PMID- 36244649 OWN - NLM STAT- MEDLINE DCOM- 20231106 LR - 20231113 IS - 2320-2890 (Electronic) IS - 2319-4170 (Print) IS - 2319-4170 (Linking) VI - 46 IP - 5 DP - 2023 Oct TI - The effects of intermittent hypoxia on hepatic expression of fatty acid translocase CD36 in lean and diet-induced obese mice. PG - 100566 LID - S2319-4170(22)00141-X [pii] LID - 10.1016/j.bj.2022.10.003 [doi] LID - 100566 AB - BACKGROUND: Both obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) are prevalent within obese individuals. We aimed to investigate the effects of intermittent hypoxia (IH), a clinical feature of OSA, on hepatic expression of fatty acid translocase (CD36) in relation to liver injury in lean and diet-induced obese mice. METHODS: Four-week-old male C57BL/6J mice were randomized to standard diet (SD) or high fat (HF) diet groups. At 13-week-old, all mice were exposed to either air or IH (IH30; thirty hypoxic episodes per hour) for four weeks. We assessed liver injury through lipid profile, oxidative and inflammatory stress, histological scoring and hepatic CD36 expression. RESULTS: In lean mice, IH elevated serum and hepatic triglyceride and free fatty acid (FFA) levels, in line with upregulation of hepatic CD36 expression and myeloperoxidase (MPO)-positive cells in support of inflammatory infiltrates along with increase in serum malondialdehyde (MDA), C-X-C motif chemokine ligand 1(CXCL-1) and monocyte chemoattractant protein-1 (MCP-1). In diet-induced obese mice, an increase in hepatic alanine transaminase (ALT) activity, serum and hepatic levels of lipid parameters and inflammatory markers, serum MDA level, hepatic expressions of CD36 and alpha-smooth muscle actin (alpha-SMA), and MPO-positive cells was observed. IH potentiated hepatic ALT activity, serum CXCL-1 and hepatic interleukin-6 (IL-6), in line with inflammatory infiltrates, but paradoxically, reduced hepatic FFA level and hepatic CD36 expression, compared to obese mice without IH exposure. However, IH further augmented diet-induced liver steatosis and fibrosis as shown by histological scores. CONCLUSION: This study contributes to support that IH featuring OSA may lead to liver injury via differential regulation of hepatic CD36 expression in lean and diet-induced obese mice. CI - Copyright (c) 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved. FAU - Ji, Yang AU - Ji Y AD - Respiratory Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. FAU - Liang, Yingmin AU - Liang Y AD - Respiratory Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Chu, Pak Hin AU - Chu PH AD - Department of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Ge, Mengqin AU - Ge M AD - Department of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Yeung, Sze Chun AU - Yeung SC AD - Department of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Ip, Mary Sau Man AU - Ip MSM AD - Respiratory Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China. FAU - Mak, Judith Choi Wo AU - Mak JCW AD - Respiratory Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Department of Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Pharmacology & Pharmacy, The University of Hong Kong, Hong Kong SAR, China. Electronic address: judithmak@hku.hk. LA - eng PT - Journal Article PT - Randomized Controlled Trial, Veterinary DEP - 20221013 PL - United States TA - Biomed J JT - Biomedical journal JID - 101599820 RN - 0 (Triglycerides) RN - 0 (Fatty Acids) SB - IM MH - Male MH - Mice MH - Animals MH - Mice, Obese MH - Mice, Inbred C57BL MH - *Liver/pathology MH - Hypoxia/metabolism/pathology MH - Diet, High-Fat/adverse effects MH - Triglycerides/metabolism MH - Fatty Acids/metabolism MH - *Sleep Apnea, Obstructive PMC - PMC10498409 OTO - NOTNLM OT - Inflammation OT - Intermittent hypoxia OT - Liver injury OT - Obstructive sleep apnea OT - Oxidative stress COIS- Conflicts of interest The authors have no Conflicts of interest to declare. EDAT- 2022/10/17 06:00 MHDA- 2023/11/06 06:41 PMCR- 2022/10/13 CRDT- 2022/10/16 19:47 PHST- 2022/01/21 00:00 [received] PHST- 2022/09/01 00:00 [revised] PHST- 2022/10/11 00:00 [accepted] PHST- 2023/11/06 06:41 [medline] PHST- 2022/10/17 06:00 [pubmed] PHST- 2022/10/16 19:47 [entrez] PHST- 2022/10/13 00:00 [pmc-release] AID - S2319-4170(22)00141-X [pii] AID - 100566 [pii] AID - 10.1016/j.bj.2022.10.003 [doi] PST - ppublish SO - Biomed J. 2023 Oct;46(5):100566. doi: 10.1016/j.bj.2022.10.003. Epub 2022 Oct 13.