Upstream regulators of apoptosis mediates methionine-induced changes of lipid metabolism |
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| Affiliation: | 1. Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan 430070, China;2. Collaborative Innovation Center for Efficient and Health Production of Fisheries in Hunan Province, Changde 415000, China;3. Diabetes and Nutritional Sciences Division, School of Medicine, King''s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK;1. Department of Biology, Faculty of Marine and Environmental Sciences, Instituto Universitario de Investigación Marina (INMAR), Universidad de Cádiz, Campus de Excelencia Internacional del Mar (CEI·MAR), Av. República Saharaui s/n, E-11510 Puerto Real, Cádiz, Spain;2. Radboud University, Institute for Water and Wetland Research, Department of Animal Ecology and Physiology, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands;1. Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), & Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, PR China;2. Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Wen hai Road, Qingdao, Shandong, 266237, PR China |
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| Abstract: | Although the role of methionine (Met), as precursor for l-carnitine synthesis, in the regulation of lipid metabolism has been explored. Met seems to have tissue- and species-specific regulatory effect on lipid metabolism, implying that the mechanisms in Met regulation of lipid metabolism is complex and may involve the upstream regulatory pathway of lipid metabolism. The present study was performed to determine the mechanism of apoptosis signaling pathways mediating Met-induced changes of hepatic lipid deposition and metabolism in fish, and compare the differences of the mechanisms between the fish and mammals. By iTRAQ-based quantitative proteome analyses, we found that both dietary Met deficiency and excess evoked apoptosis signaling pathways, increased hepatic lipid deposition and caused aberrant hepatic lipid metabolism of yellow catfish Pelteobagrus fulvidraco. Using primary hepatocytes from P. fulvidraco, inhibition of caspase by Z-VAD-FMK blocked the apoptotic signaling pathways with a concomitant reversal of Met deficiency- and excess-induced increase of lipid deposition, indicating that apoptosis involved the Met-mediated changes of hepatic lipid metabolism. Moreover, we explored the roles of three upstream apoptotic signaling pathways (PI3K/AKT-TOR pathway, cAMP/PKA/CREB pathway and LKB1/AMPK-FOXO pathway) influencing hepatic lipid metabolism of P. fulvidraco. The three upstream pathways participated in apoptosis mediating Met-induced changes of lipid metabolism in P. fulvidraco. At last, HepG2 cell line was used to compare the similarities of mechanisms in apoptosis mediating Met-induced changes of lipid metabolism between fish and mammals. Although several slight differences existed, apoptosis mediated the Met-induced changes of lipid metabolism between fish and mammals. The present study reveals novel apoptosis-relevant signal transduction axis which mediates the Met-induced changes of lipid metabolism, which will help understand the mechanistic link between apoptosis and lipid metabolism, and highlight the importance of the evolutionary conservative apoptosis signaling axis in regulating Met–induced changes of hepatic lipid metabolism. |
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