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A novel adipokine suppresses leptin signaling and promotes obesity

Award Number: R01DK116872
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: 01/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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A novel adipokine suppresses leptin signaling and promotes obesity - Our long-range goal is to understand signal transduction pathways underlying energy homeostasis and how their alterations contribute to obesity and metabolic diseases. The leptin signaling pathway is considered to be the most critical anorexigenic pathway in the control of food intake and body weight. Moreover, this pathway has been demonstrated to improve glucose homeostasis independently of its effects on body weight and food intake. However, obese patients, and type 2 diabetic patients who are commonly obese, response poorly to exogenous leptin treatment, and are thus considered to be leptin resistant. Therefore, elucidating the underlying mechanisms of leptin resistance is of great medical importance. To date, whether peripheral tissues produce endocrine factors to attenuate leptin signaling remains to be explored. We identified a previously uncharacterized, adipose tissue-selectively expressed 8 kD adipokine we called Batotin. We found that this adipokine binds to leptin receptor and suppresses leptin signaling. Remarkably, transgenic mice expressing Batotin in adipose tissue are hyperphagia and morbidly obese, and have elevated blood glucose level independent of obesity. These results lead to a model that secreted Batotin from peripheral tissue acts as an orexigenic peptide in an endocrine manner to suppress leptin signaling. In Aim 1, we will investigate in detail how Batotin suppresses leptin signaling. In Aim 2, we will use gain-of-function mouse models to investigate the function and mechanism of Batotin. In Aim 3, we will study loss-of-function mouse models.


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: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $418,750 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	4/7/2022	NON-COMPETING CONTINUATION	$41,875
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/13/2021	NON-COMPETING CONTINUATION	$376,875
														Subtotal = $418,750

Issue Date FY: 2021 ( Subtotal = $418,750 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	2/5/2021	NON-COMPETING CONTINUATION	$41,875
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/8/2021	NON-COMPETING CONTINUATION	$376,875
														Subtotal = $418,750

Issue Date FY: 2020 ( Subtotal = $418,750 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	2/12/2020	NON-COMPETING CONTINUATION	$41,875
2020	2020	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/23/2019	NON-COMPETING CONTINUATION	$376,875
														Subtotal = $418,750

Issue Date FY: 2019 ( Subtotal = $418,750 )
2019	2019	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/14/2018	NEW	$418,750
														Subtotal = $418,750

Grand Total All Awards = $1,675,000

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A novel adipokine suppresses leptin signaling and promotes obesity

Award Number: R01DK116872

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: 01/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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