PMID- 36028098 OWN - NLM STAT- MEDLINE DCOM- 20221101 LR - 20230112 IS - 1873-4847 (Electronic) IS - 0955-2863 (Linking) VI - 110 DP - 2022 Dec TI - Intermittent fasting attenuates lipopolysaccharide-induced acute lung injury in mice by modulating macrophage polarization. PG - 109133 LID - S0955-2863(22)00201-7 [pii] LID - 10.1016/j.jnutbio.2022.109133 [doi] AB - Acute lung injury (ALI) is a spectrum of acute and life-threatening pulmonary inflammatory conditions. Treatment of ALI remains a clinical challenge. Recently, intermittent fasting (IF) has been shown to improve health and alleviate many diseases. In this study, we tested whether IF attenuated ALI and investigated the mechanism underlying this process. In vivo, the effects of IF on ALI were evaluated in a lipopolysaccharide (LPS)-induced murine ALI model. We found that two times of 24-h fasting in a week before ALI efficiently ameliorated LPS-induced lung injury in mice, characterized by alleviated lung lesions, wet-to-dry weight ratio, myeloperoxidase activity, malondialdehyde content, and lower levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta. In vitro, functional assays were conducted to assess IF on the inflammatory response and macrophage polarization of bone marrow-derived macrophages (BMDMs) treated with LPS or IL-4. And PPARgamma antagonist GW9662 and AMPK siRNA were used to test the role of PPARgamma and AMPK in the IF-mediated improvement of ALI. The results showed that IF (serum deprivation) suppressed macrophage M1 activation and promoted M2 activation in LPS-treated BMDMs. While, IF also augmented macrophage M2 polarization in IL-4-treated BMDMs. Further mechanistic studies showed that the promotive effect of IF on M2 polarization was related to the activation of the PPARgamma and AMPK pathways. In conclusion, this study suggests that IF enhances M2 polarization by activating the AMPK and PPARgamma pathways, thus facilitating anti-inflammatory response and ameliorating ALI. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Ma, Li AU - Ma L AD - Department of Anesthesiology, Liuzhou People's Hospital, Liuzhou, Guangxi, 545006, China. FAU - Chen, Yan-Qing AU - Chen YQ AD - Department of Anesthesiology, Liuzhou People's Hospital, Liuzhou, Guangxi, 545006, China. FAU - You, Zhi-Jian AU - You ZJ AD - Department of Anesthesiology, Liuzhou People's Hospital, Liuzhou, Guangxi, 545006, China. FAU - Jiang, Zhong-Sheng AU - Jiang ZS AD - Department of Infection, Liuzhou People's Hospital, Liuzhou, Guangxi, 545001, China. FAU - Fang, Yu AU - Fang Y AD - Medical laboratory and Pathology Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410021, China. Electronic address: fangyu.stone@163.com. FAU - Dong, Liang AU - Dong L AD - Department of Anesthesiology, Liuzhou People's Hospital, Liuzhou, Guangxi, 545006, China. Electronic address: donglqqsx2008@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220824 PL - United States TA - J Nutr Biochem JT - The Journal of nutritional biochemistry JID - 9010081 RN - 0 (Lipopolysaccharides) RN - 0 (PPAR gamma) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - 207137-56-2 (Interleukin-4) SB - IM MH - Mice MH - Animals MH - *Lipopolysaccharides/metabolism MH - Fasting MH - PPAR gamma/metabolism MH - AMP-Activated Protein Kinases/metabolism MH - Interleukin-4/metabolism/pharmacology/therapeutic use MH - *Acute Lung Injury/chemically induced MH - Macrophages/metabolism MH - Lung OTO - NOTNLM OT - AMPK OT - Acute lung injury OT - PPARgamma OT - intermittent fasting OT - macrophage polarization EDAT- 2022/08/27 06:00 MHDA- 2022/11/02 06:00 CRDT- 2022/08/26 19:25 PHST- 2022/01/09 00:00 [received] PHST- 2022/05/14 00:00 [revised] PHST- 2022/08/02 00:00 [accepted] PHST- 2022/08/27 06:00 [pubmed] PHST- 2022/11/02 06:00 [medline] PHST- 2022/08/26 19:25 [entrez] AID - S0955-2863(22)00201-7 [pii] AID - 10.1016/j.jnutbio.2022.109133 [doi] PST - ppublish SO - J Nutr Biochem. 2022 Dec;110:109133. doi: 10.1016/j.jnutbio.2022.109133. Epub 2022 Aug 24.