title: Metabolic programming of adipose tissue structure and function in male rat offspring by prenatal undernutrition.
abstract: BACKGROUND
  A number of different pathways to obesity with different metabolic outcomes are recognised. Prenatal undernutrition in rats leads to increased fat deposition in adulthood. However, the form of obesity is metabolically distinct from obesity induced through other pathways (e.g. diet-induced obesity). Previous rat studies have shown that maternal undernutrition during pregnancy led to insulin hyper-secretion and obesity in offspring, but not to systemic insulin resistance. Increased muscle and liver glycogen stores indicated that glucose is taken up efficiently, reflecting an active physiological function of these energy storage tissues. It is increasingly recognised that adipose tissue plays a central role in the regulation of metabolism and pathophysiology of obesity development. The present study investigated the cell size and endocrine responsiveness of subcutaneous and visceral adipose tissue from prenatally undernourished rats. We aimed to identify whether these adipose tissue depots contribute to the altered energy metabolism observed in these offspring.
  
  
  METHODS
  Adipocyte size was measured in both subcutaneous (ScAT) and retroperitoneal adipose tissue (RpAT) in male prenatally ad libitum fed (AD) or prenatally undernourished (UN) rat offspring. Metabolic responses were investigated in adipose tissue explants stimulated by insulin and beta3 receptor agonists ex vivo. Expression of markers of insulin signalling was determined by Western blot analyses. Data were analysed by unpaired t-test or Two Way ANOVA followed by Fisher's PLSD post-hoc test, where appropriate.
  
  
  RESULTS
  Adipocytes in offspring of undernourished mothers were larger, even at a lower body weight, in both RpAT and ScAT. The insulin response of adipose tissue was reduced in ScAT, and statistically absent in RpAT of UN rats compared with control. This lack of RpAT insulin response was associated with reduced expression of insulin signalling pathway proteins. Adrenergic receptor-driven lipolysis was observed in both adipose depots; however insulin failed to express its anti-lipolytic effect in RpAT in both, AD and UN offspring.
  
  
  CONCLUSIONS
  Metabolic dysregulation in offspring of undernourished mothers is mediated by increased adipocyte size and reduced insulin responsiveness in both ScAT and especially in RpAT. These functional and morphological changes in adipocytes were accompanied by impaired activity of the insulin signalling cascade highlighting the important role of different adipose tissue depots in the pathogenesis of metabolic disorders.
authors.affiliation: Discipline of Physiology, School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5005 Australia.
authors.forename: Nichola
authors.initials: N
authors.lastname: Thompson
authors.affiliation: Department of Physiology, University of Veterinary Medicine, 30173 Hannover, Germany.
authors.forename: Korinna
authors.initials: K
authors.lastname: Huber
authors.affiliation: Department of Physiology, University of Veterinary Medicine, 30173 Hannover, Germany.
authors.forename: Mirijam
authors.initials: M
authors.lastname: Bedürftig
authors.affiliation: Department of Physiology, University of Veterinary Medicine, 30173 Hannover, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hansen
authors.affiliation: Institute of Physiology, Department of Medicine, University of Fribourg, 1700 Fribourg, Switzerland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Miles-Chan
authors.affiliation: Institute of Food, Nutrition and Human Health, College of Health, Massey University, Albany Campus, Auckland, 1142 New Zealand.
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Breier
keywords: Beta-adrenergic response; Insulin response; Prenatal undernutrition; Retroperitoneal adipose tissue; Subcutaneous adipose tissue