Abstract | OBJECTIVE: METHODS: Wild-type and Siah2KO mice were fed a low- or high-fat diet for 16 weeks. Indirect calorimetry, body composition, and glucose and insulin tolerance were assayed along with glucose and insulin levels. Gene and protein expression, immunohistochemistry, adipocyte size distribution, and lipolysis were also analyzed. RESULTS: Enlarged adipocytes in obese Siah2KO mice were not associated with obesity-induced insulin resistance. Proinflammatory gene expression, stress kinase signaling, fibrosis, and crown-like structures were reduced in the Siah2KO adipose tissue, and Siah2KO adipocytes were more responsive to insulin-dependent inhibition of lipolysis. Loss of Siah2 increased expression of PPARγ target genes involved in lipid metabolism and decreased expression of proinflammatory adipokines regulated by PPARγ. CONCLUSIONS: Siah2 links adipocyte hypertrophy with adipocyte dysfunction and recruitment of proinflammatory immune cells to adipose tissue. Selective regulation of PPARγ activity is a Siah2-mediated mechanism contributing to obesity-induced adipose tissue inflammation.
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Authors | Gail Kilroy, Lauren E Carter, Susan Newman, David H Burk, Justin Manuel, Andreas Möller, David D Bowtell, Randall L Mynatt, Sujoy Ghosh, Z Elizabeth Floyd |
Journal | Obesity (Silver Spring, Md.)
(Obesity (Silver Spring))
Vol. 23
Issue 11
Pg. 2223-32
(Nov 2015)
ISSN: 1930-739X [Electronic] United States |
PMID | 26380945
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2015 The Obesity Society. |
Chemical References |
- Ubiquitin
- Siah2 protein, mouse
- Ubiquitin-Protein Ligases
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Topics |
- Adipocytes
(metabolism, pathology)
- Adipose Tissue
(metabolism, pathology)
- Animals
- Diet, High-Fat
- Hypertrophy
(genetics)
- Inflammation
(genetics, metabolism)
- Insulin Resistance
(genetics)
- Lipolysis
(genetics)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Obese
- Obesity
(complications, genetics, metabolism)
- Panniculitis
(genetics, metabolism, pathology)
- Ubiquitin
- Ubiquitin-Protein Ligases
(genetics, physiology)
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