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- W4319334018 abstract "Healthy expansion of adipose tissue is critical for the maintenance of metabolic health, providing an optimized reservoir for energy storage in the form of triacylglycerol-rich lipoproteins. Dysfunctional adipocytes that are unable to efficiently store lipid can result in lipodystrophy and contribute to nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. Leucine-rich repeat containing protein 8a/SWELL1 functionally encodes the volume-regulated anion channel complex in adipocytes, is induced in early obesity, and is required for normal adipocyte expansion during high-fat feeding. Adipose-specific SWELL1 ablation (Adipo KO) leads to insulin resistance and hyperglycemia during caloric excess, both of which are associated with NAFLD. Here, we show that Adipo-KO mice exhibited impaired adipose depot expansion and excess lipolysis when raised on a variety of high-fat diets, resulting in increased diacylglycerides and hepatic steatosis, thereby driving liver injury. Liver lipidomic analysis revealed increases in oleic acid-containing hepatic triacylglycerides and injurious hepatic diacylglyceride species, with reductions in hepatocyte-protective phospholipids and antiinflammatory free fatty acids. Aged Adipo-KO mice developed hepatic steatosis on a regular chow diet, and Adipo-KO male mice developed spontaneous, aggressive hepatocellular carcinomas (HCCs). These data highlight the importance of adipocyte SWELL1 for healthy adipocyte expansion to protect against NAFLD and HCC in the setting of overnutrition and with aging." @default.
- W4319334018 created "2023-02-08" @default.
- W4319334018 creator A5034317745 @default.
- W4319334018 creator A5035590977 @default.
- W4319334018 creator A5048457080 @default.
- W4319334018 creator A5050987528 @default.
- W4319334018 creator A5064451801 @default.
- W4319334018 creator A5072812232 @default.
- W4319334018 creator A5081714923 @default.
- W4319334018 creator A5084791102 @default.
- W4319334018 date "2023-03-08" @default.
- W4319334018 modified "2023-09-26" @default.
- W4319334018 title "Adipose-targeted SWELL1 deletion exacerbates obesity- and age-related nonalcoholic fatty liver disease" @default.
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- W4319334018 doi "https://doi.org/10.1172/jci.insight.154940" @default.