Endocrine Abstracts

Omega-3 polyunsaturated fatty acids modulate the risk factors for metabolic syndrome via multiple mechanisms. However, their underlying mechanisms on insulin resistance and type 2 diabetes are still unknown. Here, we report that Odontella aurita, a microalga rich in the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), prevents high saturated fat diet induced insulin resistance and inflammation in the liver of Wistar rats. High fat diet (HFD), given for 8 weeks, increased plasma insulin levels associated with the down-regulation of insulin receptor (IR) and the impairment of insulin-dependent IR phosphorylation. Furthermore, HFD increased toll-like receptor 4 (TLR4) expressions. Indeed, we have recently reported that TLR4 is implicated in resistin-induced inflammation and insulin resistance in the hypothalamus.¹ We also show that TLR-4 up-regulation is concomitant with the activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). Importantly, Odontella aurita enriched HFD (HFOA, 12%) normalized body weight and plasma insulin levels, and restores IR expression at both protein and mRNA levels. In addition, HFAO improves insulin responsiveness as estimated by in vitro phosphorylation of hepatic plasma membrane IR. Furthermore, HFOA decreased TLR4 expression and JNK/p38 phosphorylation. In conclusion, we demonstrate, for the first time to our knowledge, that omega-3 fatty acids brought by Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways.

Disclosure: This work was supported by funds from University of Paris Sud and the CNRS (centre nationale de la recherche scientifique, France).

Reference: 1. Benomar Y, Gertler A, De Lacy P, Crépin D, Ould Hamouda H, Riffault L & Taouis M. Central resistin overexposure induces insulin resistance through Toll-like receptor 4. Diabetes 2013 62 102–114.