To Örebro University

The increasing prevalence of obesity and related disorders in later life are associated with the early life nutritional environment. Both the intrauterine growth restriction (IUGR) due to low nutrition or enhanced growth by over-nutrition can predispose for obesity, inflammation, type 2 diabetes mellitus (T2D) and metabolic syndromes. A chronic low grade inflammation of adipose tissue is considered as an important component of insulin resistance and T2D. We investigated the effects of late gestational under (LOW) and over-nutrition (HIGH) combined with early postnatal high carbohydrate high fat (HCHF) diet on inflammatory responses of adipose tissue of young lambs. In short, twin bearing multiparous Texel ewes were exposed to either LOW or HIGH or normal (NORM) diets during last six weeks of gestation. Moreover, twin lambs from those ewes were provided one with HCHF diet and another with conventional sheep diet (CONV) from three days to six months of age. Through gene expression profiling and glucose-insulin functional analysis, we found that young lambs had developed a significant level of adipose tissue inflammation and had reduced glucose and insulin sensitivity. We found that both kinds of prenatal malnutrition showed less significant effects except in perirenal adipose tissue where a marked overexpression of monocyte chemoattractant protein-1(MCP-1) and interleukin-6 (IL-6) was observed. On the other hand, postnatal HCHF diet was found to be the main contributing factor for adipose tissue inflammation as it caused the overexpression of most of the proinflammatory genes studied irrespective of adipose tissue depots. Additionally, when the prenatal malnutritions were combined with postnatal HCHF diet, they induced an upregulation of MCP-1 in perirenal fat and TLR4 in mesenteric fat. Therefore, we suggest that postnatal HCHF diet and its interaction with prenatal diets induce early adverse effects on adipose tissue function and metabolism.

Key words: proinflammatory genes, foetal programming, macrophages