title: SUMO-1 regulates body weight and adipogenesis via PPARγ in male and female mice.
abstract: Properly functioning adipose tissue is essential for normal insulin sensitivity of the body. When mice are kept on high-fat diet (HFD), adipose tissue expands, adipocytes increase in size and number, and the mice become obese. Many of these changes are mediated by the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), the activity of which is regulated by multiple posttranslational modifications, including SUMOylation. To address the role of small ubiquitin-like modifier-1 (SUMO-1) in PPARγ function in vivo, particularly in fat cell biology, we subjected Sumo1-knockout mice to HFD. Sumo1-null mice gained less weight and had smaller and fewer adipocytes in their gonadal fat tissue on HFD, but their glucose tolerance was similar to that of wild-type littermates. Adipogenesis was impaired in Sumo1-null cells, and expression of PPARγ target genes was attenuated. In addition, both Sumo1-null cells and Sumo1-null mice responded less efficiently to rosiglitazone, a PPARγ agonist. These findings indicate that SUMO-1 is important also for transcriptional activation by the PPARγ signaling pathway and not only for trans-repressive functions of PPARγ as previously reported.
authors.affiliation: Institute of Biomedicine, Physiology, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Mikkonen
authors.forename: Johanna
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Olli A
authors.initials: OA
authors.lastname: Jänne
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000502:physiology*; D052436:Adipose Tissue, White / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000235:genetics*; D059305:Diet, High-Fat; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000819:agonists / Q000502:physiology*; D000077154:Rosiglitazone; D025842:SUMO-1 Protein / Q000235:genetics* / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D047495:PPAR gamma; D025842:SUMO-1 Protein; D045162:Thiazolidinediones; D000077154:Rosiglitazone