# Role of Adipokine FABP4 in Glucoregulation and Counter Regulatory Responses

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2020 · $504,849

## Abstract

PROJECT SUMMARY
Despite importance of counter-regulatory mechanisms to combat starvation and hypoglycemia, a significant
component of this adaptive network, adipose tissue, remains understudied. It is functionally and evolutionarily
conceivable that signals must exist to integrate this major source of energy during fasting to rest of the counter-
regulatory network. The major adipocyte fatty acid binding protein (FABP) member FABP4, is secreted from
adipocytes circulating levels rise in fasting and in the context of obesity, and the hormone acts on the liver to promote
hepatic glucose production. In this way, the high levels of circulating FABP4 that occur in obese animals appear to
have an effect reminiscent of the hyperglucagonemia that characterizes the diabetic state. The objective of this
proposal is to understand the contribution of circulating FABP4 in mediating aberrant hepatic gluconeogenesis in the
diabetic condition. Our overarching hypothesis is that FABP4 potentiates the action of glucagon signaling and is a
critical component of counter-regulatory machinery and mediator of the development of obesity-related diabetes. The
studies described in the current proposal will test this hypothesis by determining whether FABP4 is required to
mediate the effect of hyperglucagonemia in diabetes, by characterizing a potential FABP4-glucagon-glucagon receptor
(GCGR) physical interaction, and by defining the mechanism by which the FABP4 signal is propagated in hepatocytes.
These experiments will make use of genetic mouse models and biochemical and cell-based assays to dissect the
function of circulating FABP4 and its interaction with the glucagon signaling pathway. This contribution is significant
because it will illuminate the molecular signaling pathways that underlie the well-established connection between
obesity and diabetes, and may lead to the development of novel therapeutic strategies. The innovation of this work
lies in pinpointing a novel mechanism of endocrine regulation - the interaction between an adipokine and a
glucoregulatory hormone that links the adipose tissue to counter-regulatory mechanisms- and carries important
implications for metabolic disease pathogenesis.

## Key facts

- **NIH application ID:** 9866236
- **Project number:** 1R01DK123458-01
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** GOKHAN S HOTAMISLIGIL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,849
- **Award type:** 1
- **Project period:** 2019-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9866236

## Citation

> US National Institutes of Health, RePORTER application 9866236, Role of Adipokine FABP4 in Glucoregulation and Counter Regulatory Responses (1R01DK123458-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9866236. Licensed CC0.

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