Date of Award

2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Patrick Seale

Abstract

The alarming rise in the incidence of obesity found throughout the world has precipitated a need to look for novel methods to increase energy expenditure to counter weight gain. Recently it was discovered that adult humans possess a substantial mass of brown adipose tissue (BAT), a tissue that consumes stored lipid to produce heat. Although the primary physiologic role for BAT is to protect mammals from the cold, it is currently thought that enhancing BAT mass or activating BAT in humans is a novel way to decrease adiposity. However, before BAT can be effectively utilized for therapeutic purposes a better understanding of the transcriptional regulation underlying BAT function is required. Here, we investigated the role of the transcription factor PRDM16 in BAT. We found that PRDM16 is not required for BAT development, however it is required to maintain BAT identity in adult mice. The loss of PRDM16 in adult mice led to a loss of BAT functionality and an inability to produce heat. We found that PRDM16s ability to drive a thermogenic program is due to its recruitment of Med1/the Mediator Complex to BAT-selective genes. Without PRDM16 in BAT a loss of higher order chromatin structure and a corresponding loss of transcription takes place at genes required for BAT identity and function.

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