Year: 2025
Type: article
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.
Source: Cell Reports
Institutions: The University of Texas at San Antonio Health Science Center, The University of Texas Southwestern Medical Center, University of Kentucky, Wuhan University, The University of Osaka, Tianjin Medical University General Hospital, Tianjin Medical University, Baylor College of Medicine, Children's Nutrition Research Center at Baylor College of Medicine
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: G1218708297, PAQR4 as a Novel Target in NASH and Cardiovascular Diseases, G154349642, G1802610678, G1821512284, The exploration of the roles of fibrotic signals in adipocytes and pre-adipocytes, G2342415576, G239890624, G3791799676, G4386756897, G5290824047, G58964009, G600581782, G606616135, Adiponectin, A Protein Secreted From Adipose Tissue, Generation of Novel Genetic Tools to Study Cellular Heterogeneity in Adipose Tissues, Paracrine effects of leptin in regulating visceral fat expansion, G7545275864, G9000103934, G9000189844, G9000274628, A New Perspective on Leptin in Health and Disease, UT Southwestern NORC, Competing Renewal P01, Impact of a Novel Secreted Enzyme J18 on Healthspan and Lifespan, Enhancing metabolic action of FGF21 through adipocyte Connexin43 gap junction channels, Effects of leptin modulation on health span and lifespan, Physiological Role of Dedifferentiating Dermal Adipose Tissue
OpenAlex ID: W4406219004