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 signalingwas selectively observed in WAT of mice fed a normal–vitaminA, high‐fat diet. Reduced adiponectin expression in WAT was also observed in mice fed a high–vitamin A diet. Adipocyte cell culture revealed that endogenous and synthetic retinoic acid receptor (RAR)α‐ and RAR γ‐selective agonists, as well as a synthetic retinoid X receptor agonist, efficiently reduced adiponectin expression, whereas ALDH1A1 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) RAR ligand–dependent reduction of adiponectin expression.—Landrier, J.‐F., Kasiri, E., Karkeni, E., Mihály, J., Béke, G., Weiss, K., Lucas, R., Aydemir, G., Salles, J., Walrand, S., de Lera, A. R., Rühl, 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