Contributors

Financial Support Received from: Utah Clinical and Translational Science Institute R25TR004388

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Presented at the Annual Biomedical Research Conference for Minoritized Scientists (ABRCMS)

Obesity, defined as excessive body fat accumulation, is a significant public health issue linked to severe health risks such as cardiovascular disease, type 2 diabetes, and cancer. According to the CDC, the prevalence of severe obesity in the U.S. nearly doubled from 4.7% to 9.2% between 2000 and 2020. This research investigates the role of primary cilia in regulating hyperplastic and hypertrophic fat expansion and examines how G protein-coupled receptors (GPCRs) influence adipogenesis.

Adipose tissue, a critical connective tissue, supports energy storage, endocrine activity, thermoregulation, and organ protection. Fat expansion occurs in two ways: hypertrophy, where existing adipocytes enlarge, often leading to inflammation and insulin resistance, and hyperplasia, where preadipocytes differentiate into new, metabolically healthier adipocytes. Using 3T3-L1 mouse embryonic fibroblasts treated with a differentiation cocktail, our lab models adipogenesis and investigates the regulatory role of insulin and cyclic AMP (cAMP) in this process.

Primary cilia, hair-like structures on the cellular membrane, act as sensors for signaling pathways involved in cell differentiation. This study focuses on how ciliary GPCRs influence fat expansion. Through a ligand screen, two key GPCRs, MCH and Kisspeptin, were identified as relevant to adipogenesis. Understanding the interaction between ciliary GPCRs and their ligands could elucidate how primary cilia regulate preadipocyte differentiation and fat expansion.

The findings of this research may pave the way for therapeutic strategies to promote healthier fat development and reduce obesity-related health risks.

Keywords

Obesity, Severe obesity, Adipose tissue, GPCRs, Adipogenesis, Fat expansion, Ciliary signaling, Insulin signaling, cAMP, MCH receptor, Kisspeptin receptor, Ligand screening, Obesity-related risks, Therapeutic strategies

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