title: Differential effects of exposure to maternal obesity or maternal weight loss during the periconceptional period in the sheep on insulin signalling molecules in skeletal muscle of the offspring at 4 months of age.
abstract: Exposure to maternal obesity before and/or throughout pregnancy may increase the risk of obesity and insulin resistance in the offspring in childhood and adult life, therefore, resulting in its transmission into subsequent generations. We have previously shown that exposure to maternal obesity around the time of conception alone resulted in increased adiposity in female lambs. Changes in the abundance of insulin signalling molecules in skeletal muscle and adipose tissue precede the development of insulin resistance and type 2 diabetes. It is not clear, however, whether exposure to maternal obesity results in insulin resistance in her offspring as a consequence of the impact of increased adiposity on skeletal muscle or as a consequence of the programming of specific changes in the abundance of insulin signalling molecules in this tissue. We have used an embryo transfer model in the sheep to investigate the effects of exposure to either maternal obesity or to weight loss in normal and obese mothers preceding and for one week after conception on the expression and abundance of insulin signalling molecules in muscle in the offspring. We found that exposure to maternal obesity resulted in lower muscle GLUT-4 and Ser 9 phospho-GSK3α and higher muscle GSK3α abundance in lambs when compared to lambs conceived in normally nourished ewes. Exposure to maternal weight loss in normal or obese mothers, however, resulted in lower muscle IRS1, PI3K, p110β, aPKCζ, Thr 642 phospho-AS160 and GLUT-4 abundance in the offspring. In conclusion, maternal obesity or weight loss around conception have each programmed specific changes on subsets of molecules in the insulin signalling, glucose transport and glycogen synthesis pathways in offspring. There is a need for a stronger evidence base to ensure that weight loss regimes in obese women seeking to become pregnant minimize the metabolic costs for the next generation.
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Nicholas
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Janna L
authors.initials: JL
authors.lastname: Morrison
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia ; Discipline of Physiology, School of Molecular and Life Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Leewen
authors.initials: L
authors.lastname: Rattanatray
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
authors.affiliation: Turretfield Research Centre, South Australian Research and Development Institute, Rosedale, South Australia, Australia.
authors.forename: Dave O
authors.initials: DO
authors.lastname: Kleemann
authors.affiliation: Turretfield Research Centre, South Australian Research and Development Institute, Rosedale, South Australia, Australia.
authors.forename: Simon K
authors.initials: SK
authors.lastname: Walker
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Severence M
authors.initials: SM
authors.lastname: MacLaughlin
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Malgorzata S
authors.initials: MS
authors.lastname: Martin-Gronert
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Isabella C
authors.initials: IC
authors.lastname: McMillen
mesh_terms: D000818:Animals; D005260:Female; D005306:Fertilization; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology; D012756:Sheep; D015398:Signal Transduction; D015431:Weight Loss
chemical_list: D007328:Insulin; D009124:Muscle Proteins