title: Crif1 deficiency reduces adipose OXPHOS capacity and triggers inflammation and insulin resistance in mice.
abstract: Impaired mitochondrial oxidative phosphorylation (OXPHOS) has been proposed as an etiological mechanism underlying insulin resistance. However, the initiating organ of OXPHOS dysfunction during the development of systemic insulin resistance has yet to be identified. To determine whether adipose OXPHOS deficiency plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with OXPHOS-deficient adipose tissue was examined. Crif1 is a protein required for the intramitochondrial production of mtDNA-encoded OXPHOS subunits; therefore, Crif1 haploinsufficient deficiency in mice results in a mild, but specific, failure of OXPHOS capacity in vivo. Although adipose-specific Crif1-haploinsufficient mice showed normal growth and development, they became insulin-resistant. Crif1-silenced adipocytes showed higher expression of chemokines, the expression of which is dependent upon stress kinases and antioxidant. Accordingly, examination of adipose tissue from Crif1-haploinsufficient mice revealed increased secretion of MCP1 and TNFα, as well as marked infiltration by macrophages. These findings indicate that the OXPHOS status of adipose tissue determines its metabolic and inflammatory responses, and may cause systemic inflammation and insulin resistance.
authors.affiliation: Research Center for Endocrine and Metabolic Diseases, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Ryu
authors.forename: Soung Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yong Kyung
authors.initials: YK
authors.lastname: Kim
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Choi
authors.forename: Surendar
authors.initials: S
authors.lastname: Tadi
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Seong Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Hyo Kyun
authors.initials: HK
authors.lastname: Chung
authors.forename: Saet Byel
authors.initials: SB
authors.lastname: Jung
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jo
authors.forename: Koon Soon
authors.initials: KS
authors.lastname: Kim
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Gi Ryang
authors.initials: GR
authors.lastname: Kweon
authors.forename: Ki Cheol
authors.initials: KC
authors.lastname: Park
authors.forename: Jung Uee
authors.initials: JU
authors.lastname: Lee
authors.forename: Young Yun
authors.initials: YY
authors.lastname: Kong
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Jongkyeong
authors.initials: J
authors.lastname: Chung
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D057895:Haploinsufficiency; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation
chemical_list: D018797:Cell Cycle Proteins; C527307:Crif1 protein, mouse; D004272:DNA, Mitochondrial; D007328:Insulin