Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast
| Autor: | Thomas Nielsen, Steen B. Pedersen, Jens Otto Lunde Jørgensen, Niels Møller, Jørgen Rungby, Niels Jessen, Ann Mosegaard Bak, Rikke Viggers, Andreas Buch Møller, Mikkel H. Vendelbo |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Time Factors Physiology Endocrinology Diabetes and Metabolism Protein metabolism Adipose tissue Muscle Proteins Cell Cycle Proteins Tripartite Motif Proteins chemistry.chemical_compound 0302 clinical medicine Autophagy-Related Protein-1 Homolog Urea Phosphorylation Cross-Over Studies TOR Serine-Threonine Kinases Intracellular Signaling Peptides and Proteins Fasting 1-Acylglycerol-3-Phosphate O-Acyltransferase Protein catabolism Forearm medicine.anatomical_structure Adipose Tissue Adult medicine.medical_specialty Lipolysis Ubiquitin-Protein Ligases 030209 endocrinology & metabolism Biology 03 medical and health sciences Young Adult Physiology (medical) Internal medicine medicine Humans Obesity RNA Messenger Muscle Skeletal Catabolism Skeletal muscle Lipid metabolism Lipase Sterol Esterase Lipid Metabolism 030104 developmental biology Endocrinology chemistry Case-Control Studies Adipose triglyceride lipase |
| Zdroj: | Bak, A M, Møller, A B, Vendelbo, M H, Nielsen, T S, Viggers, R, Rungby, J, Pedersen, S B, Jørgensen, J O L, Jessen, N & Møller, N 2016, ' Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast ', American Journal of Physiology: Endocrinology and Metabolism, vol. 311, no. 1, pp. E224-35 . https://doi.org/10.1152/ajpendo.00464.2015 |
| DOI: | 10.1152/ajpendo.00464.2015 |
| Popis: | Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading to increased lipolysis and 2) whether this scenario is associated with decreased amino acid and urea fluxes, and decreased muscle amino acid release in obese subjects under basal and fasting conditions. We therefore studied nine lean and nine obese subjects twice, after 12 and 72 h of fasting, using measurements of mRNA and protein expression and phosphorylation of lipolytic and protein metabolic signaling molecules in fat and muscle together with whole body and forearm tracer techniques. Obese subjects displayed increased whole body lipolysis, decreased urea production rates, and decreased forearm muscle protein breakdown per 100 ml of forearm tissue, differences that persisted after 72 h of fasting. Lipolysis per fat mass unit was reduced in obese subjects and, correspondingly, adipose tissue hormone-sensitive lipase (HSL) phosphorylation and mRNA and protein levels of the adipose triglyceride lipase (ATGL) coactivator CGI58 were decreased. Fasting resulted in higher HSL phosphorylations and lower protein levels of the ATGL inhibitor G0S2. Muscle protein expressions of mammalian target of rapamycin (mTOR) and 4EBP1 were lower in obese subjects, and MuRf1 mRNA was higher with fasting in lean but not obese subjects. Phosphorylation and signaling of mTOR decreased with fasting in both groups, whereas ULK1 protein and mRNA levels increased. In summary, obese subjects exhibit increased lipolysis due to a large fat mass with blunted prolipolytic signaling, together with decreased urea and amino acid fluxes both in the basal and 72-h fasted state; this is compatible with preservation of muscle and whole body protein. |
| Databáze: | OpenAIRE |
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