RUI: Adaptation of MCH Receptor Function During Differentiation of Adipocytes

Suny College At Brockport, Brockport NY

Investigators

Abstract

The control of hormone signaling before, during, and after cell maturation requires an intricate program of coordinated activities. During growth and development, tissues undergo expansion and specialization to adapt to the physiological needs of the animal. Variations in cell-to-cell responsiveness within a tissue depends on the portfolio of proteins available for signaling cellular change. Cell sub-compartments, or microenvironments, may enhance or desensitize signals according to environmental cues. This project tests the hypothesis that melanin-concentrating hormone, or MCH, signals changes as a fat cell matures, and that MCH also participates in the fat cell maturation process. Results will enhance our understanding of the interplay between appetite signaling and fat storage. Hands-on student learning is emphasized through independent research experiences, and by providing an interdisciplinary framework that engages undergraduate and Masters students in the scientific method and technological advances in receptor biology, within the context of human obesity. Basic research on the development of adipose tissue is relevant to biology, medicine and food science. To gain a more complete understanding of how cells respond to G protein-coupled receptor (GPCR)-derived signals, the role of membrane microenvironments must be considered; that individual sub-populations of proteins may vary across different regions of the cell, and that differentiation alters those microenvironments. The differentiating 3T3-L1 adipocytes and the GPCR signaling pathway were chosen as a signaling microenvironment. It is targeted by melanin-concentrating hormone (MCH), which signals appetite in many mammals. This project specifically addresses the following Aims to increase understanding of the function of the MCH receptor (MCHR)1 in different cellular contexts: 1) Determine the importance of MCHR1 localization to primary cilia in differentiating pre-adipocytes; 2) Analyze MCHR1 signals that could promote expansion and proliferation in of adipose tissue; and 3) Analyze localization and trafficking of MCHR1 in 3T3-L1 cells in different states of cellular differentiation. Biochemical isolation methods, RNA Seq, mass spectrometry, immunodetection and confocal microscopy will be used to accomplish these aims. Experiments are designed to enable the participation and success of undergraduate and Master's research students.