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Role of FGF21 Action in Hypothalamic Neurons in Obesity-Associated Hypertension

Award Number: R01HL162773
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Role of FGF21 Action in Hypothalamic Neurons in Obesity-Associated Hypertension - Project Summary / Abstract Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Obesity which has become common in the US and throughout the world is a major cause of hypertension, but the mechanisms underlying the relationship between obesity and hypertension remain largely unknown. The goal of this proposal is to identify the neuronal and molecular processes that control blood pressure and how dysregulation in these processes contribute to obesity-associated cardiovascular risks. This proposal is based on the hypothesis that obesity-induced elevation in the hormone fibroblast growth factor 21 (FGF21) promotes hypertension by activating ventromedial hypothalamic neurons expressing steroidogenic factor 1 (SF1) to increase sympathetic nerve activity. We will use a multidisciplinary strategy combining cutting edge neuro- technologies to precisely and remotely modulate or monitor the activity of SF1 neurons in freely moving animals with unique genetically engineered mouse models that permit selective modulation of FGF21 signaling in SF1 neurons and sophisticated integrative physiology for sympathetic and cardiovascular phenotyping. We plan to test our central hypothesis by determining how chemogenetic- or optogenetic-mediated activation or inhibition of SF1 neuron activity affects sympathetic outflow and arterial pressure under normal conditions as well as in obesity. We will also explore the contribution of FGF21 signaling in ventromedial hypothalamus including SF1 neurons to sympathetic and arterial pressure control and obesity-associated hypertension and sympathetic nerve activation. This work should unravel novel mechanisms that underlie obesity-associated sympathetic activation and hypertension, making our work of high clinical relevance. Insights into the cellular and molecular processes that control the sympathetic tone that regulates cardiovascular function may make it possible to selectively interfere with the damage obesity inflicts on cardiovascular sympathetic functions.


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 = $585,994 )
2026	2026	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	4	2/16/2026	NON-COMPETING CONTINUATION	$568,055
2026	2026	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	001	4	4/23/2026	NON-COMPETING CONTINUATION	$17,939
														Subtotal = $585,994

Issue Date FY: 2025 ( Subtotal = $597,952 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	001	3	8/4/2025	NON-COMPETING CONTINUATION	$59,796
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	3	11/20/2024	NON-COMPETING CONTINUATION	$538,156
														Subtotal = $597,952

Issue Date FY: 2024 ( Subtotal = $585,994 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	001	2	6/26/2024	NON-COMPETING CONTINUATION	$47,838
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	2	11/22/2023	NON-COMPETING CONTINUATION	$538,156
														Subtotal = $585,994

Issue Date FY: 2023 ( Subtotal = $597,952 )
2023	2023	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	1	12/12/2022	NEW	$597,952
														Subtotal = $597,952

Grand Total All Awards = $2,367,892

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Role of FGF21 Action in Hypothalamic Neurons in Obesity-Associated Hypertension

Award Number: R01HL162773

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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