Xia 2024 Nat Metab

From Bioblast
Publications in the MiPMap
Xia W, Veeragandham P, Cao Y, Yayun Xu Y, Rhyne TE, Qian J, Hung C-W, Zhao P, Jones Y, Gao H, Liddle C, Yu RT, Downes M, Evans RM, RydΓ©n M, Wabitsch M, Wang Z, Hakozaki H, SchΓΆneberg J, Reilly SM, Huang J, Saltiel AR (2024) Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation. Nat Metab 6:273–89. https://doi.org/10.1038/s42255-024-00978-0

Β» PMID: 38286821 Open Access

Xia W, Veeragandham P, Cao Y, Yayun Xu Y, Rhyne TE, Qian J, Hung C-W, Zhao P, Jones Y, Gao H, Liddle C, Yu RT, Downes M, Evans RM, Ryden M, Wabitsch M, Wang Zichen, Hakozaki H, Schoeneberg J, Reilly SM, Huang Jianfeng, Saltiel AR (2024) Nat Metab

Abstract: Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.

β€’ Bioblast editor: Gnaiger E


Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression, Exercise physiology;nutrition;life style  Pathology: Obesity  Stress:Mitochondrial disease  Organism: Human, Mouse  Tissue;cell: Fat  Preparation: Isolated mitochondria, Intact cells 


Coupling state: LEAK, ROUTINE, ET  Pathway:


Etomoxir, BMI 

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