims/hypothesis Calorie restriction is an essential component in the treatment of obesity and associated diseases. Longchain n-3 polyunsaturated fatty acids (LC n-3 PUFA) act as natural hypolipidaemics, reduce the risk of cardiovascular disease and could prevent the development of obesity and insulin resistance. We aimed to characterise the effectiveness and underlying mechanisms of the combination treatment with LC n-3 PUFA and 10% calorie restriction in the prevention of obesity and associated disorders in mice. Methods Male mice (C57BL/6J) were habituated to a cornoil-based high-fat diet (cHF) for 2 weeks and then randomly assigned to various dietary treatments for 5 weeks or 15 weeks: (1) cHF, ad libitum; (2) cHF with LC n-3 PUFA concentrate replacing 15% (wt/wt) of dietary lipids (cHF+F), ad libitum; (3) cHF with calorie restriction (CR; cHF+CR); and (4) cHF+F+CR. Mice fed a chow diet were also studied. Results We show that white adipose tissue plays an active role in the amelioration of obesity and the improvement of glucose homeostasis by combining LC n-3 PUFA intake and calorie restriction in cHF-fed mice. Specifically in the epididymal fat in the abdomen, but not in other fat depots, synergistic induction of mitochondrial oxidative capacity and lipid catabolism was observed, resulting in increased oxidation of metabolic fuels in the absence of mitochondrial uncoupling, while low-grade inflammation was suppressed, reflecting changes in tissue levels of anti-inflammatory lipid mediators, namely 15-deoxy-Δ 12,15 -prostaglandin J 2 and protectin D1. Conclusions/interpretation White adipose tissue metabolism linked to its inflammatory status in obesity could be modulated by combination treatment using calorie restriction and dietary LC n-3 PUFA to improve therapeutic strategies for metabolic syndrome.

Eicosapentaenoic acid promotes thermogenic and fatty acid storage capacity in mouse subcutaneous adipocytes

“…Consistently, changes in ACCa and CPT1 expression, along with increased AMPK phosphorylation, suggest that FA oxidation is enhanced in EPAtreated adipocytes. Our results are in agreement with the previous reports that mice fed a diet rich in DHA and EPA had enhanced FA oxidation and mitochondrial function in adipose tissue [33]. Additionally, our result of glucose metabolism implies that EPA enhances glucose oxidation, which may result from the improved mitochondrial oxidation.…”

Brown adipose tissue dynamics in wild-type and UCP1-knockout mice: in vivo insights with magnetic resonance

“…Recently it has been demonstrated that the respiratory capacity of white adipose tissue, and potentially also of BAT, may be enhanced by the presence of n-3 polyunsaturated fatty acids in the absence of UCP1 ( 79,80 ). This increased turnover of n-3 polyunsaturated fatty acids could not be corroborated in our study, as the saturation index of BAT lipids did not change during NST.…”

Mitochondrial Plasticity in Obesity and Diabetes Mellitus

“…dose-dependently protected from palmitate-induced inhibition of insulin signaling and induction of ROS production in rat hepatocytes (49). Combining HFD enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) and caloric restriction resulted in synergistic increase in mitochondrial oxidative capacity and lipid catabolism in adipocytes of mice (19). Eicosapentaenoic fatty acid rescued impaired mitochondrial oxidative capacity in LPL-deficient myotubes, probably via PPAR-d-mediated activation of mitochondrial biogenesis (46).…”