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Immunometabolic consequences of alcohol-induced mesenteric lymphatic dyshomeostasis

Award Number: F30AA030909
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Immunometabolic consequences of alcohol-induced mesenteric lymphatic dyshomeostasis - Abstract The primary purpose of this Ruth L. Kirschstein NRSA F30 application is to provide the groundwork that will prepare the applicant for an academic medical career. Much of the applicant’s career development will come from work in alcohol comorbidity-related research. Alcohol is the most abused substance in the United States with about one-quarter of the adult population partaking in heavy and/or binge drinking. Chronic alcohol consumption also disrupts glucose homeostasis and is associated with the development of insulin resistance. The immune system plays a comprehensive and understated role in adipose tissue and systemic metabolism surveilling and responding to specific metabolic signals through a set of processes termed immunometabolism. Results from our previous studies suggest that alcohol-induced mesenteric lymphatic leakage and subsequent perilymphatic adipose tissue inflammation may be a primary event in the development of systemic immunometabolic dysregulation seen in chronic alcohol use. Previously our lab has demonstrated that chronic alcohol induced lymphatic leakage, increased CD3+ and CD4+ T cells, fTregs, and IL-6 in PLAT. Our studies have also shown that chronic alcohol led to decreased insulin-stimulated glucose uptake in PLAT. We speculate that cells or molecules leaking from lymphatic vessels into PLAT stimulate fTreg expansion and lead to PLAT metabolic dysregulation. Taken together, published and preliminary data support the hypothesis that lymph contents from alcohol-treated animals disrupt PLAT immune and metabolic homeostasis through fTreg expansion. The proposed study will employ a wide variety of techniques to test the hypothesis using three specific aims: (1) Lymph from alcohol-treated animals will expand FOXP3+ fTregs in naïve PLAT explants via IL33/ST2 signaling pathway, (2) alcohol-induced fTreg expansion contributes to metabolic dysregulation in PLAT, and (3) alcohol-induced PLAT metabolic dysregulation is associated with systemic metabolic consequences. Findings from the proposed studies will provide insight on the deleterious effects of alcohol-associated lymph leakage and how its constituents impact PLAT immune cell milieu, specifically fTregs, contributing to development of PLAT IR and potentially systemic IR. With a strong mentoring team committed to developing a well-rounded physician scientist, completion of the proposed training plan will ensure that the applicant is ready to embark on a career in academic medicine.


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: 2026 ( Subtotal = $56,876 )
2026	2026	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER NEW ORLEANS	433 BOLIVAR ST RM 619	NEW ORLEANS	LA	70112	ORLEANS	USA	Alcohol Research Programs	000	4	3/25/2026	NON-COMPETING CONTINUATION	$56,300
2026	2026	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER NEW ORLEANS	433 BOLIVAR ST RM 619	NEW ORLEANS	LA	70112	ORLEANS	USA	Alcohol Research Programs	001	4	3/31/2026	NON-COMPETING CONTINUATION	$576
														Subtotal = $56,876

Issue Date FY: 2025 ( Subtotal = $44,391 )
2025	2025	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER NEW ORLEANS	433 BOLIVAR ST RM 619	NEW ORLEANS	LA	70112	ORLEANS	USA	Alcohol Research Programs	001	3	6/5/2025	NON-COMPETING CONTINUATION	$564
2025	2025	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER NEW ORLEANS	433 BOLIVAR ST RM 619	NEW ORLEANS	LA	70112	ORLEANS	USA	Alcohol Research Programs	000	3	5/7/2025	NON-COMPETING CONTINUATION	$43,827
														Subtotal = $44,391

Issue Date FY: 2024 ( Subtotal = $43,827 )
2024	2024	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER NEW ORLEANS	433 BOLIVAR ST RM 619	NEW ORLEANS	LA	70112	ORLEANS	USA	Alcohol Research Programs	000	2	2/13/2024	NON-COMPETING CONTINUATION	$42,047
2024	2024	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER NEW ORLEANS	433 BOLIVAR ST RM 619	NEW ORLEANS	LA	70112	ORLEANS	USA	Alcohol Research Programs	001	2	5/17/2024	NON-COMPETING CONTINUATION	$1,780
														Subtotal = $43,827

Issue Date FY: 2023 ( Subtotal = $39,547 )
2023	2023	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER-NEW ORLEANS	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Alcohol Research Programs	001	1	3/24/2023	NEW	$0
2023	2023	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER-NEW ORLEANS	433 BOLIVAR ST STE 815	NEW ORLEANS	LA	70112	ORLEANS	USA	Alcohol Research Programs	000	1	3/24/2023	NEW	$39,547
														Subtotal = $39,547

Grand Total All Awards = $184,641

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Immunometabolic consequences of alcohol-induced mesenteric lymphatic dyshomeostasis

Award Number: F30AA030909

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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