Park 2018 J Clin Invest
| Park H, He A, Tan M, Johnson JM, Dean JM, Pietka TA, Chen Y, Zhang X, Hsu FF, Razani B, Funai K, Lodhi IJ (2018) Peroxisome-derived lipids regulate adipose thermogenesis by mediating cold-induced mitochondrial fission. J Clin Invest 129:694-711. |
Park H, He A, Tan M, Johnson JM, Dean JM, Pietka TA, Chen Yali, Zhang Xiangyu, Hsu FF, Razani B, Funai Katsuhiko, Lodhi IJ (2018) J Clin Invest
Abstract: Peroxisomes perform essential functions in lipid metabolism, including fatty acid oxidation and plasmalogen synthesis. Here, we describe a role for peroxisomal lipid metabolism in mitochondrial dynamics in brown and beige adipocytes. Adipose tissue peroxisomal biogenesis was induced in response to cold exposure through activation of the thermogenic co-regulator PRDM16. Adipose-specific knockout of the peroxisomal biogenesis factor Pex16 (Pex16-AKO) in mice impaired cold tolerance, decreased energy expenditure, and increased diet-induced obesity. Pex16 deficiency blocked cold-induced mitochondrial fission, decreased mitochondrial copy number, and caused mitochondrial dysfunction. Adipose-specific knockout of the peroxisomal beta-oxidation enzyme acyl CoA oxidase 1 (Acox1-AKO) was not sufficient to affect adiposity, thermogenesis or mitochondrial copy number, but knockdown of the plasmalogen synthetic enzyme glyceronephosphate O-acyltransferase (GNPAT) recapitulated the effects of Pex16 inactivation on mitochondrial morphology and function. Plasmalogens are present in mitochondria and decreased with Pex16 inactivation. Their dietary supplementation increased mitochondrial copy number, improved mitochondrial function, and rescued thermogenesis in Pex16-AKO mice. These findings support a surprising interaction between peroxisomes and mitochondria to regulate mitochondrial dynamics and thermogenesis. • Keywords: Adipose tissue, Cell Biology, Metabolism, Mitochondria • Bioblast editor: Plangger M • O2k-Network Lab: US MO St Louis Abumrad NA, US UT Salt Lake City Funai K
Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression
Organism: Mouse
Tissue;cell: Fat
Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET
Pathway: F, N, S
HRR: Oxygraph-2k
2018-12, US
