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- W2896064918 abstract "Nonalcoholic fatty liver disease (NAFLD) arises from mitochondrial dysfunction under sustained imbalance between energy intake and expenditure, but the underlying mechanisms controlling mitochondrial respiration have not been entirely understood. Heterotrimeric G proteins converge with activated GPCRs to modulate cell-signaling pathways to maintain metabolic homeostasis. Here, we investigated the regulatory role of G protein α12 (Gα12) on hepatic lipid metabolism and whole-body energy expenditure in mice. Fasting increased Gα12 levels in mouse liver. Gα12 ablation markedly augmented fasting-induced hepatic fat accumulation. cDNA microarray analysis from Gna12-KO liver revealed that the Gα12-signaling pathway regulated sirtuin 1 (SIRT1) and PPARα, which are responsible for mitochondrial respiration. Defective induction of SIRT1 upon fasting was observed in the liver of Gna12-KO mice, which was reversed by lentivirus-mediated Gα12 overexpression in hepatocytes. Mechanistically, Gα12 stabilized SIRT1 protein through transcriptional induction of ubiquitin-specific peptidase 22 (USP22) via HIF-1α increase. Gα12 levels were markedly diminished in liver biopsies from NAFLD patients. Consistently, Gna12-KO mice fed a high-fat diet displayed greater susceptibility to diet-induced liver steatosis and obesity due to decrease in energy expenditure. Our results demonstrate that Gα12 regulates SIRT1-dependent mitochondrial respiration through HIF-1α-dependent USP22 induction, identifying Gα12 as an upstream molecule that contributes to the regulation of mitochondrial energy expenditure." @default.
- W2896064918 created "2018-10-26" @default.
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- W2896064918 date "2018-11-12" @default.
- W2896064918 modified "2023-10-16" @default.
- W2896064918 title "Gα12 ablation exacerbates liver steatosis and obesity by suppressing USP22/SIRT1-regulated mitochondrial respiration" @default.
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- W2896064918 cites W1972148870 @default.
- W2896064918 cites W1972501434 @default.
- W2896064918 cites W1972709924 @default.
- W2896064918 cites W1975391500 @default.
- W2896064918 cites W1975452261 @default.
- W2896064918 cites W1975962309 @default.
- W2896064918 cites W1983550104 @default.
- W2896064918 cites W1985592156 @default.
- W2896064918 cites W1988848092 @default.
- W2896064918 cites W1993324234 @default.
- W2896064918 cites W1993397999 @default.
- W2896064918 cites W1996094302 @default.
- W2896064918 cites W1996821192 @default.
- W2896064918 cites W1998334660 @default.
- W2896064918 cites W1998647619 @default.
- W2896064918 cites W2001428385 @default.
- W2896064918 cites W2003483275 @default.
- W2896064918 cites W2005348378 @default.
- W2896064918 cites W2016057875 @default.
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- W2896064918 cites W2035123506 @default.
- W2896064918 cites W2038018821 @default.
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- W2896064918 cites W2047454594 @default.
- W2896064918 cites W2050175789 @default.
- W2896064918 cites W2055900062 @default.
- W2896064918 cites W2056913859 @default.
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- W2896064918 cites W2129163454 @default.
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- W2896064918 doi "https://doi.org/10.1172/jci97831" @default.
- W2896064918 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6264648" @default.
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