1. Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase.
- Author
-
Pajed L, Taschler U, Tilp A, Hofer P, Kotzbeck P, Kolleritsch S, Radner FPW, Pototschnig I, Wagner C, Schratter M, Eder S, Huetter S, Schreiber R, Haemmerle G, Eichmann TO, Schweiger M, Hoefler G, Kershaw EE, Lass A, and Schoiswohl G
- Subjects
- Adipocytes pathology, Age Factors, Animals, Blood Glucose metabolism, Disease Models, Animal, Fatty Liver genetics, Fatty Liver pathology, Insulin metabolism, Lipodystrophy genetics, Lipodystrophy pathology, Liver pathology, Male, Mice, Inbred C57BL, Mice, Knockout, PPAR gamma metabolism, Sterol Esterase genetics, Time Factors, Mice, Adipocytes enzymology, Energy Metabolism, Fatty Liver enzymology, Lipodystrophy enzymology, Lipolysis, Liver metabolism, Sterol Esterase deficiency
- Abstract
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.
- Published
- 2021
- Full Text
- View/download PDF