ArrayExpress Uploader0mousenot specifiedC57BL/6not specifiedregular dietWTnot specifiedC57BL/6not specifiedregular dietWTnot specifiedC57BL/6not specifiedhigh fat dietWTnot specifiedC57BL/6not specifiedhigh fat dietWTnot specifiedmixed strains of C57BL/6 and NIH Black Swiss females (Taconic)not specifiedregular dietSmad3-/-not specifiedmixed strains of C57BL/6 and NIH Black Swiss females (Taconic)not specifiedregular dietSmad3-/-not specifiedmixed strains of C57BL/6 and NIH Black Swiss females (Taconic)not specifiedhigh fat dietSmad3-/-not specifiedmixed strains of C57BL/6 and NIH Black Swiss females (Taconic)not specifiedhigh fat dietSmad3-/-13C4C57J/B6IgGdiet induced obesenot specified13C4C57J/B6IgGdiet induced obesenot specified1D11C57J/B6TGF-betadiet induced obesenot specified1D11C57J/B6TGF-betadiet induced obesenot specified6444arrayexpress_sid6Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an...21723505E-GEOD-28598/profile/8773/arrayexpressuploader512adipose tissuebasalglucosemuscleobesitywhite adipose tissueDec.12, 2014FalseE-GEOD-28598_A-AFFY-45protection-from-obesity-and-diabetes-by-blockade-oProtection from obesity and diabetes by blockade of TGF-beta/Smad3 signalingNov.11, 2014Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an important role of the TGF-beta/Smad3 signaling pathway in regulating glucose and energy homeostasis. Smad3 deficient mice are protected from diet-induced obesity and diabetes. Interestingly, the metabolic protection is accompanied by Smad3-/- white adipose tissue acquiring the bioenergetic and gene expression profile of brown fat/skeletal muscle. Smad3-/- adipocytes demonstrate a marked increase in mitochondrial biogenesis, with a corresponding increase in basal respiration, and Smad3 acts as a repressor of PGC-alpha1 expression. We observe significant correlation between TGF-beta1 levels and adiposity in rodents and humans. Further, systemic blockade of TGF-beta1 signaling protects mice from obesity, diabetes and hepatic steatosis. Together, these results demonstrate that TGF-beta signaling regulates glucose tolerance and energy homeostasis and suggest that modulation of TGF-beta1 activity might be an effective treatment strategy for obesity and diabetes. Smad3-/- and WT mice were fed with regular diet (RD) and high fat diet (HFD), and diet induced obese (DIO) mice were treated with IgG and anti-TGF-b1 antibodyhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-28598http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-28598/samples/