Date of Award
Doctor of Philosophy
Ling Zhao, Jay Whelan, Brynn H. Voy
Recent findings of brown adipocytes and brown-like or beige adipocytes, capable of dissipating energy as heat, in adult humans have promised new hope for obesity treatment and prevention. Understanding of the regulation of brown and beige adipocytes will provide novel strategies to reach the goal. Pattern recognition receptors (PRR) are responsible for inflammation in adipose tissue, which leads to adipose dysfunction and obesity associated chronic diseases. It has been shown that PRR activation induces inflammation, leading to insulin resistance in white adipocytes and white adipose tissue (WAT). However, the roles of PRR activation in brown adipocytes and brown adipose tissue (BAT) have not been studied. In addition, in vitro and in vivo studies have shown that bioactive food components can contribute to obesity prevention; however, very few bioactive food components have been studied for their beneficial effects in promoting development and function of brown and beige adipocytes.
This dissertation reports that (1) mRNA of PRRs and inflammatory cytokines/chemokines are upregulated in the BAT of both diet induced obesity mice model and ob/ob mice model; (2) activation of PRRs induces activation of NF-κB and MAPK signaling pathways, leading to upregulation of the proinflammatory genes, MCP- 1, IL-6, RANTES, and TNF-α, in mature brown adipocytes; (3) activation of PRRs suppresses UCP-1 expression, leading to decreased mitochondrial respiration and thermogenesis in mature brown adipocytes; (4) chronic activation of PRRs reduces adipogenesis and suppresses expression of brown-specific genes in both classic brown adipocytes and multipotent stem cells. This dissertation further demonstrates that naringenin, a flavanone mainly found in citrus fruits, enhances thermogenic activation in isoproterenol-stimulated 3T3-L1 adipocytes through PKA/p38 MAPK pathways.
The results suggest that PRR-mediated inflammation in brown adipocytes may be a potential target for regulating BAT development and function for obesity treatment and prevention. Dietary bioactive compounds, such as naringenin, could be beneficial in promoting functional BAT, thereby contributing to energy expenditure.
Bae, Jiyoung, "Brown and Beige Adipocytes: Effects of Inflammation and Nutritional Intervention. " PhD diss., University of Tennessee, 2015.