Grant: Discovery Grants Program - Individual

Mammals have two types of adipose (fat) tissue: brown and white, with opposing functions. White adipose tissue stores energy in the form of fat. It functions as endocrine organ that regulates glucose and lipid metabolism in the body. Brown adipose tissue, on the other hand, is a specialized form of adipose tissue found in humans, rodents and some hibernating animals. It differs from white adipose tissue in location, morphology, function, and plays a major role in energy expenditure and non-shivering thermogenesis. Thus, adipose tissues are essential and highly active metabolic and endocrine tissue that fulfil a variety of functions. The general knowledge of the key structural and functional units of both adipose tissue, the brown and white adipocytes, is well understood. However, one area that has received comparatively little attention is our understanding of the sex-specific differences in their structure and function, which are present in both humans and rodents and involves sex steroid hormones. It is also unclear whether sex-specific differences in brown and white adipose tissues are interrelated, independent from each other, or a combination of both. In the past DG, my group discovered that a protein, prohibitin-1, has a role in sex-specific differences in both types of adipose tissues, which appears to be mediated through its cell compartment (i.e., mitochondria and plasma membrane)-specific function and involves an interplay with sex steroid hormones. However, the underlying mechanisms involved remain unclear, which we aim to explore in this DG using a novel mouse model developed in-house. We hypothesize that the post-translational modification of prohibitin-1 related to its cell compartment-specific function is involved in its sex-dimorphic effect in brown and white adipose tissues. Our short-term objectives are to explore the relative contribution of cell-intrinsic and sex steroid-induced sex-specific differences in brown and white adipose tissue biology. Particularly, the role of prohibitin-1's cell-compartment-specific function in the presence and absence of respective sex steroid hormones. We will achieve this using in vivo and in vitro experimental approaches in combination with pertinent cell and molecular biology tools and techniques. This program will train around 6 HQP in essential skills for fundamental research in the NSE domain. The proposed research will provide novel insights in the underlying mechanisms involved in prohibitin-1's role in sex-specific differences in brown and white adipose tissue biology and their effect on adipose tissue function, which are largely unknown. Such information is critical to achieve the long-term objective of my research program i.e., to advance our understanding of the sex-specific role of adipose tissue in the maintenance of energy homeostasis and metabolic regulation in the body. It is anticipated that this study will open new research directions in this field.