Melanin-concentrating hormone (MCH) is a peptide that regulates appetite and energy expenditure in mammals. In adipocytes, MCH triggers production of leptin, an appetite suppressing hormone. The MCH receptor, MCHR1, desensitizes to MCH following stimulation and receptor internalization may be involved. Using a leptin promoter driven luciferase reporter, we investigated how beta-arrestin 1 and 2 effect MCH signaling. Beta-arrestin 1 and 2 are involved in clathrin mediated endocytosis. In BHK 570 cells expressing MCHR1, we observed a 1.2 fold increase in reporter activity following a six hour MCH treatment. Beta-arrestin-1 and 2 overexpression in these cells resulted in 1.1 and 1.0 fold increases respectively following MCH treatment. We also investigated effects of knocking down Caveolin-1 with RNAi in BHK cells. Caveolin-1 is involved in an independent endocytosis pathway. We observed a 1.4 fold increase in reporter activity following treatment. These results support the idea that receptor internalization contributes to MCH desensitization.
|Presenter:||Robert Carroll (Undergraduate Student)|
|Time:||9:40 am Session I|