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The Impact of Early Life Stress on Reward and Body Weight

Award Number: F32DK127693
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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The Impact of Early Life Stress on Reward and Body Weight - PROJECT SUMMARY My long-term professional goal is to become a successful, independent scientist with a research program focused on obesity and the neurobiological regulation of feeding and activity in response to exercise. Obesity continues to be a major health concern and obesity risk is increased with exposure to early life stress. Exposure to early life stress is very common in the United States and yet we do not fully understand how early stress alters reward neurocircuitry to affect the motivation to consume palatable foods and be physically active. The reward system control of body weight relies on the inherently rewarding value of foods, particularly those high in fat and sugar, and of physical activity. Within the brain, the motivation to obtain these natural rewards is driven by dopaminergic activity in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Glucocorticoid receptors are found throughout reward regions of the brain and chronic hypercorticosteronemia, such as that associated with early life stress exposure, has been shown to inhibit dopamine release and turnover in the NAc. Additionally, one of the greatest issues facing individuals with obesity is the failure of weight loss programs to produce meaningful and sustained weight loss. It is unknown whether early life stress worsens the maintenance of lost weight or whether exercise, which is the greatest predictor of weight loss maintenance success, is effective in individuals that have experienced early life stress. Our overall hypothesis is that early life stress impairs reward processing and homeostasis of body weight, which can be partially mitigated by voluntary wheel running. We will test this overall hypothesis using neonatal maternal separation (NMS) in mice, a preclinical model of early life stress. In Aim 1, we will determine if early life stress alters reward sensitivity in response to high fat/high sucrose diet-induced obesity and calorie-restricted weight loss. We expect that NMS mice will display hypercorticosteronemia, which will be negatively associated with dopamine turnover and release in the NAc and VTA. We also anticipate that NMS mice will display altered reward motivation when challenged with behavioral tests during diet-induced obesity and weight loss. In Aim 2, we will test if early life stress potentiates weight regain and metabolic dysfunction and identify whether exercise can counter these early life stress-induced impairments. We anticipate that NMS will cause an increased rate of weight regain, inflammation, and metabolic dysfunction after being allowed to refeed ad libitum following calorie-restricted weight loss. We expect that voluntary wheel running will attenuate weight regain and metabolic dysfunction in naïve mice to a greater extent than in NMS mice. Given the increasing prevalence of both obesity and early life stress, it is highly likely that this is an interaction impacting clinical weight loss maintenance. It is vitally important to understand how early life stress alters reward motivation and weight loss maintenance success to allow for the development of improved weight loss maintenance therapies and better outcomes in obesity treatments.


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 = $0 )
2025	2023	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/23/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $71,792 )
2023	2023	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/28/2023	NON-COMPETING CONTINUATION	$71,792
														Subtotal = $71,792

Issue Date FY: 2022 ( Subtotal = $67,582 )
2022	2022	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/20/2022	NON-COMPETING CONTINUATION	$67,581
2022	2022	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/26/2022	NON-COMPETING CONTINUATION	$1
														Subtotal = $67,582

Issue Date FY: 2021 ( Subtotal = $65,994 )
2021	2021	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/8/2021	NEW	$65,994
2021	2021	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	3/8/2021	NEW	$0
														Subtotal = $65,994

Grand Total All Awards = $205,368

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The Impact of Early Life Stress on Reward and Body Weight

Award Number: F32DK127693

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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