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| Status |
Public on Jul 13, 2011 |
| Title |
Protection from obesity and diabetes by blockade of TGF-beta/Smad3 signaling |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Imbalances 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.
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| Overall design |
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 antibody
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| Contributor(s) |
Yadav H, Quijano C, Kamaraju AK, Gavrilova O, Malek R, Chen W, Zerfas P, Zhigang D, Wright EC, Steulten C, Sun P, Lonning S, Skarulis M, Sumner AE, Finke T, Rane SG |
| Citation(s) |
21723505 |
| Submission date |
Apr 13, 2011 |
| Last update date |
Feb 11, 2019 |
| Contact name |
WeiPing Chen |
| E-mail(s) |
weipingChen@niddk.nih.gov
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| Phone |
301-496-0175
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| Organization name |
NIDDK/NIH
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| Department |
GCL
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| Lab |
Genomics Core Lab
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| Street address |
Bldg 8, Room 1A11, NIDDK/NIH
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA139107 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE28598_RAW.tar |
211.6 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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