SIRT4 is an early regulator of branched-chain amino acid catabolism that promotes adipogenesis
| Autor: | Sarah A. Tucker, Giulia Notarangelo, Clary B. Clish, Haejin Yoon, Robert A. H. van de Ven, Mathew T. Chvasta, Gaëlle Laurent, Jessica B. Spinelli, Elizabeth R. Nunn, Marcia C. Haigis, Shakchhi Joshi, Stacy Mulei, Krystle Kalafut, Suganja Sivaloganathan, Paulina Keskinidis, Elma Zaganjor |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Peroxisome proliferator-activated receptor gamma
BCAA catabolism QH301-705.5 Branched-chain amino acid Adipose tissue General Biochemistry Genetics and Molecular Biology Article Diabetes Mellitus Experimental adipogenesis Mitochondrial Proteins chemistry.chemical_compound Mice SIRT4 Adipocyte 3T3-L1 Cells Animals Sirtuins Biology (General) amino acids biology Catabolism Chemistry differentiation Peroxisome Cell biology Mice Inbred C57BL PPAR gamma Disease Models Animal sirtuin Adipose Tissue Adipogenesis Sirtuin biology.protein Amino Acids Branched-Chain |
| Zdroj: | Cell Reports, Vol 36, Iss 2, Pp 109345-(2021) Cell Rep |
| ISSN: | 2211-1247 |
| Popis: | Summary: Upon nutrient stimulation, pre-adipocytes undergo differentiation to transform into mature adipocytes capable of storing nutrients as fat. We profiled cellular metabolite consumption to identify early metabolic drivers of adipocyte differentiation. We find that adipocyte differentiation raises the uptake and consumption of numerous amino acids. In particular, branched-chain amino acid (BCAA) catabolism precedes and promotes peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of adipogenesis. In early adipogenesis, the mitochondrial sirtuin SIRT4 elevates BCAA catabolism through the activation of methylcrotonyl-coenzyme A (CoA) carboxylase (MCCC). MCCC supports leucine oxidation by catalyzing the carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA. Sirtuin 4 (SIRT4) expression is decreased in adipose tissue of numerous diabetic mouse models, and its expression is most correlated with BCAA enzymes, suggesting a potential role for SIRT4 in adipose pathology through the alteration of BCAA metabolism. In summary, this work provides a temporal analysis of adipocyte differentiation and uncovers early metabolic events that stimulate transcriptional reprogramming. |
| Databáze: | OpenAIRE |
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