The role of prohibitin in adipocyte biology

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Adipose tissue is a complex, multicellular structure that profoundly influences the function of nearly all other organ systems in the body through its diverse metabolite and adipokine (cell signaling proteins secreted by adipose tissue). Adipocytes, the structural and functional unit of adipose tissue plays a key role in maintaining whole body energy homeostasis. To perform this specialized function, adipocytes rely on their mitochondria, the powerhouse of the cell. Recent evidence suggests that mitochondrial biogenesis (production of new mitochondria) is integral to adipocyte formation. However, various proteins involved in mitochondrial biogenesis during adipocyte formation are not explored. In addition, despite a critical role of mitochondria in adipocyte biology, the role of adipocyte mitochondria in adipose tissue homeostasis and on adipokine secretion are not well understood. Deciphering adipocyte biology is an important component of understanding the role of adipose tissue in energy homeostasis and metabolic regulation in the body. Under my previous Discovery Grant, my team discovered that a protein, prohibitin, has an important role in adipocyte formation. To further explore the role of prohibitin in adipose tissue biology at the whole body level, my team developed a novel transgenic mouse by over-producing prohibitin in adipocytes. Prohibitin transgenic mice displayed an increase in adipocyte mitochondrial biogenesis and adipose tissue mass in a sex-neutral manner, but sex differences in their body’s metabolic and physiological properties. Our data suggests that prohibitin has an important role in the maintenance of adipose tissue homeostasis and point towards sex differences in its effect on adipocytes function. However, the underlying mechanisms involved remain to be determined. Clearly, further investigation is required to determine the role prohibitin in adipocyte biology. In this study, my HQP and I will explore how increased level of a single protein (prohibitin) leads to a process (mitochondrial biogenesis) that requires coordination of hundred of proteins, and why their functional consequences are different in males and females. The proposed research will provide novel insights in the underlying mechanisms involved in the role of prohibitin in adipocytes biology including sex differences in its effect on adipocytes function. Such information is critical to advance our understanding of the role of adipose tissue in the maintenance of energy homeostasis and metabolic regulation in the body. I anticipate that at least 8 HQP will be trained in my program this cycle.