Marine omega-3 fatty acids prevent myocardial insulin resistance and metabolic remodeling as induced experimentally by high insulin exposure

Abstract

Franekova V, Angin Y, Hoebers NT, Coumans WA, Simons PJ, Glatz JF, Luiken JJ, Larsen TS. Marine omega-3 fatty acids prevent myocardial insulin resistance and metabolic remodeling as induced experimentally by high insulin exposure. Am J Physiol Cell Physiol 308: C297-C307, 2015. First published December 4, 2014 doi:10.1152/ajpcell.00073.2014.-Insulin resistance is an important risk factor for the development of several cardiac pathologies, thus advocating strategies for restoring insulin sensitivity of the heart in these conditions. Omega-3 polyunsaturated fatty acids (-3 PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), have been shown to improve insulin sensitivity in insulin-sensitive tissues, but their direct effect on insulin signaling and metabolic parameters in the myocardium has not been reported previously. The aim of this study was therefore to examine the ability of EPA and DHA to prevent insulin resistance in isolated rat cardiomyocytes. Primary rat cardiomyocytes were made insulin resistant by 48 h incubation in high insulin (HI) medium. Parallel incubations were supplemented by 200 M EPA or DHA. Addition of EPA or DHA to the medium prevented the induction of insulin resistance in cardiomyocytes by preserving the phosphorylation state of key proteins in the insulin signaling cascade and by preventing persistent relocation of fatty acid transporter CD36 to the sarcolemma. Only cardiomyocytes incubated in the presence of EPA, however, exhibited improvements in glucose and fatty acid uptake and cell shortening. We conclude that -3 PUFAs protect metabolic and functional properties of cardiomyocytes subjected to insulin resistance-evoking conditions. omega-3 PUFAs; cardiac metabolism; insulin resistance; CD36; adipose triglyceride lipase; sarcomere shortening AN ELEVATED SUPPLY of lipids in obesity and type 2 diabetes leads to alterations of myocardial substrate metabolism, manifested insulin resistance with reduced glucose utilization, and increased long-chain fatty acid (LCFA) utilization (2, 3, 39). Thus isolated cardiomyocytes from various diabetic/obese rodent models show impaired insulin signaling, including reduced activation of protein kinase B (Akt/PKB), reduced glucose transporter 4 (GLUT4) translocation from intracellular compartments to the sarcolemma, as well as impaired insulininduced glucose uptake (10,35,37). Glucose and LCFA are the major substrates for the heart, and GLUT4 and CD36 the major substrate transporters, which are regulated by reversible insulin-induced translocation (48). Notably, increased LCFA supply to cardiomyocytes will evoke persistent relocation of CD36 from intracellular stores to the sarcolemma, followed by chronically elevated LCFA uptake and lipid accumulation, eventually resulting in insulin resistance (5, 36). Additionally, sustained hyperinsulinemia itself has also been shown to chronically stimulate CD36 translocation in cardiomyocytes and, consequently, lead to insulin resistance in a very similar manner to cardiom...

Serum fatty acid profile in psoriasis and its comorbidity

“…Furthermore, higher n-6/n-3 PUFAs ratio and low serum concentration of EPA and DHA in severe psoriasis, confirmed in our group of patients, may play important role in the development of comorbidity. Several studies in rat and mouse models of induced heart failure have reported that intake of EPA and DHA prevent left ventricular remodeling and contractile dysfunction [14]. Energy-restricted diet enriched in n-3 PUFA has protective effect on metabolic markers and clinical outcome in psoriatic patient with obesity [19].…”

Mechanisms Involved in the Improvement of Lipotoxicity and Impaired Lipid Metabolism by Dietary α-Linolenic Acid Rich Salvia hispanica L (Salba) Seed in the Heart of Dyslipemic Insulin-Resistant Rats

“…As in the CD-fed group, the hormone significantly induced the translocation of FAT/CD36 to the plasma membrane. Recently, in isolated rat cardiomyocytes incubated under insulin resistance evoking conditions, Franekova et al [ 41 ] demonstrated that the inclusion of EPA and DHA to the medium prevented the persistent translocation of CD36 to the sarcolemma and protected the metabolic and functional properties of the cardiomyocytes. In this regard, we previously demonstrated that the administration of dietary fish oil to SRD-fed rats was able to reverse heart muscle lipotoxicity and benefit key enzyme activities involved in the glucose metabolism [ 16 ].…”

CD36 actions in the heart: Lipids, calcium, inflammation, repair and more?

“…Interestingly, the evidence points to association of the early CD36 dysfunction observed with high fat feeding with an increase of postabsorptive insulin levels [60, 61]. Treatment of isolated rat cardiomyocytes with high insulin for 48h results in insulin resistance with persistent relocation of CD36 to the plasma membrane while inclusion of omega-3 polyunsaturated FA in the medium prevents this relocation and the onset of insulin resistance [62]. Posttranslational regulation of CD36 includes its ubiquitination, with opposite effects of FA and insulin [63], its glycosylation which was found altered in the heart of the spontaneously hypertensive rat [64] as well as its acetylation, palmitoylation, etc [3].…”