Intestinal MYC modulates obesity-related metabolic dysfunction
| Autor: | Weiwei Liu, Yuhong Luo, Cen Xie, Frank J. Gonzalez, Oksana Gavrilova, Shoumei Yang, Henrique Bregolin Dias, Xuan Wu, Changtao Jiang, Xiaozhen Guo, Jie Cai, Kristopher W. Krausz, Shogo Takahashi, Lulu Sun |
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| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Nat Metab |
| ISSN: | 2522-5812 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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