# Central nervous system-adipose tissue axis in the pathogenesis of alcoholic liver disease

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $359,775

## Abstract

Abstract
Alcoholic liver disease (ALD) remains an important health problem in the United States. It ranks among
the major causes of morbidity and mortality in the world, and affects millions of patients worldwide each
year. The disease process is characterized by early steatosis, steatohepatitis, with some individuals
ultimately progressing to fibrosis/cirrhosis and liver failure. Currently, there is no accepted therapy
available to halt or reverse this process in humans. Adipose tissue dysfunction plays a critical role in the
pathogenesis of ALD; however, the exact mechanisms underlying the detrimental effect of alcohol on
adipocyte function remain elusive. In mammals, adipose tissues comprise white adipose tissue (WAT)
and brown adipose tissue (BAT), which is further categorized into “classical” BAT and “inducible” beige
fat. The adipocytes in beige fat are Ucp1-expressing thermogenic adipocytes and can be induced to
manifest the phenotypes of classical brown adipocytes via a process called “browning”. Sympathetic
nervous system (SNS) is the primary initiator of both lipolysis and browning process through releasing
norepinephrine (NE) at target adipose tissues. Physiologically, a tightly-regulated “coupling” between
lipolytic and thermogenic machinery activation must be maintained to assure that most fatty acids
released from adipose tissue by lipolysis can be ultimately utilized for thermogenesis process/heat
production. The promotive effect of chronic alcohol consumption on lipolysis activation has been well-
documented, in contrast, its effect on adipose tissue browning/thermogenic process, as well as its
potential involvement in the pathogenesis of ALD development, remain unknown. Furthermore, although
the profound effect of alcohol on central nervous system (CNS) has been widely reported, whether and
how CNS contributes to these processes remain ambiguous. The data obtained recently in my laboratory
revealed that ALD development was associated with adipose tissue cAMP/PKA pathway activation.
Nevertheless, chronic alcohol exposure inhibited adipose tissue “browning”, implying a “dissociation”
between the two physiologically coupled processes in response to increased SNS tone in response to
alcohol drinking. Based on our Preliminary Studies, we hypothesize that chronic alcohol consumption
activates SNS, however, it “dissociates” the coupling between lipolysis and browning/thermogenesis in
adipose tissues, leading to uncontrolled FFAs release and resultant fatty liver and liver damage. This
hypothesis will be tested in the following Specific Aims: AIM 1: To determine the critical role of SNS
activation in adipose tissue lipolysis and liver pathologies in response to chronic alcohol exposure; AIM
2: To determine the pathological role of impaired browning/thermogenesis process in ALD and
mechanism(s) underlying alcohol-triggered uncoupling between lipolysis and browning/thermogenesis;
and AIM 3: To elucidate the mechanism(s) underlying alcohol-...

## Key facts

- **NIH application ID:** 10240705
- **Project number:** 5R01AA026603-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** ZHENYUAN SONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $359,775
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240705

## Citation

> US National Institutes of Health, RePORTER application 10240705, Central nervous system-adipose tissue axis in the pathogenesis of alcoholic liver disease (5R01AA026603-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240705. Licensed CC0.

---

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