Regional differences in adipose tissue development : effects of nutritional challenges on genes involved in insulin, insulin like growth factor and glucocorticoid signalling

• Main Author: Bos, Petra Marianne
• Published: University of Nottingham 2010
• Subjects: 636.085; QP Physiology
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523032

Adipose tissue development is regulated by a complex interaction between the local actions of insulin, glucocorticoids and insulin like growth factors (IGFs). A series of experiments was undertaken in which the normal development of individual adipose tissue depots and their development following periconceptional under- and overnutrition, formula feeding and juvenile obesity was investigated in sheep. Expression and abundance of glucocorticoid receptor (GR), 11β-hydroxysteroid dehydrogenases (11β-HSDs), insulin receptor, p85 subunit of phosphatidylinositol 3-kinase (p85), glucose transporter 4 (Glut4), insulin like growth factor (IGF) 1 and 2 and their receptors (IGF-R) were measured as markers of sensitivity to glucocorticoids, insulin and IGFs in individual adipose tissue depots. It was found that during early postnatal life omental adipose tissue grows faster than other depots. In all investigated groups there were marked differences in the expression of all investigated genes between adipose tissue depots. No effect was found of periconceptional nutrition on expression of the investigated genes. Weight of the mother prior to conception was negatively associated with omental GR and 11β-HSD1. Free fatty acid levels at 4 months of age were related to omental and subcutaneous 11β-HSD1 expression. Perirenal expression of IGF1R at 4 months was negatively correlated with perirenal and subcutaneous adipose tissue mass. IGF1R expression correlated with IR and GR expression. Formula feeding resulted in reduced expression of Glut4 and increased 11β-HSD1 expression. A combination of formula feeding and juvenile obesity resulted in a redistribution of adipose tissue in favour of the perirenal depot. Obesity per se resulted in a reduction of the expression of all genes and proteins examined. We have shown significant differences in markers of tissue sensitivity to the actions of insulin, glucocorticoids and insulin like growth factors between different adipose tissue depots in the body, highlighting the importance of examining those depots individually in future studies.