title: Low birth weight is associated with adiposity, impaired skeletal muscle energetics and weight loss resistance in mice.
abstract: BACKGROUND
  In utero undernutrition is associated with obesity and insulin resistance, although its effects on skeletal muscle remain poorly defined. Therefore, in the current study we explored the effects of in utero food restriction on muscle energy metabolism in mice.
  
  
  METHODS
  We used an experimental mouse model system of maternal undernutrition during late pregnancy to examine offspring from undernourished dams (U) and control offspring from ad libitum-fed dams (C). Weight loss of 10-week-old offspring on a 4-week 40% calorie-restricted diet was also followed. Experimental approaches included bioenergetic analyses in isolated mitochondria, intact (permeabilized) muscle and at the whole body level.
  
  
  RESULTS
  U have increased adiposity and decreased glucose tolerance compared to C. Strikingly, when U are put on a 40% calorie-restricted diet they lose half as much weight as calorie-restricted controls. Mitochondria from muscle overall from U had decreased coupled (state 3) and uncoupled (state 4) respiration and increased maximal respiration compared to C. Mitochondrial yield was lower in U than C. In permeabilized fiber preparations from mixed fiber-type muscle, U had decreased mitochondrial content and decreased adenylate-free leak respiration, fatty acid oxidative capacity and state 3 respiratory capacity through complex I. Fiber maximal oxidative phosphorylation capacity did not differ between U and C but was decreased with calorie restriction.
  
  
  CONCLUSIONS
  Our results reveal that in utero undernutrition alters metabolic physiology through a profound effect on skeletal muscle energetics and blunts response to a hypocaloric diet in adulthood. We propose that mitochondrial dysfunction links undernutrition in utero with metabolic disease in adulthood.
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Beauchamp
authors.affiliation: Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: M W
authors.initials: MW
authors.lastname: Dysart
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: G N
authors.initials: GN
authors.lastname: Kanaan
authors.affiliation: 1] Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada [2] Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Chu
authors.affiliation: 1] Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada [2] Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Blais
authors.affiliation: Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Rajamanickam
authors.affiliation: Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: E C
authors.initials: EC
authors.lastname: Tsai
authors.affiliation: Division of Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA, USA.
authors.forename: M-E
authors.initials: ME
authors.lastname: Patti
authors.affiliation: 1] Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada [2] Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: M-E
authors.initials: ME
authors.lastname: Harper
mesh_terms: D000818:Animals; D051379:Mice; D050154:Adiposity; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction / Q000009:adverse effects; D004195:Disease Models, Animal; D044342:Malnutrition / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D015431:Weight Loss; D000831:Animals, Newborn; D001724:Birth Weight
chemical_list: D001786:Blood Glucose
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