Their study characterizes the role of adiponectin in the development of age-related liver fibrosis. Dr. Zhao is an assistant professor in the Department of Medicine, Division of Endocrinology and an investigator with the Sam and Ann Barshop Institute for Longevity and Aging Studies.
The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis
Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M Kusminski, Terry D Hinds Jr, Philipp E Scherer
Cell Rep. 2025 Jan 28;44(1):115165. doi: 10.1016/j.celrep.2024.115165. Epub 2025 Jan 9.
Abstract:
Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated HSC-specific adiponectin overexpression and null models that demonstrate that HSC-specific adiponectin overexpression dramatically reduces liver fibrosis, whereas HSC-specific adiponectin elimination accelerates fibrosis progression. We identify a local adiponectin-peroxisome proliferator-activated receptor gamma (PPARγ) axis in HSCs that exerts a marked influence on the progression of local fibrosis, independent of circulating adiponectin derived from adipocytes.
Keywords: CP: Metabolism; PPARγ; adiponectin; liver fibrosis; obesity.