Biomedical Sciences ETDs

Publication Date

Spring 1-28-2025

Abstract

Abstract Adipose tissue plays a multifaceted role in regulating metabolic health and contributing to the pathophysiology of various diseases. Brown Adipose Tissue (BAT), a vital organ that senses different environmental cues such as cold stress and diet and then undergoes non-shivering thermogenesis in mammalian animals, enhancing energy expenditure to combat obesity. In our recent published study, we found that the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway exhibits doubleedge effects in regulating thermogenic function, with opposite role in BAT and white adipose tissue (WAT). To further investigate the molecular mechanisms underlying the dual role of mTORC1 in thermogenic regulation, we performed cDNA microarray to determine the effects of mTORC1 on cAMP responsive genes and observed the upregulation of Cyclin D1(CCND1) in mTORC1-inhibited BAT. Using lineage tracing model, we show that CCND1 is not only expressed in progenitor cells of BAT but also brown adipocyte. The expression of CCND1 in BAT was upregulated upon cold exposure at both levels of progenitor and adipocytes. During adipocyte differentiation, Ccnd1 gene was induced, and its protein levels display a subcellular localization shift from nuclear to cytoplasm. Activation of beta-adrenoceptor signaling did not significantly alter CCND1 expression but promoted its nuclear translocation. These results suggest that Cyclin D1 may be involved in cold-induced thermogenic activation of BAT by acting as a mediator to link potential stimuli to thermogenic adipogenesis.

Document Type

Thesis

Degree Name

Biomedical Sciences

Level of Degree

Masters

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Curt Hines

Second Committee Member

Meilian Liu

Third Committee Member

Jing Pu

Fourth Committee Member

Gen-Sheng Feng

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