ArticleCell death & disease2022
Long-term oral administration of an HNF4α agonist prevents weight gain and hepatic steatosis by promoting increased mitochondrial mass and function.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Review
- Hnf4α integrates AIF and caspase 3/9 signaling to restrict single and coinfecting pathogens in teleosts.PLoS pathogens · 2025Article
- Phytochemical Characterization and Anti-Molecules (Basel, Switzerland) · 2025Article
- Orphan Nuclear Receptors in Metabolic Dysfunction-associated Steatotic Liver Disease Development.Journal of clinical and translational hepatology · 2025Review
- Macrophage fatty acid metabolism under chronic hypoxia shapes γδ T cell recruitment via CCL22.iScience · 2025Article
- Nicotinamide phosphoribosyltransferase in NADCell death discovery · 2025Review
- Opaganib Promotes Weight Loss and Suppresses High-Fat Diet-Induced Obesity and Glucose Intolerance.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- HNF4α contributes to hepatic CAR dysfunction in polymicrobial sepsis.Frontiers in immunology · 2025Article
- A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.EMBO molecular medicine · 2024Article
- Restricting bioenergetic efficiency enhances longevity and mitochondrial redox capacity in Drosophila melanogaster.Aging cell · 2024Article
- Perspective: Nutrition's Next Chapter - Bioactive Gaps and the Microbiome-Mitochondria Axis.Advances in nutrition (Bethesda, Md.) · 2023Article
- Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease.International journal of biological sciences · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report here that the potent HNF4α agonist N-trans-caffeoyltyramine (NCT) promotes weight loss by inducing an increase in mitochondrial mass and function, including fatty acid oxidation. Previously, we found in a short term trial in obese mice that NCT promoted reversal of hepatic steatosis through a mechanism involving the stimulation of lipophagy by dihydroceramides. NCT led to increased dihydroceramide levels by inhibiting dihydroceramide conversion to ceramides. Here, we were able to administer NCT orally, permitting longer term administration. Mice fed NCT mixed with high fat diet exhibited decreased weight. Examination of RNA-seq data revealed an increase in PPARGC1A, a central regulator of mitochondrial biogenesis. In addition to the decreased hepatic steatosis that we found previously, mice fed a high fat diet containing NCT mice weighed substantially less than control mice fed high fat diet alone. They had increased mitochondrial mass, exhibited increased fatty acid oxidation, and had an increased level of NAD. Markers of liver inflammation such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), which are important in the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis were decreased by NCT. There was no evidence of any toxicity from NCT consumption. These results indicate that HNF4α is an important regulator of mitochondrial mass and function and support that use of HNF4α to treat disorders of fatty acid excess, potentially including obesity, NAFLD, and NASH.
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