Changes in retinoid metabolism and signaling associated with metabolic remodeling during fasting and in type I diabetes
| Autor: | Olga V. Belyaeva, Wojciech Krezel, Kelli R. Goggans, Kirill M. Popov, Natalia Y. Kedishvili, Alla Klyuyeva |
|---|---|
| Přispěvatelé: | University of Alabama at Birmingham [ Birmingham] (UAB), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), univOAK, Archive ouverte |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
NADPH nicotinamide adenine dinucleotide phosphate hydrogen lipid droplets Retinoic acid Biochemistry vitamin A Mice chemistry.chemical_compound Lipid droplet Glucokinase RA retinoic acid retinoic acid biology Chemistry Fatty acid synthase dehydrogenase Microsomes Liver SDR short-chain dehydrogenase/reductase Phosphoenolpyruvate carboxykinase Research Article Signal Transduction retinol medicine.medical_specialty fasting Tretinoin liver Gene Expression Regulation Enzymologic Retinoids 03 medical and health sciences Carnitine palmitoyltransferase 1 Downregulation and upregulation Internal medicine medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RDH retinol dehydrogenase Molecular Biology RDH10 Carnitine O-Palmitoyltransferase 030102 biochemistry & molecular biology Lipid metabolism Cell Biology DHRS3 Alcohol Oxidoreductases Disease Models Animal Diabetes Mellitus Type 1 Metabolism 030104 developmental biology Endocrinology reductase biology.protein Phosphoenolpyruvate Carboxykinase (ATP) |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, 2021, 296, ⟨10.1016/j.jbc.2021.100323⟩ The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| DOI: | 10.1016/j.jbc.2021.100323⟩ |
| Popis: | Liver is the central metabolic hub that coordinates carbohydrate and lipid metabolism. The bioactive derivative of vitamin A, retinoic acid (RA), was shown to regulate major metabolic genes including phosphoenolpyruvate carboxykinase, fatty acid synthase, carnitine palmitoyltransferase 1, and glucokinase among others. Expression levels of these genes undergo profound changes during adaptation to fasting or in metabolic diseases such as type 1 diabetes (T1D). However, it is unknown whether the levels of hepatic RA change during metabolic remodeling. This study investigated the dynamics of hepatic retinoid metabolism and signaling in the fed state, in fasting, and in T1D. Our results show that fed-to-fasted transition is associated with significant decrease in hepatic retinol dehydrogenase (RDH) activity, the rate-limiting step in RA biosynthesis, and downregulation of RA signaling. The decrease in RDH activity correlates with the decreased abundance and altered subcellular distribution of RDH10 while Rdh10 transcript levels remain unchanged. In contrast to fasting, untreated T1D is associated with upregulation of RA signaling and an increase in hepatic RDH activity, which correlates with the increased abundance of RDH10 in microsomal membranes. The dynamic changes in RDH10 protein levels in the absence of changes in its transcript levels imply the existence of posttranscriptional regulation of RDH10 protein. Together, these data suggest that the downregulation of hepatic RA biosynthesis, in part via the decrease in RDH10, is an integral component of adaptation to fasting. In contrast, the upregulation of hepatic RA biosynthesis and signaling in T1D might contribute to metabolic inflexibility associated with this disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|