Abstract

Obesity significantly increases the risk of metabolic problems, such as insulin resistance and type 2 diabetes. When we gain excess weight, our fat tissue can expand in two ways: hypertrophy, involving the enlargement of existing fat cells, which is associated with inflammation and insulin resistance; and hyperplasia, which generates more numerous and smaller fat cells through adipogenesis, resulting in reduced tissue inflammation and fibrosis. The mechanism by which our fat tissue expands plays a critical role in determining metabolic health. In this proposal, I aim to introduce a novel mechanism to promote healthy fat accumulation, preventing fat cell overload that triggers inflammation and insulin resistance. My focus will be on two cell types: adipose tissue macrophages (ATMs) and adipocyte precursor cells (APCs). APCs are essential for healthy fat expansion. Our research has shown that microRNA-690 (miR-690), found in anti-inflammatory ATMs, can enhance insulin sensitivity, and reduce inflammation through NAD+ metabolism. I hypothesize that with the right stimulus, macrophages can inhibit inflammation, and APCs can turn into fat cells through adipogenesis, favoring healthy fat accumulation. This research may lead to new approaches for treating obesity and its related metabolic diseases, revealing a previously unknown interaction between ATMs and APCs, guided by miR-690, to promote healthier fat tissue expansion.