Regulator of G protein signaling-4 controls fatty acid and glucose homeostasis.
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.
Iankova
Irena
I
Institut National de la Santé et de la Recherche Médicale, Unité 834, Montpellier F-34298, France.
Chavey
Carine
C
Clapé
Cyrielle
C
Colomer
Claude
C
Guérineau
Nathalie C
NC
Grillet
Nicolas
N
Brunet
Jean-François
JF
Annicotte
Jean-Sébastien
JS
Fajas
Lluis
L
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004036:Diet, Atherogenic; D005215:Fasting / Q000097:blood; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005234:Fatty Liver / Q000150:complications / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics*; D006943:Hyperglycemia / Q000150:complications / Q000235:genetics; D006946:Hyperinsulinism / Q000150:complications / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050155:Lipogenesis / Q000235:genetics; D008066:Lipolysis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*
D005227:Fatty Acids; D007328:Insulin; D020710:RGS Proteins; C098799:RGS4 protein; D005947:Glucose