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The present study tested the hypothesis that CS can divert lipid deposition to muscles to offset the supposed benefit of reduced body weight gain on insulin signalling in this major site for glucose tolerance (or insulin action). The study was conducted in mice exposed to chronic CS followed by either a chow (CH) diet or a high-fat (HF) diet. CS increased triglyceride (TG) levels in both plasma and muscle despite a reduced body weight gain and adiposity. CS led to glucose intolerance in CH-fed mice and they retained the glucose intolerance that was induced by the HF diet. In adipose tissue, CS increased macrophage infiltration and the mRNA expression of TNF\u03b1 but suppressed the protein expression of adipose triglyceride lipase and PPAR\u03b3. While CS increased hormone-sensitive lipase and suppressed the mRNA expression of leptin, these effects were blunted in HF-fed mice. These results imply that CS impairs insulin signalling in skeletal muscle via accumulated intramuscular lipids from lipolysis and lipodystrophy of adipose tissues. This may explain why smokers may not benefit from insulin sensitising effects of reduced body weight gain.<\/jats:p>","DOI":"10.1042\/cs20200173","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T13:19:26Z","timestamp":1592918366000},"page":"1659-1673","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cigarette smoking blocks the benefit from reduced weight gain for insulin action by shifting lipids deposition to muscle"],"prefix":"10.1042","volume":"134","author":[{"given":"Anwar","family":"Khan","sequence":"first","affiliation":[{"name":"Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherouk","family":"Fouda","sequence":"additional","affiliation":[{"name":"Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Mahzari","sequence":"additional","affiliation":[{"name":"Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia"},{"name":"Laboratory Medicine Department, Faculty of Applied Medicine, Albaha University, Albaha, KSA, Kingdom of Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley\u00a0M.H.","family":"Chan","sequence":"additional","affiliation":[{"name":"Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cherubina","family":"Ratnam","sequence":"additional","affiliation":[{"name":"Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8443-7071","authenticated-orcid":false,"given":"Ross","family":"Vlahos","sequence":"additional","affiliation":[{"name":"Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-0098","authenticated-orcid":false,"given":"Ji-Ming","family":"Ye","sequence":"additional","affiliation":[{"name":"Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"key":"2021113011134329900_B1","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1016\/S0140-6736(15)60264-1","article-title":"Global trends and projections for tobacco use, 1990-2025: an analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control","volume":"385","author":"Bilano","year":"2015","journal-title":"Lancet"},{"volume-title":"WHO Report on the Global Tobacco Epidemic 2017","year":"2017","author":"WHO","key":"2021113011134329900_B2"},{"key":"2021113011134329900_B3","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1093\/ije\/dyr077","article-title":"Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index","volume":"40","author":"Freathy","year":"2011","journal-title":"Int. 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