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Transfer application - Leptin in the VMH and energy balance

Award Number: R01DK132673
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: 09/19/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Transfer application - Leptin in the VMH and energy balance - Leptin was identified as a potential feedback signal in the regulation of energy balance in 1994, but little progress has been made in using leptin to prevent or reverse human obesity. This may be due to a failure to fully understand the central mechanisms by which leptin can control food intake which can only be evaluated when they are functioning normally. Control of energy balance is often investigated in models in which components of the system have been genetically modified, the animal has been fed an obesogenic diet or pharmacologic doses of leptin are used to investigate an endogenous physiologic system. Preliminary data using threshold doses of leptin in normal weight animals demonstrate the presence of a leptin sensitive pathway that inhibits food intake when circulating leptin concentrations rise above basal levels as a signal of positive energy balance. We have demonstrated that activation of leptin receptors in the hindbrain nucleus of the solitary tract (NTS) lowers the threshold for activation of hypothalamic leptin receptors through a neural network. This effect is most dramatic in the dorsomedial ventromedial nucleus of the hypothalamus (VMHdm), where there is a 3-fold increase in leptin receptor activation. Additional experiments demonstrated that loss of NTS leptin-receptor expressing cells raised the threshold for a hypothalamic response to leptin and that loss of leptin receptor expressing cells in the VMHdm abolished weight loss caused by hindbrain infusions of leptin. Based on these data and evidence that hypothalamic leptin suppresses food intake by amplifying the response to peripheral satiety signals, we hypothesize that small increases in circulating leptin amplify the response to peripheral satiety signals through a circuit in which NTS leptin enhances VMHdm leptin sensitivity. This application will establish the function and anatomy of the hypothesized network. The first Aim will test whether activation of VMHdm leptin receptors amplifies the response to peripheral satiety signals. The second Aim will test whether these receptors protect against diet-induced obesity. The third Aim will use tract tracing to identify the organization of the proposed neural network and in situ hybridization to identify the neurochemical phenotype of leptin receptor-expressing neurons in the NTS and VMHdm. Successful completion of these Aims will provide new information on the synergy between long-term signals of energy balance and peripheral short-term satiety signals as an integral component of a network that facilitates precise control of energy balance.


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 = $377,500 )
2025	2025	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	8/20/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$377,500
2025	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $377,500

Issue Date FY: 2024 ( Subtotal = $374,400 )
2024	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/18/2024	NON-COMPETING CONTINUATION	$374,400
														Subtotal = $374,400

Issue Date FY: 2023 ( Subtotal = $390,000 )
2023	2023	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/31/2023	NON-COMPETING CONTINUATION	$390,000
2023	2022	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/25/2023	NEW	$0
														Subtotal = $390,000

Issue Date FY: 2022 ( Subtotal = $390,000 )
2022	2022	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/19/2022	NEW	$390,000
														Subtotal = $390,000

Grand Total All Awards = $1,531,900

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Transfer application - Leptin in the VMH and energy balance

Award Number: R01DK132673

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: 09/19/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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