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

Abstract

Adipose tissue has a key role in the development of metabolic syndrome (MS), which includes obesity, type 2 diabetes, dyslipidaemia, hypertension and other disorders. Systemic insulin resistance represents a major factor contributing to the development of MS in obesity. The resistance is precipitated by impaired adipose tissue glucose and lipid metabolism, linked to a low-grade inflammation of adipose tissue and secretion of pro-inflammatory adipokines. Development of MS could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the successful therapy of MS. The n-3 long-chain (LC) PUFA, EPA and DHA, which are abundant in marine fish, act as hypolipidaemic factors, reduce cardiac events and decrease the progression of atherosclerosis. Thus, n-3 LC PUFA represent healthy constituents of diets for patients with MS. In rodents n-3 LC PUFA prevent the development of obesity and impaired glucose tolerance. The effects of n-3 LC PUFA are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms. n-3 LC PUFA activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation of n-3 LC PUFA in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects of n-3 LC PUFA, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation by n-3 LC PUFA.

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

“…We have demonstrated previously that AMP-activated protein kinase (AMPK), a cellular energy sensor, is involved in the effects of LC n-3 PUFA on hepatic lipid and glucose metabolism [30] and that it is activated in WAT by LC n-3 PUFA [47]. AMPK activation in adipocytes results in increased mitochondrial biogenesis and lipid catabolism [4,48].…”

Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase

“…Importantly, lipid catabolism in WAT was always up-regulated, and in situ lipogenesis in WAT was suppressed (Orci et al 2004;Ribet et al 2010;Flachs et al 2005;Tiraby et al 2003;Wilson-Fritch et al 2004), suggesting activation of AMPK Genes Nutr (2012) 7:369-386 381 in response to decreased energy status in WAT. Indeed, when studied under the conditions of the above treatments, AMPK in WAT and other tissues was found to be activated (Jelenik et al 2010;Kopecky et al 2009;Orci et al 2004;Ye et al 2006). Concerning the mechanism of energy expenditure induced by the treatments, mitochondrial uncoupling mediated by UCP1 in WAT adipocytes (Orci et al 2004;Tiraby et al 2003;Petrovic et al 2010;Collins et al 1997;Guerra et al 1998;Himms-Hagen et al 2000) could be involved in most of the cases.…”

“…For example, leptin activates AMPK in adipose tissue, SM, and liver but inhibits it in hypothalamus (Lim et al 2010), while adiponectin and anti-diabetic drugs primarily activate the AMPK in the peripheral tissues. Furthermore, there is a number of natural food components believed to exert beneficial effects on health in association with activation of AMPK like plant polyphenols (Um et al 2010) or n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) (Jelenik et al 2010;Kopecky et al 2009). The role of AMPK in energy metabolism has been most intensively studied in SM, heart, adipose tissue, liver, beta cells, and hypothalamus, that is, tissues that are highly sensitive to changes in energy balance and also actively involved in its regulation.…”

“…Furthermore, the adipokines leptin and adiponectin (Orci et al 2004;Wu et al 2003) and dietary n-3 PUFA (Kopecky et al 2009) activate AMPK in WAT. It has been found in rodent adipocytes that lipolytic and cAMP-elevating stimuli increase AMPK activity, while its activation by AICAR or phenformin strongly reduces isoproterenol-induced lipolysis and fatty acid release (Daval et al 2005).…”

“…Concerning the induction of energy expenditure in WAT, several physiologically relevant treatments in mice have been demonstrated to induce a phenotype similar to that of aP2-Ucp1 mice for review). Thus, treatment using leptin (Orci et al 2004), PPARa agonists (Ribet et al 2010), adrenoreceptor agonists and lipolytic agents (Granneman et al 2003;Yehuda-Shnaidman et al 2010), dietary n-3 polyunsaturated fatty acids (Jelenik et al 2010;Kopecky et al 2009;Flachs et al 2005), and thiazolidinediones acting as specific agonists of PPARc [TZD; (Tiraby et al 2003;Wilson-Fritch et al 2004;Petrovic et al 2010)] resulted in reduced adiposity and metabolic disturbances related to obesity, observed mostly under the conditions of high-fat feeding in obesity-prone C57BL/6 mice. Importantly, lipid catabolism in WAT was always up-regulated, and in situ lipogenesis in WAT was suppressed (Orci et al 2004;Ribet et al 2010;Flachs et al 2005;Tiraby et al 2003;Wilson-Fritch et al 2004), suggesting activation of AMPK Genes Nutr (2012) 7:369-386 381 in response to decreased energy status in WAT.…”