Defective stimulation of adipocyte adenylate cyclase, blunted lipolysis, and obesity in pseudohypoparathyroidism 1a.
Adipocyte plasma membranes were isolated from four patients with type 1a pseudohypoparathyroidism, a disease in which deficiency of the stimulatory guanine nucleotide binding protein Gs has been reported, and from controls. Stimulation of adenylate cyclase by isoproterenol was defective, whereas inhibition of forskolin-stimulated cyclase activity by N6-(phenylisopropyl)adenosine was normal. The patients had low serum FFA concentrations and developed obesity in childhood. These results suggest that pseudohypoparathyroidism 1a is connected with a blunted stimulatory response of adenylate cyclase, possibly because of low Gs activity, and that this blunted response may lead to decreased lipolysis and to obesity.
Kaartinen
J M
JM
Department of Medical Chemistry, University of Helsinki, Finland.
Käär
M L
ML
Ohisalo
J J
JJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D019204:GTP-Binding Proteins / Q000172:deficiency; D006801:Humans; D008066:Lipolysis; D008297:Male; D009765:Obesity / Q000209:etiology*; D010375:Pedigree; D011547:Pseudohypoparathyroidism / Q000150:complications* / Q000235:genetics / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases