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Intestinal MYC modulates obesity-related metabolic dysfunction
- Source :
- Nat Metab
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- MYC is a transcription factor with broad biological functions, notably in the control of cell proliferation. Here, we show that intestinal MYC regulates systemic metabolism. We find that MYC expression is increased in ileum biopsies from individuals with obesity and positively correlates with body mass index. Intestine-specific reduction of MYC in mice improves high-fat-diet-induced obesity, insulin resistance, hepatic steatosis and steatohepatitis. Mechanistically, reduced expression of MYC in the intestine promotes glucagon-like peptide-1 (GLP-1) production and secretion. Moreover, we identify Cers4, encoding ceramide synthase 4, catalysing de novo ceramide synthesis, as a MYC target gene. Finally, we show that administration of the MYC inhibitor 10058-F4 has beneficial effects on high-fat-diet-induced metabolic disorders, and is accompanied by increased GLP-1 and reduced ceramide levels in serum. This study positions intestinal MYC as a putative drug target against metabolic diseases, including non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.
- Subjects :
- Ceramide
Endocrinology, Diabetes and Metabolism
Biology
Diet, High-Fat
Article
Ilium
Proto-Oncogene Proteins c-myc
Mice
chemistry.chemical_compound
Insulin resistance
Glucagon-Like Peptide 1
Non-alcoholic Fatty Liver Disease
Physiology (medical)
Internal Medicine
medicine
Animals
Humans
Obesity
Intestinal Mucosa
Ceramide synthase
Transcription factor
Cell growth
Fatty liver
Cell Biology
medicine.disease
Disease Models, Animal
chemistry
Cancer research
Disease Susceptibility
Insulin Resistance
Steatosis
Steatohepatitis
Biomarkers
Subjects
Details
- ISSN :
- 25225812
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Nature Metabolism
- Accession number :
- edsair.doi.dedup.....4836a05529a76a99219096c48db1aa3a