Resistance to the Lipolytic Action of Epinephrine: A New Feature of Protein Gs Deficiency
Jean Claude Carel,
Catherine Le Stunff,
Luce Condamine,
Eric Mallet,
Jean Louis Chaussain,
Pierre Adnot,
Michèle Garabédian and
Pierre Bougnères
Department of Pediatric Endocrinology and INSERM U342 (J.C.C.,
C.L.S, L.C., J.L.C., P.B.), and CNRS UPR 1524 (L.C., M.G.),
Hôpital Saint Vincent de Paul, 75014 Paris, France; Department of
Pediatrics (E.M.), Hôpital Charles Nicolle, 76000 Rouen,
France; and Centre de Recherche (P.A.), Groupe LIPHA, 91380
Chilly-Mazarin, France
Address correspondence and requests for reprints to: Dr. Jean-Claude Carel, INSERM U342, Hôpital Saint Vincent de Paul 82 av Denfert Rochereau, 75014 Paris, France. E-mail:
carel{at}cochin.inserm.fr
Deficiency of protein Gs (Gs; OMIM no.103580), the
stimulatoryregulator of adenylyl cyclase, is associated with
resistanceto PTH and other hormones, sc calcifications, short stature,
andskeletal defects (Albright’s hereditary osteodystrophy).It is
caused by heterozygous loss of function mutations in GNAS1,the gene
encoding the -subunit of Gs. Obesity is a
classicalfeature of patients with Gs deficiency, but the
mechanism leadingto fat accumulation has not been elucidated. We
measured glycerolflux, using a nonradioactive tracer dilution
approach, to analyzethe lipolytic response to epinephrine in 6
patients with Gsdeficiency and PTH resistance and compared
it to six age-matchednormal controls and nine massively obese
children. Basal glycerolproduction was reduced by 50%, and lipolytic
response to epinephrinewas reduced by 67%, in
Gs-deficient children, as compared withcontrols. The
degree of impairment of lipolysis was similarin
Gs-deficient children who were only moderately overweight
andin morbidly obese children. These findings extend the spectrumof
hormonal resistance in Gs deficiency. Besides
ß-adrenergicreceptors, Gs protein itself should be
examined as a possiblestep involved in the decreased lipolysis
observed in commonobesity.
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-subunit of Gs. Obesity is a
classical feature of patients with Gs deficiency, but the
mechanism leading to fat accumulation has not been elucidated. We
measured glycerol flux, using a nonradioactive tracer dilution
approach, to analyze the lipolytic response to epinephrine in 6
patients with Gs deficiency and PTH resistance and compared
it to six age-matched normal controls and nine massively obese
children. Basal glycerol production was reduced by 50%, and lipolytic
response to epinephrine was reduced by 67%, in
Gs-deficient children, as compared with controls. The
degree of impairment of lipolysis was similar in
Gs-deficient children who were only moderately overweight
and in morbidly obese children. These findings extend the spectrum of
hormonal resistance in Gs deficiency. Besides
ß-adrenergic receptors, Gs protein itself should be
examined as a possible step involved in the decreased lipolysis
observed in common obesity. 
