# Central Mechanisms Regulating Macronutrient Intake

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2022 · —

## Abstract

Obesity and diabetes are major public health issues that affect quality of life and also have high social and
economic costs. According to the CDC, approximately 10% of U.S. adults have diabetes now and 33% are
expected to have diabetes by 2050. At the same time, obesity has reached epidemic proportions, with over
60% of the U.S. population being overweight or obese. Therefore, there is a serious demand for the
development of new therapeutics to combat obesity and diabetes. Fibroblast growth factor 21 (FGF21) is an
endocrine hormone that ameliorates metabolic dysfunction in a number of obese animal models and humans.
Extended administration of FGF21 causes weight loss in rodents, and administration of FGF21 analogs to
obese humans increases weight loss and improves metabolic profiles. Recently, we discovered that FGF21
functions physiologically and pharmacologically to suppress carbohydrate intake and sweet taste preference.
Importantly, we and others have found that many of the beneficial effects of FGF21 are mediated through its
actions on the central nervous system. However, the mechanism of FGF21 action in the brain and the neuronal
target(s) for these effects has not been determined. The overall goal of this proposal is to identify the neural
circuit(s) regulating FGF21-mediated suppression of carbohydrate intake. The aims of this grant are to 1)
determine the direct neuronal target responsible for FGF21-mediated suppression of carbohydrate intake in
vivo, 2) determine the role of oxytocin signaling in FGF21’s suppressive effect on simple sugar intake, and 3)
determine the effect of FGF21 on the modulation of the mesolimbic dopamine system and feeding behavior. To
accomplish these aims, we have generated novel animal models and tools to examine these experimental
aims. These studies will provide new fundamental insights into the regulation of whole-body glucose
homeostasis and food-related reward by peripheral endocrine signals acting on the central nervous system. In
addition, these studies may identify novel therapeutic targets for the treatment of diabetes and obesity.

## Key facts

- **NIH application ID:** 10476429
- **Project number:** 5I01BX004634-04
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** Matthew Joseph Potthoff
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476429

## Citation

> US National Institutes of Health, RePORTER application 10476429, Central Mechanisms Regulating Macronutrient Intake (5I01BX004634-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10476429. Licensed CC0.

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