title: The ubiquitin ligase Siah2 regulates obesity-induced adipose tissue inflammation.
abstract: OBJECTIVE
  Chronic, low-grade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Although ubiquitin ligases regulate inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored. Herein, the effect of the ubiquitin ligase Siah2 on obesity-related adipose tissue inflammation was examined.
  
  
  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.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Gail
authors.initials: G
authors.lastname: Kilroy
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Carter
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Newman
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Burk
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Manuel
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Möller
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: David D
authors.initials: DD
authors.lastname: Bowtell
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Randall L
authors.initials: RL
authors.lastname: Mynatt
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.|Cardiovascular and Metabolic Disease Program and Center for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Z Elizabeth
authors.initials: ZE
authors.lastname: Floyd
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D059305:Diet, High-Fat; D006984:Hypertrophy / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D008066:Lipolysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D015434:Panniculitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
chemical_list: D025801:Ubiquitin; C533102:Siah2 protein, mouse; D044767:Ubiquitin-Protein Ligases