Usage Information
Abstract
Nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are liver manifestations of the metabolic syndrome and can progress to hepatocellular carcinoma (HCC). Loss of growth hormone (GH) signaling is reported to predispose to NAFLD and NASH through direct actions on the liver. Here, we report that aged mice lacking hepatocyte Jak2 (JAK2L), an obligate transducer of GH signaling, spontaneously develop the full spectrum of phenotypes found in patients with metabolic liver disease, beginning with insulin resistance and lipodystrophy and manifesting as NAFLD, NASH, and even HCC, independent of dietary intervention. Remarkably, insulin resistance, metabolic liver disease, and carcinogenesis are prevented in JAK2L mice via concomitant deletion of adipocyte Jak2. Further, we demonstrate that GH increases hepatic lipid burden but does so indirectly via signaling through adipocyte JAK2. Collectively, these data establish adipocytes as the mediator of GH-induced metabolic liver disease and carcinogenesis. In addition, we report what we believe to be a new spontaneous model of NAFLD, NASH, and HCC that recapitulates the natural sequelae of human insulin resistance–associated disease progression. The work presented here suggests that attention be paid to inhibition of adipocyte GH signaling as a therapeutic target of metabolic liver disease.
Authors
Kevin C. Corbit, Camella G. Wilson, Dylan Lowe, Jennifer L. Tran, Nicholas B. Vera, Michelle Clasquin, Aras N. Mattis, Ethan J. Weiss
Usage data is cumulative from April 2025 through April 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 986 | 76 |
| 125 | 30 | |
| Figure | 233 | 1 |
| Supplemental data | 52 | 2 |
| Citation downloads | 98 | 0 |
| Totals | 1,494 | 109 |
| Total Views | 1,603 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
