Illuminating the relationship between prohibitin and sex steroid hormones in adipocyte biology

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Fat 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 fat tissue). Fat cell, the structural and functional unit of fat tissue plays a key role in maintaining whole body energy and metabolic homeostasis, and sex steroid hormones have a role in both fat tissue biology and in energy homeostasis. Furthermore, sex differences are known to exist in the role of fat tissue in energy and metabolic homeostasis in the body. However, various factors that mediate such differences in fat tissue functions and consequently on the body's metabolic homeostasis are not well explored. Deciphering sex differences in fat cell biology is an important component of understanding the role of fat 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 fat cell formation. To further explore the role of prohibitin in fat tissue biology at the whole body level, my team developed a novel transgenic mouse by over-producing prohibitin in fat cells. Prohibitin transgenic mice displayed an increase in fat tissue mass in a sex-neutral manner, but they showed sex differences in their body's metabolic properties. Our data suggests that prohibitin has an important role in the maintenance of fat tissue homeostasis and point towards sex differences in its effect on fat cell function. However, the underlying mechanisms involved remain to be determined. Clearly, further investigation is required to determine the role prohibitin in fat cell biology. In this study, my HQP and I will explore the mechanisms involved in the interplay between sex steroids hormones and prohibitin which leads to sex differences in fat tissue functions and metabolic homeostasis at the systemic level. The proposed research will provide novel insights into the underlying mechanisms involved in the role of prohibitin in fat cell biology including sex differences in its effect on fat cell function. Such information is crucial to advance our understanding of the role of fat tissue in the maintenance of energy homeostasis and metabolic regulation in the body in a sex-specific manner, which is a fundamental aspect of the whole body physiology in mammals. I anticipate that at least 8-10 HQP will be trained in my program this cycle.