Increased adipose tissue hypoxia and capacity for angiogenesis and inflammation in young diet-sensitive C57 mice compared to diet-resistant FVB mice

OBJECTIVE: High-fat diets result in increased body weight. However, this is not uniform and determining the factors that make some animals or individual more susceptible to this diet-induced weight gain is a critical research question. The expansion of white adipose tissue (WAT) associated with weight gain requires high rates of angiogenesis to support the expanding tissue mass. We hypothesized that diet-induced obese (DIO) mice have a greater capacity for WAT angiogenesis and remodeling than diet-resistant (DR) mice at a young age, prior to age or diet-induced obesity. DESIGN: We measured body weight and body composition by NMR. We compared the expression of genes related to lipid metabolism, angiogenesis and inflammation by RT-qPCR and PCR arrays. WAT morphology and distribution of adipocyte size were analyzed. The level of hypoxia and vascular density was assessed by immunohistochemistry in WAT of young mice. RESULTS: C57Bl/6 mice were DIO and FVB/N mice DR after 8 weeks on a low fat diet or high fat diet (HFD). However, C57Bl/6 mice had lower body weight, lower adiposity, smaller adipocytes and decreased leptin and lipogenic genes expression in AT than FVB/N mice at 9 weeks of age on a chow diet. Despite having smaller adipocytes, the level of hypoxia and the expression of pro-angiogenesis genes were higher in WAT of young C57Bl/6 mice than young FVB/N mice. In addition, expression of genes related to macrophages and their recruitment, and to proinflammatory cytokines, was significantly higher in WAT of young C57Bl/6 mice than young FVB/N mice. CONCLUSION: These data suggest that the potential for WAT remodeling in early period of growth is higher in C57Bl/6 mice as compared to FVB/N mice and we hypothesize that it may contribute to the increased susceptibility to DIO of C57Bl/6 mice.