PMID- 29103907 OWN - NLM STAT- MEDLINE DCOM- 20190415 LR - 20210225 IS - 1871-403X (Print) IS - 1871-403X (Linking) VI - 12 IP - 2 DP - 2018 Mar-Apr TI - Myeloid ATG16L1 does not affect adipose tissue inflammation or body mass in mice fed high fat diet. PG - 174-186 LID - S1871-403X(17)30118-7 [pii] LID - 10.1016/j.orcp.2017.10.006 [doi] AB - BACKGROUND: An influx of lipid-loaded macrophages characterizes visceral adipose tissue (VAT) inflammation, which is an important factor in the development of insulin resistance (IR) in obesity. Depletion of macrophage lipids accompanies increased whole body insulin sensitivity, but the underlying mechanism is unknown. Deficiency of autophagy protein ATG16L1 is associated with increases in inflammatory diseases and lipid metabolism, but the connection between ATG16L1, IR, and obesity remains elusive. We hypothesize that myeloid ATG16L1 contributes to lipid loading in macrophages and to IR. METHODS: Wild-type (WT) bone marrow derived macrophages (BMDMs) were treated with fatty acids and assessed for markers of autophagy. Myeloid-deficient Atg16l1 and littermate control male mice were fed high fat diet (HFD) or low fat diet (LFD) for 3 months starting at 8 weeks of age. Mice were assessed for body mass, fat and lean mass, glucose and insulin sensitivity, food consumption and adipose inflammation. Fluorescence-activated cell sorted VAT macrophages were assessed for lipid content and expression of autophagy related genes. RESULTS: VAT and VAT macrophages from HFD-fed WT mice did not show differences in autophagy protein and gene expression compared to tissue from LFD-fed mice. Fatty acid-treated BMDMs increased neutral lipid content but did not change autophagy protein expression. HFD-fed Atg16l1 myeloid-deficient and littermate mice demonstrated no differences in body mass, glucose or insulin sensitivity, food consumption, fat or lean mass, macrophage lipid content, or adipose tissue inflammation. CONCLUSION: ATG16L1 does not contribute to obesity, IR, adipose tissue inflammation or lipid loading in macrophages in mice fed HFD. CI - Copyright (c) 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved. FAU - Litwinoff, Evelyn M S AU - Litwinoff EMS AD - Diabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Langone Health, New York, NY 10016, USA. FAU - Gold, Merav Y AU - Gold MY AD - Diabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Langone Health, New York, NY 10016, USA. FAU - Singh, Karan AU - Singh K AD - Diabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Langone Health, New York, NY 10016, USA. FAU - Hu, Jiyuan AU - Hu J AD - Departments of Population Health (Biostatistics) and Environmental Medicine, NYU Langone Health, New York, NY 10016, USA. FAU - Li, Huilin AU - Li H AD - Departments of Population Health (Biostatistics) and Environmental Medicine, NYU Langone Health, New York, NY 10016, USA. FAU - Cadwell, Ken AU - Cadwell K AD - Kimmel Center for Biology and Medicine at the Skirball Institute, and the Department of Microbiology, NYU Langone Health, New York, NY 10016, USA. FAU - Schmidt, Ann Marie AU - Schmidt AM AD - Kimmel Center for Biology and Medicine at the Skirball Institute, and the Department of Microbiology, NYU Langone Health, New York, NY 10016, USA. Electronic address: Annmarie.Schmidt@nyumc.org. LA - eng GR - P01 HL131481/HL/NHLBI NIH HHS/United States GR - P30 CA016087/CA/NCI NIH HHS/United States GR - R01 DK109675/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20171102 PL - Netherlands TA - Obes Res Clin Pract JT - Obesity research & clinical practice JID - 101303911 RN - 0 (Atg16l1 protein, mouse) RN - 0 (Autophagy-Related Proteins) RN - 0 (Carrier Proteins) RN - 0 (Fatty Acids) SB - IM MH - Adipose Tissue/*pathology MH - Animals MH - Autophagy-Related Proteins MH - Carrier Proteins/*physiology MH - *Diet, High-Fat MH - Disease Models, Animal MH - Energy Intake MH - Fatty Acids MH - Gene Expression Regulation MH - Inflammation/*genetics/*pathology MH - Lipid Metabolism/genetics MH - Macrophages/*physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Obesity/genetics/pathology PMC - PMC5932285 MID - NIHMS917225 OTO - NOTNLM OT - Adipose tissue OT - Autophagy OT - Inflammation OT - Obesity EDAT- 2017/11/07 06:00 MHDA- 2019/04/16 06:00 PMCR- 2019/03/01 CRDT- 2017/11/07 06:00 PHST- 2017/05/26 00:00 [received] PHST- 2017/10/04 00:00 [revised] PHST- 2017/10/17 00:00 [accepted] PHST- 2017/11/07 06:00 [pubmed] PHST- 2019/04/16 06:00 [medline] PHST- 2017/11/07 06:00 [entrez] PHST- 2019/03/01 00:00 [pmc-release] AID - S1871-403X(17)30118-7 [pii] AID - 10.1016/j.orcp.2017.10.006 [doi] PST - ppublish SO - Obes Res Clin Pract. 2018 Mar-Apr;12(2):174-186. doi: 10.1016/j.orcp.2017.10.006. Epub 2017 Nov 2.