title: The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats.
abstract: Early-life stress affects metabolic outcomes and choice of diet influences the development of metabolic disease. Here we tested the hypothesis that chronic sugar intake exacerbates metabolic deficits induced by early-life stress. Early-life stress was induced in Sprague-Dawley rats using limited nesting material in early lactation (LN, postnatal days 2-9), and siblings were given chow alone or with additional sucrose post weaning (n = 9-17 per group). Female control and LN siblings had unlimited access to either chow plus water, or chow and water plus 25% sucrose solution (Sucrose), from 3-15 weeks of age. Weekly body weight and food intake were measured. Glucose and insulin tolerance were tested at 13 and 14 weeks of age, respectively. Rats were killed at 15 weeks. Hepatic triglyceride and markers of lipid synthesis - fatty acid synthase, acetyl-CoA carboxylase alpha and oxidation - and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) were examined. Mediators of hepatic glucocorticoid metabolism, specifically 11-beta hydroxysteroid dehydrogenase-1 (11βHSD-1), 5-α reductase, and glucocorticoid and mineralocorticoid receptor mRNAs were also measured. Sucrose increased caloric intake in both groups, but overall energy intake was not altered by LN exposure. LN exposure had no further impact on sucrose-induced glucose intolerance and increased plasma and liver triglycerides. Hepatic markers of fat synthesis and oxidation were concomitantly activated and 11βHSD-1 mRNA expression was increased by 53% in LN-Sucrose versus Con-Sucrose rats. Adiposity was increased by 26% in LN-Sucrose versus Con-Sucrose rats. Thus, LN exposure had minimal adverse metabolic effects despite high-sugar diet postweaning.
authors.affiliation: a Department of Pharmacology , School of Medical Sciences , UNSW Australia, UNSW Sydney , New South Wales , Australia.
authors.forename: Jayanthi
authors.initials: J
authors.lastname: Maniam
authors.affiliation: a Department of Pharmacology , School of Medical Sciences , UNSW Australia, UNSW Sydney , New South Wales , Australia.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Antoniadis
authors.affiliation: a Department of Pharmacology , School of Medical Sciences , UNSW Australia, UNSW Sydney , New South Wales , Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000187:drug effects / Q000235:genetics; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000187:drug effects / Q000235:genetics; D000103:Acetyl-CoA Carboxylase; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D004032:Diet; D019422:Dietary Sucrose / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects / Q000523:psychology*; D002149:Energy Intake / Q000187:drug effects; D054890:Fatty Acid Synthase, Type I / Q000187:drug effects / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects / Q000523:psychology; D005260:Female; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000235:genetics; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D019422:Dietary Sucrose; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D014157:Transcription Factors; D014280:Triglycerides; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D054890:Fatty Acid Synthase, Type I; D000103:Acetyl-CoA Carboxylase
keywords: 11-Beta hydroxysteroid dehydrogenase 1; early-life stress; glucose/insulin tolerance; hepatic triglyceride; limited nesting; sucrose