Tuesday, February 17, 2026 2/17/2026

THE ROLE OF HEPATOKINE ORM2 IN ADIPOSE TISSUE INFLAMMATION

Award Number: R01DK126656
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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THE ROLE OF HEPATOKINE ORM2 IN ADIPOSE TISSUE INFLAMMATION - ABSTRACT Bile acids (BAs) have recently emerged as metabolic regulators in obesity and type 2 diabetes. We discovered that the BA overload in farnesoid X receptor (FXR) and small heterodimer partner (SHP) double knockout mice unexpectedly exerts anti-obesity and anti-diabetic effects. Intriguingly, liver-specific FXR/SHP ablation phenocopies the global knockout mice with striking beneficial impacts on white adipose tissue (WAT) fatty acid utilization and inflammation. This raises the possibility that hepatic BA overload confers metabolic crosstalk between the liver and adipose tissues. Our preliminary results indicate that hepatic secretion of orosomucoid 2 (ORM2) is dramatically increased by not only BA overload, but also weight-loss Roux-en Y gastric bypass (RYGB) surgery. Hepatic Orm2 overexpression greatly reduces white adipose tissue (WAT) mass, coupled with marked improvement in whole-body insulin sensitivity. Importantly, ORM2 dampens proinflammatory interferon-gamma (IFNγ) and signal transducer and activator of transcription 1 (STAT1) signaling in WAT. These exciting data support the hypothesis that the hepatokine ORM2 exerts anti-inflammatory effects in WAT, which improves insulin sensitivity. The goal of this proposal is to critically test our hypothesis by challenging mouse models of ORM2 expression with various metabolic interventions. In Aim 1, we will determine the metabolic impact of hepatic ORM2 induction on WAT function in mouse models of obesity and type 2 diabetes. Aim 2 will determine the contribution of ORM2 to the broad beneficial effects of BA overload and RYGB surgery using Orm2-deficient mice. Lastly, Aim 3 will define anti-inflammatory effects of ORM2 on CCR5-IFNγ-STAT1 axis in WAT. Our studies will identify the molecular and cellular basis of hepatokine ORM2 function on WAT inflammation, which coordinately improves metabolic phenotypes. Ultimately, we expect to provide detailed insight into BA-induced liver-adipose tissue crosstalk with direct therapeutic potential for treating obesity and type 2 diabetes.


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 = $0 )
2026	2025	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	2/15/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $390,000 )
2025	2025	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	5/1/2025	NON-COMPETING CONTINUATION	$390,000
														Subtotal = $390,000

Issue Date FY: 2024 ( Subtotal = $374,400 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	5/7/2024	NON-COMPETING CONTINUATION	$374,400
														Subtotal = $374,400

Issue Date FY: 2023 ( Subtotal = $390,000 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	4/28/2023	NON-COMPETING CONTINUATION	$390,000
														Subtotal = $390,000

Issue Date FY: 2022 ( Subtotal = $390,000 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	4/29/2022	NON-COMPETING CONTINUATION	$390,000
2022	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/18/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $390,000

Issue Date FY: 2021 ( Subtotal = $390,000 )
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	9/7/2021	NEW	-$400,000
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/28/2021	NEW	$400,000
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	9/8/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$390,000
														Subtotal = $390,000

Grand Total All Awards = $1,934,400

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THE ROLE OF HEPATOKINE ORM2 IN ADIPOSE TISSUE INFLAMMATION

Award Number: R01DK126656

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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