Reduced adiponectin expression after high-fat diet is associated with selective up-regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue

Abstract

Adiponectin is an adipocyte-derived adipokine with potent antidiabetic, anti-inflammatory, and antiatherogenic activity. Long-term, high-fat diet results in gain of bodyweight, adiposity, further inflammatory-based cardiovascular diseases, and reduced adiponectin secretion. VitaminAderivatives/retinoids are involved in several of these processes,which mainly take place inwhite adipose tissue (WAT). In this study,we examined adiponectin expression as a function of dietary high-fat and high-Vitamin A conditions in mice. A decrease of adiponectin expression in addition to an up-regulation of aldehyde dehydrogenase A1 (ALDH1A1), retinoid signaling, and retinoic acid response element signaling was selectively observed inWAT of mice fed a normal-vitaminA, high-fat diet. Reduced adiponectin expression inWATwas also observed inmice fed a high-Vitamin A diet. Adipocyte cell culture revealed that endogenous and synthetic retinoic acid receptor (RAR)a- andRARg-selective agonists, aswell as a synthetic retinoidXreceptor agonist, efficiently reducedadiponectinexpression,whereasALDH1A1 expression only increased with RAR agonists. We conclude that reduced adiponectin expression under high-fat dietary conditions is dependent on 1) increased ALDH1A1 expression in adipocytes,which does not increase all-trans-retinoic acid levels; 2) further RAR ligand-induced, WAT-selective, increased retinoic acid response element-mediated signaling; and 3) RARligand-dependent reduction of adiponectin expression.-Landrier, J.-F., Kasiri, E., Karkeni, E., Mihaly, J., Beke, G.,Weiss, K., Lucas, R., Aydemir, G., Salles, J., Walrand, S., de Lera, A. R., Ruhl, R. Reduced adiponectin expression after high-fat diet is associated with selective up-regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue. FASEB J. 31, 203-211 (2017). www.fasebj.org.