GDF-3 is an adipogenic cytokine under high fat dietary condition.
Growth differentiation factor 3 (GDF-3) is structurally a bone morphogenetic protein/growth differentiation factor subfamily member of the TGF-beta superfamily. GDF-3 exhibits highest level of expression in white fat tissue in mice and is greatly induced by high fat diet if fat metabolic pathway is blocked. To identify its biological function, GDF-3 was overexpressed in mice by adenovirus mediated gene transfer. Mice transduced with GDF-3 displayed profound weight gain when fed with high fat diet. The phenotypes included greatly expanded adipose tissue mass, increased body adiposity, highly hypertrophic adipocytes, hepatic steatosis, and elevated plasma leptin. GDF-3 stimulated peroxisome proliferator activated receptor expression in adipocytes, a master nuclear receptor that controls adipogenesis. However, GDF-3 was not involved in blood glucose homeostasis or insulin resistance, a condition associated with obesity. In contrast, similar phenotypes were not observed in GDF-3 mice fed with normal chow, indicating that GDF-3 is only active under high lipid load. Thus, GDF-3 is a new non-diabetic adipogenic factor tightly coupled with fat metabolism.
Wang
Wei
W
Human Genome Sciences, Inc., 9410 Key West Avenue, Rockville, MD 20850, USA.
Yang
Yan
Y
Meng
Ying
Y
Shi
Yanggu
Y
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000273:Adipose Tissue / Q000254:growth & development*; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D048429:Cell Size / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage*; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D055451:Growth Differentiation Factor 3; D006801:Humans; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014161:Transduction, Genetic; D015430:Weight Gain / Q000235:genetics / Q000502:physiology
D001786:Blood Glucose; D016207:Cytokines; D004041:Dietary Fats; C525974:GDF3 protein, human; C525975:Gdf3 protein, mouse; D055451:Growth Differentiation Factor 3; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D004247:DNA