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Melanin-concentrating hormone and the neural regulation of feeding

Award Number: K01DK118000
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/26/2019
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Melanin-concentrating hormone and the neural regulation of feeding - Project Summary/Abstract Obesity and its associated comorbidities pose a major burden to public health, and existing therapeutics are only minimally effective or have major adverse consequences. The brain plays a central role in mediating energy balance. Melanin-concentrating hormone (MCH), a neuropeptide produced primarily in the lateral hypothalamic area (LHA) increases energy intake and body weight gain, and therefore there is recent interest in developing obesity therapeutics that block the hyperphagic effects of MCH. Preliminary data herein suggest that in addition to generally increasing food intake, MCH contributes to excessive feeding via conditioned appetitive mechanisms, such as food impulsivity and conditioned place preference for palatable food. Furthermore, these mechanisms can be attributed to specific nodes of MCH neuronal circuitry such as the ventral hippocampus (vHP), a region that contains high levels of MCH receptor but where the function of MCH with regard to feeding behavior has not previously been investigated. Through studying the MCH system and its contributions to the central regulation of ingestive behavior, the principal goal of the proposed 5-year research career development plan is to facilitate the applicant's transition from Research Assistant Professor to Tenure-track Assistant Professor with independent R01 funding. The proposed research will enable the applicant to master several virus-based neuroanatomical and chemogenetic techniques, rodent behavioral paradigms, high- resolution whole brain mapping with functional connectivity analyses. Using these techniques, she will determine the role of MCH to vHP neuronal circuitry in mediating feeding behavior, the relevance of this pathway to obesity, and will identify collateral projections, functional connections, and downstream targets. Specific Aim 1 utilizes dual virus chemogenetic techniques to selectively activate MCH neurons that project to the vHP in order to study the role of vHPà MCH neuronal circuitry in mediating several aspects of feeding behavior. Specific Aim 2 uses viral-based neural tracing, immunohistochemistry and in situ hybridization to further characterize these neurons by their collateral projections and phenotypic gene/protein expression profiles. Aim 3 uses the novel combination of dual virus chemogenetics with whole brain perfusion mapping to determine downstream regions engaged by activating MCH neurons that project to the vHP. Additionally, experiments in Aim 3 will determine how MCH to vHP neuronal circuitry augments regional brain activity during food impulsivity. This novel combination of approaches allows for investigation of the interaction between activating specific nodes of a defined circuit and immediate behavioral effects. Results from these experiments will be generative as pilot data for an R01 submission by the applicant, will provide significant contributions to ingestive behavior research, and will overall provide the applicant with a unique set of skills for her independent research career.


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 = -$388 )
2025	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/11/2025	NON-COMPETING CONTINUATION	-$388
														Subtotal = -$388

Issue Date FY: 2023 ( Subtotal = $152,859 )
2023	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	12/21/2022	NON-COMPETING CONTINUATION	$152,859
														Subtotal = $152,859

Issue Date FY: 2022 ( Subtotal = $152,859 )
2022	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/23/2021	NON-COMPETING CONTINUATION	$152,859
														Subtotal = $152,859

Issue Date FY: 2021 ( Subtotal = $152,859 )
2021	2021	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/16/2020	NON-COMPETING CONTINUATION	$152,859
														Subtotal = $152,859

Issue Date FY: 2020 ( Subtotal = $152,859 )
2020	2020	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	12/13/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$152,859
2020	2020	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	2	1/16/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$120,549
2020	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	1/16/2020	NEW	-$120,549
2020	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/12/2019	NEW	$0
														Subtotal = $152,859

Issue Date FY: 2019 ( Subtotal = $157,971 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/26/2019	NEW	$157,971
														Subtotal = $157,971

Grand Total All Awards = $769,019

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Melanin-concentrating hormone and the neural regulation of feeding

Award Number: K01DK118000

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/26/2019

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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