ArticleThe Journal of clinical investigation2020
Parental metabolic syndrome epigenetically reprograms offspring hepatic lipid metabolism in mice.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 81 citations in OpenAlex.
- mNature metabolism · 2026Article
- Paternal Microplastic Exposure Alters Sperm Small Noncoding RNAs and Affects Offspring Metabolic Health in Mice.Journal of the Endocrine Society · 2026Article
- Unraveling Puerarin's impact on MRI hepatic lipid deposition and serum lipids in IUGR offspring rats.PloS one · 2026Article
- mAmerican journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Gut Microbiota Colonization in Early Life Influences Susceptibility to Adulthood Hepatic Lipid Accumulation in High-Fat-Diet-Fed Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD.JHEP reports : innovation in hepatology · 2025Article
- Multi-miRNAs-Mediated Hepatic Lepr Axis Suppression: A Pparg-Dicer1 Pathway-Driven Mechanism in Spermatogenesis for the Intergenerational Transmission of Paternal Metabolic Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Gestational hyperglycaemia impacts glucose control and insulin sensitivity in mouse offspring.Scientific reports · 2025Article
- Macrophage exosomal miR-30c-2-3p in atherosclerotic plaques aggravates microglial neuroinflammation during large-artery atherosclerotic stroke via TGF-β/SMAD2 pathway.Journal of neuroinflammation · 2024Article
- Sperm miR-142-3p Reprogramming Mediates Paternal Pre-Pregnancy Caffeine Exposure-Induced Non-Alcoholic Steatohepatitis in Male Offspring Rats.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- mCell metabolism · 2024Article
- Progress in the Study of Animal Models of Metabolic Dysfunction-Associated Steatotic Liver Disease.Nutrients · 2024Review
- Paternal hypercholesterolemia elicits sex-specific exacerbation of atherosclerosis in offspring.JCI insight · 2024Article
- Redox regulation of mNature cell biology · 2024Article
- Maternal Obesogenic Diet Attenuates Microbiome-Dependent Offspring Weaning Reaction with Worsening of Steatotic Liver Disease.The American journal of pathology · 2024Article
- Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in Offspring.Cellular and molecular gastroenterology and hepatology · 2024Article
- NREP contributes to development of NAFLD by regulating one-carbon metabolism in primary human hepatocytes.Cell chemical biology · 2023Article
- High-fat diet in early life triggers both reversible and persistent epigenetic changes in the medaka fish (Oryzias latipes).BMC genomics · 2023Article
- Hepatocyte nuclear factor 1A suppresses innate immune response by inducing degradation of TBK1 to inhibit steatohepatitis.Genes & diseases · 2023Article
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Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Although gene-environment interactions have been implicated in the etiology of several disorders, the impact of paternal and/or maternal metabolic syndrome on the clinical phenotypes of offspring and the underlying genetic and epigenetic contributors of NAFLD have not been fully explored. To this end, we used the liver-specific insulin receptor knockout (LIRKO) mouse, a unique nondietary model manifesting 3 hallmarks that confer high risk for the development of NAFLD: hyperglycemia, insulin resistance, and dyslipidemia. We report that parental metabolic syndrome epigenetically reprograms members of the TGF-β family, including neuronal regeneration-related protein (NREP) and growth differentiation factor 15 (GDF15). NREP and GDF15 modulate the expression of several genes involved in the regulation of hepatic lipid metabolism. In particular, NREP downregulation increases the protein abundance of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and ATP-citrate lyase (ACLY) in a TGF-β receptor/PI3K/protein kinase B-dependent manner, to regulate hepatic acetyl-CoA and cholesterol synthesis. Reduced hepatic expression of NREP in patients with NAFLD and substantial correlations between low serum NREP levels and the presence of steatosis and nonalcoholic steatohepatitis highlight the clinical translational relevance of our findings in the context of recent preclinical trials implicating ACLY in NAFLD progression.
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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.