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Article

Integrated Action of Autophagy and Adipose Tissue Triglyceride Lipase Ameliorates Diet-Induced Hepatic Steatosis in Liver-Specific PLIN2 Knockout Mice

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Obesity and Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
2
Laboratory for Nutrition and Vision Research, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
3
School of Health Sciences, Universidad CEU Cardenal Herrera, 46001 Valencia, Spain
4
Laboratory for Nutrition and Cancer Biology, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Ali Canbay and Lydie Combaret
Cells 2021, 10(5), 1016; https://doi.org/10.3390/cells10051016
Received: 16 March 2021 / Revised: 19 April 2021 / Accepted: 22 April 2021 / Published: 25 April 2021
An imbalance in the storage and breakdown of hepatic lipid droplet (LD) triglyceride (TAG) leads to hepatic steatosis, a defining feature of non-alcoholic fatty liver disease (NAFLD). The two primary cellular pathways regulating hepatic TAG catabolism are lipolysis, initiated by adipose triglyceride lipase (ATGL), and lipophagy. Each of these processes requires access to the LD surface to initiate LD TAG catabolism. Ablation of perilipin 2 (PLIN2), the most abundant lipid droplet-associated protein in steatotic liver, protects mice from diet-induced NAFLD. However, the mechanisms underlaying this protection are unclear. We tested the contributions of ATGL and lipophagy mediated lipolysis to reduced hepatic TAG in mice with liver-specific PLIN2 deficiency (PLIN2LKO) fed a Western-type diet for 12 weeks. We observed enhanced autophagy in the absence of PLIN2, as determined by ex vivo p62 flux, as well as increased p62- and LC3-positive autophagic vesicles in PLIN2LKO livers and isolated primary hepatocytes. Increased levels of autophagy correlated with significant increases in cellular fatty acid (FA) oxidation in PLIN2LKO hepatocytes. We observed that inhibition of either autophagy or ATGL blunted the increased FA oxidation in PLIN2LKO hepatocytes. Additionally, combined inhibition of ATGL and autophagy reduced FA oxidation to the same extent as treatment with either inhibitor alone. In sum, these studies show that protection against NAFLD in the absence of hepatic PLIN2 is driven by the integrated actions of both ATGL and lipophagy. View Full-Text
Keywords: perilipin; lipid droplet; autophagy; adipose tissue triglyceride lipase; non-alcoholic fatty liver disease perilipin; lipid droplet; autophagy; adipose tissue triglyceride lipase; non-alcoholic fatty liver disease
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MDPI and ACS Style

Griffin, J.D.; Bejarano, E.; Wang, X.-D.; Greenberg, A.S. Integrated Action of Autophagy and Adipose Tissue Triglyceride Lipase Ameliorates Diet-Induced Hepatic Steatosis in Liver-Specific PLIN2 Knockout Mice. Cells 2021, 10, 1016. https://doi.org/10.3390/cells10051016

AMA Style

Griffin JD, Bejarano E, Wang X-D, Greenberg AS. Integrated Action of Autophagy and Adipose Tissue Triglyceride Lipase Ameliorates Diet-Induced Hepatic Steatosis in Liver-Specific PLIN2 Knockout Mice. Cells. 2021; 10(5):1016. https://doi.org/10.3390/cells10051016

Chicago/Turabian Style

Griffin, John D., Eloy Bejarano, Xiang-Dong Wang, and Andrew S. Greenberg. 2021. "Integrated Action of Autophagy and Adipose Tissue Triglyceride Lipase Ameliorates Diet-Induced Hepatic Steatosis in Liver-Specific PLIN2 Knockout Mice" Cells 10, no. 5: 1016. https://doi.org/10.3390/cells10051016

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