Regulator of G protein signaling-4 controls fatty acid and glucose homeostasis.

Irena Iankova (1, 2) , Carine Chavey (1, 2) , Cyrielle Clapé (1, 2) , Claude Colomer (3) , Nathalie C. Guérineau (3) , Nicolas Grillet (4, 5) , Jean-François Brunet (4) , Jean-Sébastien Annicotte (1, 2) , Lluis Fajas (1, 2, 6)

1 Métabolisme et cancer
2 IRCM - U896 Inserm - UM1 - Institut de recherche en cancérologie de Montpellier
3 IGF - Institut de Génomique Fonctionnelle
4 DESN - Développement et évolution du système nerveux
5 The Scripps Research Institute [La Jolla, San Diego]
6 Hôpital Arnaud de Villeneuve [CHRU Montpellier]

Circulating free fatty acids are a reflection of the balance between lipogenesis and lipolysis that takes place mainly in adipose tissue. We found that mice deficient for regulator of G protein signaling (RGS)-4 have increased circulating catecholamines, and increased free fatty acids. Consequently, RGS4-/- mice have increased concentration of circulating free fatty acids; abnormally accumulate fatty acids in liver, resulting in liver steatosis; and show a higher degree of glucose intolerance and decreased insulin secretion in pancreas. We show in this study that RGS4 controls adipose tissue lipolysis through regulation of the secretion of catecholamines by adrenal glands. RGS4 controls the balance between adipose tissue lipolysis and lipogenesis, secondary to its role in the regulation of catecholamine secretion by adrenal glands. RGS4 therefore could be a good target for the treatment of metabolic diseases.

Mots clés: RGS4; lipolysis; catecholamines; liver steatosis; insulin secretion

Domaines: Endocrinologie et métabolisme

Irena Iankova, Carine Chavey, Cyrielle Clapé, Claude Colomer, Nathalie C. Guérineau, et al.. Regulator of G protein signaling-4 controls fatty acid and glucose homeostasis.. Endocrinology, 2008, 149 (11), pp.5706-12. ⟨10.1210/en.2008-0717⟩. ⟨inserm-00310771⟩