ArticleThe Journal of endocrinology2021
GH directly inhibits steatosis and liver injury in a sex-dependent and IGF1-independent manner.
Article in The Journal of endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Pooled it
- Acromegaly and Metabolic Dysfunction-Associated Steatotic Liver Disease: Clinical and Therapeutic Implications.Current obesity reports · 2026Review
- Hypothalamic Control of Liver Health and Disease: From Circuits to Pathophysiology and Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Growing Pains: GH-induced Fibrosis Across Multiple Organs in bGH Mice.Endocrinology · 2025Article
- Low Liver-Derived IGF-1 Drives the Alterations in Growth Hormone Secretion in Food-Restricted Male Mice.Endocrinology · 2025Article
- Liver injury severity determines skeletal deterioration: a shared pathophysiological axis between MASLD and osteoarthritis.GeroScience · 2025Article
- Liver-specific actions of GH and IGF1 that protect against MASLD.Nature reviews. Endocrinology · 2025 · on this mapReview
- Sexual dimorphism in the effects of maternal adipose tissue growth hormone receptor deficiency on offspring metabolic health.Biology of sex differences · 2024Article
- Modifications of the GH Axis Reveal Unique Sexually Dimorphic Liver Signatures forJournal of the Endocrine Society · 2024Article
- Case report: Pediatric hepatopulmonary syndrome despite strict weight control after craniopharyngioma surgery.Frontiers in endocrinology · 2024Article
- Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver disease.Frontiers in cell and developmental biology · 2024Article
- miR136 regulates proliferation and differentiation of small tail han sheep preadipocytes.Adipocyte · 2023Article
- Direct and systemic actions of growth hormone receptor (GHR)-signaling on hepatic glycolysis, de novo lipogenesis and insulin sensitivity, associated with steatosis.Metabolism: clinical and experimental · 2023Article
- Liver insulin-like growth factor-1 mediates effects of low-intensity vibration on wound healing in diabetic mice.The Journal of pathology · 2023Article
- Chromosomal and gonadal sex drive sex differences in lipids and hepatic gene expression in response to hypercholesterolemia and statin treatment.Biology of sex differences · 2022Article
- Expression of IGF-1 receptor and GH receptor in hepatic tissue of patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 2022Article
- Growth Hormone and Insulin-Like Growth Factor 1 Regulation of Nonalcoholic Fatty Liver Disease.The Journal of clinical endocrinology and metabolism · 2022 · on this mapReview
- Liver is a primary source of insulin-like growth factor-1 in skin wound healing.The Journal of endocrinology · 2021Article
- Emerging Role of Genomic Analysis in Clinical Evaluation of Lean Individuals With NAFLD.Hepatology (Baltimore, Md.) · 2021Review
- Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
A reduction in hepatocyte growth hormone (GH)-signaling promotes non-alcoholic fatty liver disease (NAFLD). However, debate remains as to the relative contribution of the direct effects of GH on hepatocyte function vs indirect effects, via alterations in insulin-like growth factor 1 (IGF1). To isolate the role of hepatocyte GH receptor (GHR) signaling, independent of changes in IGF1, mice with adult-onset, hepatocyte-specific GHR knockdown (aHepGHRkd) were treated with a vector expressing rat IGF1 targeted specifically to hepatocytes. Compared to GHR-intact mice, aHepGHRkd reduced circulating IGF1 and elevated GH. In male aHepGHRkd, the shift in IGF1/GH did not alter plasma glucose or non-esterified fatty acids (NEFA), but was associated with increased insulin, enhanced systemic lipid oxidation and reduced white adipose tissue (WAT) mass. Livers of male aHepGHRkd exhibited steatosis associated with increased de novo lipogenesis, hepatocyte ballooning and inflammation. In female aHepGHRkd, hepatic GHR protein levels were not detectable, but moderate levels of IGF1 were maintained, with minimal alterations in systemic metabolism and no evidence of steatosis. Reconstitution of hepatocyte IGF1 in male aHepGHRkd lowered GH and normalized insulin, whole body lipid utilization and WAT mass. However, IGF1 reconstitution did not reduce steatosis or eliminate liver injury. RNAseq analysis showed IGF1 reconstitution did not impact aHepGHRkd-induced changes in liver gene expression, despite changes in systemic metabolism. These results demonstrate the impact of aHepGHRkd is sexually dimorphic and the steatosis and liver injury observed in male aHepGHRkd mice is autonomous of IGF1, suggesting GH acts directly on the adult hepatocyte to control NAFLD progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.