Delineating the impact of beige adipocytes in the metabolism

About This Grant

Project Summary In this proposal, we address a critical gap in our understanding of adipose tissue biology and energy metabolism, with a focus on the role of beige adipocytes in whole-body energy expenditure. Despite extensive research linking the beiging of subcutaneous white adipose tissue (scWAT) to increased energy expenditure and improved metabolic health, direct evidence for the contribution of beige adipocytes to whole-body metabolism remains elusive. This knowledge gap persists due to the lack of tools for selectively targeting beige adipocytes in vivo. Our preliminary data, using a novel scWAT-specific UCP1 knockout mouse model, challenge the prevailing dogma by demonstrating that UCP1 in scWAT is not required for beiging-induced tissue-specific or whole-body energy expenditure. This unexpected finding raises critical questions about the mechanisms underlying the metabolic benefits of browning. We propose to elucidate these mechanisms using innovative genetic tools and two specific aims. In Aim 1, we will determine the role of scWAT beiging in metabolic health. In Aim 2, we will investigate the impact of the creatine cycle in beige adipocytes on whole-body metabolism. This research will provide insights into the hierarchical importance of various beiging-induced adaptations and their contributions to metabolic health, advance our understanding of adipose tissue biology, and provide new insights into the development of and the metabolic pathways controlling energy consumption in beige adipocytes. Ultimately, this basic science work aims to identify new targets and strategies for the treatment and prevention of obesity in the future.