The impact of diet in early life on adipose tissue growth and development in sheep

Abstract

Adipose tissue is found in two main forms: white (WAT), which stores energy; and brown (BAT), which dissipates energy as heat by means of a unique mitochondrial protein, UCP1. In large mammals, BAT is rapidly replaced by WAT after birth, but it has recently been found that functional BAT is present in human adults, which raises the possibility that it could be manipulated to burn off excess fat. The main aim of this thesis was to investigate, using sheep as a model, the effect of early nutritional interventions on fat mass and on the expression in adipose tissue of genes involved in adipogenesis, metabolism, thermogenesis and development. A secondary aim was to study their ontogeny in sternal adipose tissue. Study A examined the effect of fat supplements given to lactating ewes on the sternal adipose tissue of their offspring. Ewes were allocated to one of three feeding groups, one control and two supplemented (sunflower or canola oil), for 28 days after parturition, and their lambs were sampled at 7 and 28 days of age. Study B investigated the effect of late gestational and postnatal diet on the sternal and subcutaneous adipose tissue of 6 month-old lambs. Twin-pregnant ewes were divided into three dietary groups for the last 6 weeks of gestation: undernourished, control or overnourished. One lamb from each twin pair was fed a control diet, and the other a high-carbohydrate, high-fat (HCHF) diet. In the first month after birth, changes in gene expression in sternal adipose tissue were comparable to those previously described in perirenal adipose tissue, with the expression of most thermogenic genes declining to almost undetectable levels by 28 days of age. There was a disparity in the expression profiles of the two principal regulators of adipogenesis, PPARγ and C/EBPα, with expression of the former increasing with age, and that of the latter peaking at 7 days of age. A sunflower, but not canola, oil supplement fed to lactating ewes increased the relative adipose tissue weight of female, but not male, lambs at 28 days of age. Both supplements increased the plasma concentration of leptin at 7 and 28 days of age in females, but not males. Supplementation had a greater effect on gene expression at 7 than at 28 days of age, but no overall pattern emerged. Maternal undernutrition reduced birth weight in males, but not females, although body weight was unaffected by 6 months of age. A postnatal HCHF diet increased fat mass in all adipose tissue depots tested, and reduced expression of most adipogenic and metabolic genes in sternal and subcutaneous adipose tissue by around 50 %. Expression of thermogenic genes was barely detectable in either tissue at 6 months of age. In conclusion, expression of thermogenic genes in sternal adipose tissue declines with age, a response that is unaffected by maternal fat supplementation during lactation or a sustained postnatal HCHF diet