Project 438069

Fat cell and immune cell functions undergo parallel changes in the body during various stages of life in health and disease. The most notable examples are puberty, pregnancy, and menopause, as well as metabolic and immune diseases. Notably, both cell types display sex differences in their functions and sex steroid hormones are an integral component of this. In addition, genes and other regulatory factors (e.g. micro-RNAs) that are located on X chromosome also appear to be involved. Consequently, men and women display differences in susceptibility and resistance to metabolic and immune diseases. However, the identities of various factors/genes that mediate sex differences in fat and immune cell functions remain largely unknown. Identifying these factors and understanding how they work are crucial because of their importance in sex differences in body physiology, and their dysregulation in metabolic and immune diseases. Recently, my team has discovered that a protein called prohibitin plays important roles in sex differences in fat and immune cells. Manipulating prohibitin levels or functions in fat and immune cells simultaneously in transgenic mouse models lead to amplified sex differences in metabolic and immune diseases similar to humans, signifying its importance. However, the relative contributions of the role of prohibitin in fat cell and immune cell functions in sex-dimorphic metabolic and immune health (and the mechanisms involved) remain unknown. To delineate this, we have developed new mouse models by knocking out prohibitin in fat and immune cells. In this proposal, we will perform an in-depth study of sex differences in fat and immune cells. We anticipate that these new models, in combination with our previously developed models, will create a unique set of research tools for scientists working in this field, which will create new research opportunities, provide new research directions and stimulate research in this understudied area.