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Resolving the effects of dietary fat induced maternal CXCL12 on offspring hypothalamus using spatial gene transcriptomics

Award Number: R03HD109543
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/18/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Resolving the effects of dietary fat induced maternal CXCL12 on offspring hypothalamus using spatial gene transcriptomics - PROJECT SUMMARY Excessive intake of a diet rich in fats during pregnancy gives rise to offspring that are prone to overeating dietary fat and becoming obese. This generational effect of prenatal programming of ingestive behavior results in offspring that are prone to becoming obese. This proneness in offspring is attributed to an increase in the genesis of orexigenic enkephalin neurons in the hypothalamus. High levels and expression of hypothalamic enkephalin is a stimulator of high-fat diet intake. One potential mechanism for this change involves the chemokine CXCL12, which has been shown to be altered by the intake of a high-fat diet. Maternal CXCL12, similar to a high-fat diet, can also stimulate enkephalin levels and ingestive behavior in offspring. Currently, it is unknown how prenatal high-fat diet exerts its affects through CXCL12 to change the hypothalamic architecture in developing embryos. The goal of this proposal in using a rat model is pilot whether the reduction of maternal CXCL12 levels could prevent offspring brain changes. Aim 1a will examine the effects of CXCL12-neutralizing antibody paired with maternal HFD ingestion on changes in offspring hypothalamus. Utilizing the novel spatial gene transcriptome technique, immunofluorescence histology labeling of neurons and neuroglia in conjunction with markers of genesis and orexigenic neuropeptides will be performed. Afterwards, discrete regions of the hypothalamus will be barcoded, and the mRNA (resulting cDNA) will be collected for RNAseq. The results will provide unique location-based transcriptome changes overlaid by fluorescently labeled cell types. Aim 1b will test these same offspring for behavioral and weight changes that align with obesity-prone rats. Daily caloric intake and weight change will be tracked and behavioral tests to measure anxiety-like behavior, a marker for hyperphagia, will also be examined. These results will further support the hypothesis that HFD-induced increase in maternal CXCL12 plays a role in producing hyperphagic offspring and provide new higher resolution insight into neurogenesis events in offspring brain.


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 = -$17 )
2026	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	CAMPUS RM H402	OLD WESTBURY	NY	11568	NASSAU	USA	Child Health and Human Development Extramural Research	000	2	6/8/2026	NON-COMPETING CONTINUATION	-$17
														Subtotal = -$17

Issue Date FY: 2023 ( Subtotal = $79,850 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	CAMPUS RM H402	OLD WESTBURY	NY	11568	NASSAU	USA	Child Health and Human Development Extramural Research	000	2	6/26/2023	NON-COMPETING CONTINUATION	$79,850
														Subtotal = $79,850

Issue Date FY: 2022 ( Subtotal = $79,850 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	CAMPUS RM H 402 A	OLD WESTBURY	NY	11568	NASSAU	USA	Child Health and Human Development Extramural Research	000	1	8/18/2022	NEW	$79,850
														Subtotal = $79,850

Grand Total All Awards = $159,683

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Resolving the effects of dietary fat induced maternal CXCL12 on offspring hypothalamus using spatial gene transcriptomics

Award Number: R03HD109543

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/18/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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