Contributors
Financial Support From: Utah Clinical and Translational Science Institute
Preview
Description
According to the CDC, the percentage of Americans with severe obesity nearly doubled from 4.7% to 9.2% between 2000 and 2020. Obesity, characterized by excessive body fat accumulation, poses significant health risks including cardiovascular disease, type 2 diabetes, and cancer. My lab’s research aims to determine how primary cilia influence hyperplastic and hypertrophic fat expansion and to understand the mechanisms through which GPCRs (G protein-coupled receptors) modify adipogenesis. Adipose tissue, or fat tissue, is a connective tissue crucial for energy storage, endocrine activity, thermoregulation, and organ protection. We focus on preadipocytes, the precursors to mature fat cells. Hypertrophic fat expansion, associated with higher inflammation and insulin resistance, occurs when existing adipocytes increase in size. In contrast, hyperplastic fat expansion, which is metabolically healthier, involves the differentiation of preadipocytes into new adipocytes. In our lab, we mimic adipogenesis by treating 3T3-L1 mouse embryonic fibroblasts with a differentiation cocktail, inducing them to become mature adipocytes. This process is regulated by signals such as insulin and cyclic AMP (cAMP). Primary cilia are hair-like structures on the cellular membrane that act as sensors in signaling pathways regulating cell differentiation. My study focuses on how primary cilia, through ciliary GPCRs, affect fat expansion. GPCRs respond to external signals by activating intracellular pathways via ligands (molecules that bind to receptors to induce a response). Through a ligand screen, I identified two GPCRs (MCH and Kisspeptin) that are relevant to this process. Understanding the interaction between ciliary GPCRs and their ligands is crucial, as it may reveal how primary cilia regulate adipogenesis and fat expansion. This research aims to elucidate the molecular role of primary cilia in preadipocyte differentiation, potentially leading to therapeutic strategies for healthier adipocyte production and reducing obesity-related health risks.
Keywords
Obesity, Severe obesity trends, Adipose tissue, Primary cilia, GPCRs (G protein-coupled receptors), Adipogenesis, Preadipocytes, Fat expansion, Hypertrophic fat expansion, Hyperplastic fat expansion, 3T3-L1 mouse embryonic fibroblasts, Ciliary signaling pathways, Insulin signaling, Cyclic AMP (cAMP), MCH receptor, Kisspeptin receptor, Ligand screening, Cellular differentiation, Obesity-related health risks, Therapeutic strategies for obesity