Lipolysis is altered in MHC class I zinc-alpha(2)-glycoprotein deficient mice.
Non-conventional major histocompatibility complex class I molecules are involved in a variety of physiological functions, most at the periphery of the immune system per se. Zinc-alpha(2)-glycoprotein (ZAG), the sole soluble member of this superfamily has been implicated in cachexia, a poorly understood yet life-threatening, severe wasting syndrome. To further ascertain the role of ZAG in lipid metabolism and perhaps the immune system, we inactivated both ZAG alleles by gene targeting in mice. Subjecting these ZAG deficient animals to standard or lipid rich food regimens led to increased body weight in comparison to identically treated wild-type mice. This phenotype appeared to correlate with a significant decrease in adipocytic lipolysis that could not be rescued by several pharmacological agents including beta(3)-adrenoreceptor agonists. Furthermore, in contrast to previously reported data, ZAG was found to be ubiquitously and constitutively expressed, with an especially high level in the mouse liver. No overt immunological phenotype was identified in these animals.
Rolli
Véronique
V
Immunogénétique Moléculaire Humaine, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Hôpitaux Universitaires de Strasbourg, 4 Rue Kirschleger, 67085 Strasbourg Cedex, France.
Radosavljevic
Mirjana
M
Astier
Valérie
V
Macquin
Cécile
C
Castan-Laurell
Isabelle
I
Visentin
Virgile
V
Guigné
Charlotte
C
Carpéné
Christian
C
Valet
Philippe
P
Gilfillan
Susan
S
Bahram
Seiamak
S
D017667:Adipocytes / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D015870:Gene Expression; D018390:Gene Targeting; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008066:Lipolysis / Q000502:physiology*; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014162:Transfection; D015430:Weight Gain; D000090203:Zn-Alpha-2-Glycoprotein
D058667:Adrenergic beta-3 Receptor Agonists; D004041:Dietary Fats; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D011994:Recombinant Proteins; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein; D004247:DNA