# Adiponectin signaling and macrophage function

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $499,391

## Abstract

Abstract
Abdominal obesity is tightly associated with a chronic low-grade inflammation that predisposes to insulin
resistance and the development of type 2 diabetes. Visceral adipose tissues, especially mesenteric adipose
tissue, exhibit depot-specific immune and metabolic differences compared with subcutaneous adipose tissue
and has been linked to varying degrees of metabolic diseases. Adiponectin is an adipokine that possesses anti-
diet-induced inflammation and insulin resistance functions. While the beneficial role of adiponectin is largely
explored in subcutaneous adipose tissue, the role of adiponectin in controlling peritoneal cavity organ
inflammation and mesenteric adipose tissue expansion remains largely unclear. The proposed study aims at
elucidating the role of adiponectin signaling in regulating macrophage function and metabolic homeostasis,
focusing on a new target of the adiponectin signaling pathway, the abhydrolase domain containing 17B
depalmitoylase (ABHD17B). The premise of the current study is based on several key findings made in our
preliminary studies: 1) the Abhd17b gene is selectively expressed in macrophage; its expression is greatly
reduced in adiponectinKO mice or high fat diet-fed mice; 2) Abhd17b deficiency exacerbates diet-induced
abdominal obesity, visceral organ inflammation, insulin resistance, and mesenteric adipose tissue expansion; 3)
Abhd17b deficient macrophage displayed impaired phagocytic ability and augmented inflammation. These data
suggest the role of ABHD17B in mediating the anti-inflammatory function of adiponectin in macrophage. Our
overarching hypothesis is that ABHD17B downregulation-induced macrophage dysfunction may be a key
mechanism underlying adiponectin deficiency-induced metabolic impairment in obesity. The studies described
in this proposal will test this hypothesis by characterizing the physiological roles of ABHD17B in mediating
adiponectin function and by characterizing the mechanism by which ABHD17B mediates the beneficial effects
of adiponectin on phagocytosis and anti-inflammation. Our multidisciplinary team of scientists will use genetic
mouse models and biochemical and cell-based assays to dissect the function and mechanism of ABHD17B in
regulating adiponectin signaling. Given the vast impact of abdominal obesity on human health, this proposed
work offers a unique and innovative approach to interrogate the functional roles and regulation of a new target
of adiponectin, ABHD17B, in mediating the anti-inflammation and anti-insulin resistant roles of adiponectin. The
mechanistical studies will help to develop new therapeutic treatment of abdominal obesity related metabolic
diseases including type 2 diabetes.

## Key facts

- **NIH application ID:** 10911331
- **Project number:** 5R01DK134637-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Lily Q Dong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $499,391
- **Award type:** 5
- **Project period:** 2023-08-22 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911331

## Citation

> US National Institutes of Health, RePORTER application 10911331, Adiponectin signaling and macrophage function (5R01DK134637-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10911331. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*