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Body weight control by hypothalamic OGT

Award Number: R01DK137467
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: 08/25/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Body weight control by hypothalamic OGT - Project Summary/Abstract The central nervous system plays a pivotal role in metabolism, within which the ventromedial hypothalamus (VMH) is crucial for proper regulation of body weight and blood glucose level. The VMH senses nutrients and circulating hormones and integrates its metabolic information to coordinate effector responses to maintain organismal homeostasis. O-linked beta-D-N-acetylglucosamine (O-GlcNAc) modification, catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. Our recent studies reveal that OGT in the VMH is required for promoting adipose tissue lipolysis and maintaining energy balance by regulating the VMH neuronal activity and sympathetic innervations to white adipose tissues. Based on these findings, we hypothesize that VMH O-GlcNAc signaling determines a body weight setpoint by means of humoral and nutritional sensing and filtering lipolytic information to white adipose tissues. To test this hypothesis, we will combine gain- and loss-of- function models with state-of-the-art neural tracing and molecular profiling tools, optogenetic and electrophysiological recordings, and comprehensive physiological assessments to delineate the mechanisms by which VMH OGT regulates adipose tissue function and constrains body weight gain. Aim 1 will determine whether O-GlcNAc signaling in VMH neurons determines the setpoint of body weight. Aim 2 will delineate the neurocircuitry by which OGT-expressing VMH neurons relay lipolytic information to white adipose tissues. Aim 3 will identify how O-GlcNAc signaling regulates hormonal and nutritional sensing of VMH neurons. A detailed understanding of body weight control by hypothalamic OGT could support the development of novel therapies for obesity and co-morbidities.


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 = $679,733 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/25/2025	NON-COMPETING CONTINUATION	$679,733
														Subtotal = $679,733

Issue Date FY: 2024 ( Subtotal = $652,546 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/26/2024	NON-COMPETING CONTINUATION	$652,546
														Subtotal = $652,546

Issue Date FY: 2023 ( Subtotal = $675,361 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/23/2023	NEW	$675,361
														Subtotal = $675,361

Grand Total All Awards = $2,007,640

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Body weight control by hypothalamic OGT

Award Number: R01DK137467

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: 08/25/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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