An Investigation of the Effect of Diet and Exercise on Adipose Tissue Function in Different Fat Depots

Abstract

Obesity is a leading public health challenge worldwide. Personal interventions such as diet and/or exercise management are considered effective in terms of cost and feasibility to prevent/treat obesity. To effectively implement a diet or exercise intervention, it is necessary to understand the response of different adipose tissue depots to diet and exercise. In this thesis, we investigated the effect of high fat diet (HFD) and exercise on adipose tissue function compared to chow fed mice in the different fat depots. In the chow fed controls, with aging, there was a progressive increase in systemic insulin resistance which was more pronounced with the duration of HFD (45% fats). The metabolic deterioration with HFD was accompanied by the decrease in fat cell functions (adipogenesis, mitochondrial thermogenesis, extracellular matrix (ECM) remodeling and inflammation) in different fat depots of C57BL/6 mice. In the early stages of HFD, the increased adipogenesis, ECM remodeling in subcutaneous (SAT) and epididymal (EPI) fat coupled with the maintenance of thermogenic ability in SAT (beiging of white adipocytes) and brown fat enabled them to accommodate the excess fat. However, on prolonged HFD there was a decline in metabolic function which was accompanied by infiltration of macrophages and ECM accumulation that could restrict adipose tissue expansion and led to ectopic fat deposition. Both exercise programs Endurance exercise (END) and High Intensity Interval Training (HIIT) prevented the HFD induced deterioration in metabolic health by preventing body weight gain, reducing total body fat and liver weight, and increasing lean mass. Exercise also decreased adipogenesis, inflammation, ECM accumulation and preserved thermogenesis in SAT and EPI. Investigating the effect of TGFβ1 on 3T3L1 cells showed that different responses were seen depending on the stage of adipocyte maturation. Throughout adipocyte development, TGFβ1 consistently upregulated the markers for ECM remodeling. In both early and fully differentiated adipocytes, TGFβ1 inhibited adipogenic markers and upregulated the inflammatory marker genes. There was also a difference in the thermogenic marker genes with TGFβ1 increasing them in fully differentiated adipocyte and decreasing them early in the differentiation process of adipocytes.