# Overfeeding and body weight regulation

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $45,520

## Abstract

Mammals resist large rapid changes in body weight. Studies dating back to at least the 1940’s show that
forced increases or decreases in body weight elicit neuroendocrine responses favoring restoration of previous
body mass. Despite the existence of a system that defends against weight gain, obesity has been on the rise for
more than four decades suggesting that there are factors that can attenuate or alter this system, allowing, or
even encouraging, weight gain to occur.
 This system that defends against weight gain is poorly defined due, in-part, to technical challenges
impeding study of the overfed state in model organisms. Our lab has developed a novel intragastric feeding
paradigm to induce rapid weight gain, making possible the study of the overfeeding in mice. Using this system,
mice gain 25-40% of their initial body weight in 10-14 days. Consistent with body weight being defended, once
overfeeding ceases, the mice lose weight until returning to their initial weight and adiposity. The 7-10 day return
to initial body weight is caused, in large measure, by reduced feeding. After overfeeding is stopped, animals
abstain from eating for 2-3 days and slowly increase intake until reaching their initial body weight. Characterizing
the physiology and molecular components of this graded hypophagic response, we believe, will provide insights
into regulation of body weight. This proposal focuses on one molecular component – neurons implicated in
anorexia, and one aspect of the physiology of overfeeding – the ability of palatable food to alter caloric intake.
 Calcitonin-gene related peptide (CGRP) neurons in the parabrachial nucleus (PBN) have been implicated
in anorexia and regulation of meal termination. We hypothesize that these neurons are required for overfeeding
induced anorexia to occur. Aim 1 will test whether CGRP neurons in the PBN mediate overfeeding induced
anorexia. If the hypothesis is correct, these studies will establish a neuronal pathway that defends against weight
gain and will permit future studies to identify down- and up-stream pathways. If CGRP neurons are not required
for overfeeding induced anorexia, we will have uncovered evidence for a distinct system that limits food intake.
 There is controversy about how macronutrients and palatability contribute to weight gain. Diets high in
fat and/or sucrose increase weight in many rodent strains, but it remains unclear as to whether the obesogenic
nature of these diets is due to palatability or to another, perhaps, metabolic aspect of their macronutrient content.
Our overfeeding paradigm will permit us to explore how palatability, i.e. pregastric component of eating,
modulates the defense against weight gain. Based on our preliminary data, we hypothesize that macronutrients
associated with palatable diets will attenuate the response to overfeeding through a post-ingestive mechanism.
Aim 2 will test how increased intake and weight gain on a preferred diet affect body weight defense in
...

## Key facts

- **NIH application ID:** 10049961
- **Project number:** 5F31DK122711-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Molly Rachel Gallop
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049961

## Citation

> US National Institutes of Health, RePORTER application 10049961, Overfeeding and body weight regulation (5F31DK122711-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10049961. Licensed CC0.

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