Cellular and molecular effects ofn−3 polyunsaturated fatty acids on adipose tissue biology and metabolism

Abstract

Adipose tissue and its secreted products, adipokines, have a major role in the development of obesity-associated metabolic derangements including Type 2 diabetes. Conversely, obesity and its metabolic sequelae may be counteracted by modulating metabolism and secretory functions of adipose tissue. LC-PUFAs (long-chain polyunsaturated fatty acids) of the n-3 series, namely DHA (docosahexaenoic acid; C(22:6n-3)) and EPA (eicosapentaenoic acid; C(20:5n-3)), exert numerous beneficial effects, such as improvements in lipid metabolism and prevention of obesity and diabetes, which partially result from the metabolic action of n-3 LC-PUFAs in adipose tissue. Recent studies highlight the importance of mitochondria in adipose tissue for the maintenance of systemic insulin sensitivity. For instance, both n-3 LC-PUFAs and the antidiabetic drugs TZDs (thiazolidinediones) induce mitochondrial biogenesis and beta-oxidation. The activation of this 'metabolic switch' in adipocytes leads to a decrease in adiposity. Both n-3 LC-PUFAs and TZDs ameliorate a low-grade inflammation of adipose tissue associated with obesity and induce changes in the pattern of secreted adipokines, resulting in improved systemic insulin sensitivity. In contrast with TZDs, which act as agonists of PPARgamma (peroxisome-proliferator-activated receptor-gamma) and promote differentiation of adipocytes and adipose tissue growth, n-3 LC-PUFAs affect fat cells by different mechanisms, including the transcription factors PPARalpha and PPARdelta. Some of the effects of n-3 LC-PUFAs on adipose tissue depend on their active metabolites, especially eicosanoids. Thus treatments affecting adipose tissue by multiple mechanisms, such as combining n-3 LC-PUFAs with either caloric restriction or antidiabetic/anti-obesity drugs, should be explored.

Effects of Eicosapentaenoic Acid Treatment on Epicardial and Abdominal Visceral Adipose Tissue Volumes in Patients with Coronary Artery Disease

“…As AA and EPA compete for cyclo-oxygenases (COXs), and both EPA and DHA directly inhibit COX activities, a relatively small increase in plasma n-3 PUFAs levels would significantly inhibit the synthesis of eicosanoids from AA 28) . n-3 PUFAs are a naturally occurring potent regulator of adiponectin secretion, and they exert insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects in vivo 29) .…”

n-3 PUFA: bioavailability and modulation of adipose tissue function

“…Part of the metabolic effects of n-3 LC PUFA in the liver (36) , and possibly also in other tissues (24,37) (also, see later), is mediated by the stimulation of AMP-activated protein kinase (AMPK), a metabolic sensor controlling intracellular metabolic fluxes, i.e. the partitioning between lipid oxidation and lipogenesis (for review, see Flachs et al (23) and Carling (38) ). Thus, n-3 LC PUFA by multiple mechanisms of action modulate the functions of all major tissues involved in the development of MS, i.e.…”

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

“…The important role of WAT in energy homeostasis is underscored by the findings that WAT is one of the key organs affected by calorie restriction, the most effective strategy to prolong a healthy life in several species [3], and by the fact that accumulation of body fat can be reduced through upregulation of lipid catabolism in WAT [4][5][6][7][8][9][10]. The metabolism and secretory functions of WAT are also modulated by longchain (LC) n-3 polyunsaturated fatty acids (PUFA), namely eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3), which exert numerous beneficial effects on health, including improvements in lipid metabolism and prevention of obesity and diabetes [11], while decreasing the rate of fatal coronary heart disease in diabetic patients who have had a myocardial infarction [12]. The metabolic changes induced by both calorie restriction and LC n-3 PUFA include induction of mitochondrial biogenesis and lipid catabolism in WAT [3,13].…”