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Regulation of thermogenesis by the novel brown adipose-specific protein BASIC

Award Number: F30DK123986
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: 12/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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Regulation of thermogenesis by the novel brown adipose-specific protein BASIC - PROJECT SUMMARY Failure to maintain systemic energy homeostasis—a balance between energy intake and energy expenditure at the organismal level—is the root cause of obesity and its associated comorbidities. As a result, physiological processes that regulate energy intake and/or expenditure are the subject of intense study and hold great promise as therapeutic targets for obesity. Stimulation of nonshivering thermogenesis (NST)—the generation of heat by futile metabolic cycling in brown (BAT) and beige adipose tissue—has garnered considerable interest as a potential means of increasing energy expenditure in humans to protect against obesity and the metabolic syndrome. However, NST-based therapeutic strategies are limited by the adverse effects of inducing futile cycling in non-BAT tissues. Thus, identifying and characterizing novel BAT-specific proteins could provide opportunities for the development of improved obesity interventions targeting NST. Preliminary studies employing next-generation sequencing, molecular biology, genome editing, and proteomic approaches have led to the discovery of a novel BAT-specific protein of unknown function named BASIC. Basic expression is highly induced by environmental and pharmacological activators of NST in mice, and knockdown of BASIC appears to upregulate the thermogenic gene program in cultured adipocytes, implicating BASIC as a cell- intrinsic negative regulator of adipose thermogenesis. The proposed research plan will first use physiologic and molecular approaches to characterize a newly generated BASIC knockout mouse model and thereby determine the consequence of loss of BASIC function on NST in vivo (Aim 1). Further studies will elucidate BASIC's mechanism of action by defining its subcellular localization and examining its effect on thermogenic signaling pathways in primary brown adipocytes (Aim 2). Completion of the proposed aims will shed light on the function of a hitherto undiscovered BAT-specific protein, which may provide insight into new pathways involved in adipose thermogenesis and reveal a potential target for NST-based therapeutic interventions.


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 = -$11,310 )
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	6/24/2024	NON-COMPETING CONTINUATION	$0
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/10/2024	NON-COMPETING CONTINUATION	-$11,310
														Subtotal = -$11,310

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/25/2022	NON-COMPETING CONTINUATION	$51,752
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	3/7/2023	NON-COMPETING CONTINUATION	$942
														Subtotal = $52,694

Issue Date FY: 2022 ( Subtotal = $51,752 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/18/2021	NON-COMPETING CONTINUATION	$51,036
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	5/26/2022	NON-COMPETING CONTINUATION	-$1
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	4/21/2022	NON-COMPETING CONTINUATION	$717
														Subtotal = $51,752

Issue Date FY: 2021 ( Subtotal = $37,808 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/25/2020	NON-COMPETING CONTINUATION	$37,292
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	2/18/2021	NON-COMPETING CONTINUATION	$516
														Subtotal = $37,808

Issue Date FY: 2019 ( Subtotal = $36,788 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/10/2019	NEW	$36,788
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	9/10/2019	NEW	$0
														Subtotal = $36,788

Grand Total All Awards = $167,732

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Regulation of thermogenesis by the novel brown adipose-specific protein BASIC

Award Number: F30DK123986

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: 12/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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