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Publication : Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase.

First Author  Pajed L Year  2021
Journal  Commun Biol Volume  4
Issue  1 Pages  323
PubMed ID  33692445 Mgi Jnum  J:317175
Mgi Id  MGI:6714969 Doi  10.1038/s42003-021-01858-z
Citation  Pajed L, et al. (2021) Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase. Commun Biol 4(1):323
abstractText  Modulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy.
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