title: Maternal cigarette smoke exposure contributes to glucose intolerance and decreased brain insulin action in mice offspring independent of maternal diet.
abstract: BACKGROUND
  Maternal smoking leads to intrauterine undernutrition and is associated with low birthweight and higher risk of offspring obesity. Intrauterine smoke exposure (SE) may alter neuroendocrine mediators regulating energy homeostasis as chemicals in cigarette smoke can reach the fetus. Maternal high-fat diet (HFD) consumption causes fetal overnutrition; however, combined effects of HFD and SE are unknown. Thus we investigated the impact of combined maternal HFD and SE on adiposity and energy metabolism in offspring.
  
  
  METHODS
  Female Balb/c mice had SE (2 cigarettes/day, 5 days/week) or were sham exposed for 5 weeks before mating. Half of each group was fed HFD (33% fat) versus chow as control. The same treatment continued throughout gestation and lactation. Female offspring were fed chow after weaning and sacrificed at 12 weeks.
  
  
  RESULTS
  Birthweights were similar across maternal groups. Faster growth was evident in pups from SE and/or HFD dams before weaning. At 12 weeks, offspring from HFD-fed dams were significantly heavier than those from chow-fed dams (chow-sham 17.6±0.3 g; chow-SE 17.8±0.2 g; HFD-sham 18.7±0.3 g; HFD-SE 18.8±0.4 g, P<0.05 maternal diet effect); fat mass was significantly greater in offspring from chow+SE, HFD+SE and HFD+sham dams. Both maternal HFD and SE affected brain lactate transport. Glucose intolerance and impaired brain response to insulin were observed in SE offspring, and this was aggravated by maternal HFD consumption.
  
  
  CONCLUSIONS
  While maternal HFD led to increased body weight in offspring, maternal SE independently programmed adverse health outcomes in offspring. A smoke free environment and healthy diet during pregnancy is desirable to optimize offspring health.
authors.affiliation: School of Medical and Molecular Bioscience, Faculty of Science, University of Technology, Sydney, Sydney, New South Wales, Australia. hui.chen-1@uts.edu.au
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Iglesias
authors.forename: Vanni
authors.initials: V
authors.lastname: Caruso
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D050154:Adiposity; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D018149:Glucose Intolerance / Q000139:chemically induced*; D007328:Insulin / Q000378:metabolism*; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D018811:Maternal Exposure; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008807:Mice, Inbred BALB C; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha; D000217:Acyltransferases
chemical_list: D002334:Carnitine O-Palmitoyltransferase; D007328:Insulin; D020738:Leptin; D008049:Lipase; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C498648:Slc16a4 protein, mouse; C490426:Slc16a7 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
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