Monday, October 13, 2025 10/13/2025

Exploring Margaric Acid Role in Alcohol-Associated Liver Diseases

Award Number: R21AA032615
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/23/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Exploring Margaric Acid Role in Alcohol-Associated Liver Diseases - Alcohol-associated liver diseases (AALD) account for over 5% of global health problems, and alcohol abuse is a causal factor in more than 200 diseases. Endotoxemia and systemic inflammation are common conditions associated with morbidity and mortality in various AALD. Extensive clinical and experimental evidence indicates that disruption of intestinal epithelial tight junction and mucosal barrier dysfunction are prerequisite steps in alcoholic endotoxemia, systemic inflammation, and AALD. Therefore, the gut is a crucial target for developing therapeutics for AALD. A critical barrier in this field is that the mechanism underlying alcohol-induced TJ disruption is poorly defined. Our long-term goal is to describe the pathophysiology of AALD and develop novel therapeutic strategies by targeting gut barrier dysfunction. Our preliminary studies show that: 1) margaric acid levels in the plasma from patients with severe alcoholic hepatitis were significantly low compared to healthy subjects. 2) The plasma level of heptadecenoic acid (C17:1), the unsaturation metabolite of margaric acid, was increased in patients with severe alcoholic hepatitis. 3) Pretreatment of Caco-2 cell monolayers (an established model of the intestinal epithelium) with margaric acid-reduced ethanol (EtOH) and acetaldehyde (MeCHO)- induced TJ disruption and epithelial barrier dysfunction. 4) Margaric acid elevated Caco-2 cell rigidity (analyzed by atomic force microscopy) and attenuated EtOH and MeCHO-induced reduction of cell rigidity. These findings form the scientific premise and support the central hypothesis that margaric acid supplementation attenuates alcohol-induced gut and liver injury. We will test this hypothesis by determining that 1) Margaric acid dose- dependently attenuates alcohol-induced remodeling of the actin cytoskeleton in the intestinal epithelium, 2) Margaric acid prevents alcohol-induced disruption of TJ and AJ in the intestinal epithelium, 3) Margaric acid supplementation of the diet attenuates alcohol-induced gut and liver injury in a dose-dependent manner, and 4) Margaric acid (C17:0) to heptadecenoic acid (C17:1) ratio drives alcohol-induced gut and liver injury. The expected outcome of these studies will help establish the therapeutic potential of margaric acid in treating alcohol-associated diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $404,250 )
2025	2025	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Alcohol Research Programs	000	1	9/23/2025	NEW	$404,250
														Subtotal = $404,250

Grand Total All Awards = $404,250

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Exploring Margaric Acid Role in Alcohol-Associated Liver Diseases

Award Number: R21AA032615

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/23/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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