title: PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism.
abstract: Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2(-/-) Lep(ob)/Lep(ob) (POKO mouse), resulted in decreased fat mass, severe insulin resistance, beta-cell failure, and dyslipidaemia. Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species. Our data also indicate that PPARg2 may be required for the beta-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a) promoting adipose tissue expansion, (b) increasing the lipid-buffering capacity of peripheral organs, and (c) facilitating the adaptive proliferative response of beta-cells to insulin resistance.
authors.affiliation: Department of Clinical Biochemistry, Histopathology, University of Cambridge/Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Gema
authors.initials: G
authors.lastname: Medina-Gomez
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gray
authors.forename: Laxman
authors.initials: L
authors.lastname: Yetukuri
authors.forename: Kenju
authors.initials: K
authors.lastname: Shimomura
authors.forename: Sam
authors.initials: S
authors.lastname: Virtue
authors.forename: Mark
authors.initials: M
authors.lastname: Campbell
authors.forename: R Keira
authors.initials: RK
authors.lastname: Curtis
authors.forename: Mercedes
authors.initials: M
authors.lastname: Jimenez-Linan
authors.forename: Margaret
authors.initials: M
authors.lastname: Blount
authors.forename: Giles S H
authors.initials: GS
authors.lastname: Yeo
authors.forename: Miguel
authors.initials: M
authors.lastname: Lopez
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Seppänen-Laakso
authors.forename: Frances M
authors.initials: FM
authors.lastname: Ashcroft
authors.forename: Matej
authors.initials: M
authors.lastname: Oresic
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
mesh_terms: D000273:Adipose Tissue / Q000254:growth & development*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006943:Hyperglycemia / Q000235:genetics / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000009:adverse effects* / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D008954:Models, Biological; D047495:PPAR gamma / Q000235:genetics / Q000502:physiology*
chemical_list: D007328:Insulin; D008055:Lipids; D047495:PPAR gamma