Mapping the Novel VMH-R-spondin 1 Neural Circuit – UROP Spring Symposium 2024

Mapping the Novel VMH-R-spondin 1 Neural Circuit

Elisabeth Lawson

Pronouns: She/Her

Research Mentor(s): Alison Affinati
Research Mentor School/College/Department: Internal Medicine / Medicine
Program:
Authors: Elisabeth Lawson, Patrick Robichaud, Alison Affinati
Session: Session 1: 9:00 am – 9:50 am
Poster: 3

Abstract

When food is ingested, the body naturally increases energy expenditure to maintain energy and metabolic homeostasis through several mechanisms including producing heat through brown adipose tissue (BAT) thermogenesis. However, prolonged high-fat diet (HFD) intake results in a poorly understood inappropriate decrease of energy expenditure by decreasing BAT thermogenesis despite the higher caloric content of the food. R-spondin-1 (Rspo1) is a secreted protein present in neurons of the ventromedial nucleus of the hypothalamus (VMH) that is expressed in response to metabolic stimuli. Previous studies show a likely relationship between Rspo1-expressing VMH neurons and BAT thermogenesis, yet the precise mechanisms and pathways behind this relationship are largely unexplored. This project aims to observe the behavior of Rspo1 expression in the brain through fluorescent immunohistochemistry when insulin is injected into the third ventricle via intracerebroventricular (ICV) administration. We expect that Rspo1-expressing neurons will be activated and will project to Agouti-related peptide (AgRP) or Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC). This will be determined by using the retrograde tracing property of the rabies virus. The ultimate goal is to map the VMH-R-spondin 1 neural circuit that regulates BAT thermogenesis and determine whether the altered function of Rspo1 neurons of the VMH in response to HFD plays a key role in energy imbalance induced by HFD. This study will aid future studies that will determine how HFD disrupts energy homeostasis and will assist in the progress of developing brain-based treatments for metabolic diseases.

Biomedical Sciences, Interdisciplinary, Natural/Life Sciences

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