Thursday, November 21, 2024 11/21/2024

Role of chive-derived exosome-like nanoparticles in suppressing inflammation in obesity

Award Number: R01DK124590
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Obesity is a chronic progressive disease that leads to the development of heart disease, stroke, and type 2 diabetes, which are among the top ten leading causes of death in the United States. The initiation and progression of obesity-related diseases is strongly associated with chronic low-grade inflammation, and the NLRP3 inflammasome is a key sensor that instigates inflammation in obesity. Targeting NLRP3 inflammasome-mediated inflammation should curb or prevent the disease progression and thus holds therapeutic promise to combat obesity-related diseases. However, effective and safe strategies that specifically inhibit the NLRP3 inflammasome in obesity have not been developed for patient treatment. As such, the long- term goal of our research is to develop a new dietary strategy or therapeutic modality to suppress NLRP3 inflammasome activity and inflammation in obesity and obesity-related diseases. As an initial step, this project will define the role of chive-derived exosome-like nanoparticles (C-ELNs) in suppressing inflammation in obesity. Our pilot studies found that C-ELNs strongly inhibited NLRP3 inflammasome activation in primary macrophages. One of their bioactive molecules, 1,2-dilinoleoyl-sn-glcyero-3-phosphocholine, was identified as an inhibitor of the NLRP3 inflammasome. Oral administration of C-ELNs, started concomitantly with high-fat diet feeding, reduced NLRP3 inflammasome activity and improved metabolic health in the C57BL/6J mice. Building on our preliminary work, this project will test the central hypothesis that C-ELNs contain active biomolecules that inhibit NLRP3 inflammasome activity and ameliorate inflammation in obesity. This hypothesis will be tested through two specific aims: 1) identify active biomolecules in C-ELNs that inhibit NLRP3 inflammasome activity and 2) define the role of C-ELNs and their active biomolecules in suppressing inflammation in obesity. Successful completion of the proposed research be the first step toward the translation of C-ELNs and active biomolecules into an intervention to suppress NLRP3 inflammasome activity and inflammation in obesity. Utilizing dietary ELNs to target the NLRP3 inflammasome is an innovative approach. The unique features of dietary ELNs, including tissue bioavailability, bioactivity, and biomolecule protection and delivery, as well as their abundance in edible plants confer upon them high translational potential.


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: 2024 ( Subtotal = $315,810 )
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST # 830861	LINCOLN	NE	68503	LANCASTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	3	8/27/2024	NON-COMPETING CONTINUATION	-$1
2024	2024	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	005	4	8/27/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
2024	2024	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	4	8/22/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$315,809
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST # 830861	LINCOLN	NE	68503	LANCASTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	8/20/2024	NON-COMPETING CONTINUATION	-$315,497
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST	LINCOLN	NE	68503	LANCASTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/6/2024	NON-COMPETING CONTINUATION	$19,719
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST	LINCOLN	NE	68503	LANCASTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/29/2024	NON-COMPETING CONTINUATION	$295,779
														Subtotal = $315,810

Issue Date FY: 2023 ( Subtotal = $335,661 )
2023	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/19/2023	NON-COMPETING CONTINUATION	$335,661
														Subtotal = $335,661

Issue Date FY: 2022 ( Subtotal = $348,975 )
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/20/2022	NEW	$348,975
														Subtotal = $348,975

Grand Total All Awards = $1,000,446

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Role of chive-derived exosome-like nanoparticles in suppressing inflammation in obesity

Award Number: R01DK124590

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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