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The role of vascular endothelium in BAT expansion and remodeling

Award Number: K01DK125608
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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The role of vascular endothelium in BAT expansion and remodeling - Project Summary/Abstract The rising prevalence of obesity and its comorbidities is a major global health concern. The development of strategies to prevent or treat human obesity is therefore of the utmost importance. Brown adipose tissue (BAT) and its related beige fat are specialized for energy expenditure. The identification of metabolically active brown and beige fat in adult humans has positioned this tissue at the center of investigations into human energy metabolism. Considering the formidable capacity of BAT for energy expenditure and its role in fatty acid and glucose metabolism, strategies leading to increased mass or enhanced activity of BAT can potentially be utilized to combat obesity and its related metabolic disorders. Different adipose depots undergo massive remodeling in response to environmental stimuli, such as cold and diet. Prolonged cold exposure leads to recruitment of new brown adipocytes as well as a coordinated expansion and remodeling of vascular endothelium in classical BAT to enable maximal thermogenic capacity. However, the cellular origin of the cold-induced brown adipocytes, and the identity of intracellular communication pathways coordinating the adipogenesis and angiogenesis are not known. The overall goal of this proposal is to identify the role of endothelial cells in BAT expansion and remodeling in response to cold exposure and high fat diet. To address this, we used single cell RNA-sequencing (scRNA-seq) to uncover the temperature-dependent remodeling of each cell type within BAT. The preliminary data have made the novel discovery that cold exposure triggers the induction of brown adipocyte thermogenic program in endothelial cells (ECs). Additionally, the cell-type specific gene expression data allowed the identification of a Slit3-Robo4 as a potential ligand-receptor interaction mediating the crosstalk between adipocyte progenitors and ECs. The central hypotheses are that ECs contribute to cold-induced BAT expansion through de novo differentiation to thermogenic adipocytes and that Slit3 secretion from adipocyte progenitors promotes EC proliferation and angiogenesis through interaction with EC Robo4 receptor. This proposal will determine the contribution of ECs to thermogenic adipocytes pool (Aim 1) and will address the role of Slit3- Robo4 interaction in regulating adipose tissue remodeling and angiogenesis in response to high fat feeding (Aim 2). Successful completion of this proposal will change the current premise and will establish novel molecular players linking adipogenesis and angiogenesis and will have profound biomedical implications. The mentored career development award will be used to achieve a series of training objectives including expanding applicant’s knowledge in vascular biology and professional development skills that are essential for transition to an independent investigator. The training plan will build upon applicant’s expertise in adipose tissue biology and will enable the establishment of a unique cutting-edge research program in obesity and diabetes field. The team of mentors and collaborators will provide an integrative and multidisciplinary training opportunity for the applicant to receive intellectual and technical support and career development advice.


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 = -$42,590 )
2025	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	12/24/2024	SUPPLEMENT FOR EXPANSION	-$8,518
2025	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	12/24/2024	NON-COMPETING CONTINUATION	-$34,072
														Subtotal = -$42,590

Issue Date FY: 2023 ( Subtotal = $191,700 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	5/23/2023	NON-COMPETING CONTINUATION	$153,360
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	8/25/2023	SUPPLEMENT FOR EXPANSION	$38,340
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	8/25/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $191,700

Issue Date FY: 2022 ( Subtotal = $153,360 )
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	005	4	5/25/2022	NON-COMPETING CONTINUATION	$153,360
2022	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	12/7/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$108,765
2022	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/7/2021	NON-COMPETING CONTINUATION	-$108,765
2022	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	3	3/24/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$44,431
2022	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	2	3/24/2022	NON-COMPETING CONTINUATION	-$40,028
2022	2020	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	3/24/2022	NEW	-$4,403
														Subtotal = $153,360

Issue Date FY: 2021 ( Subtotal = $148,793 )
2021	2021	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	5/17/2021	NON-COMPETING CONTINUATION	$148,793
														Subtotal = $148,793

Issue Date FY: 2020 ( Subtotal = $150,293 )
2020	2020	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/22/2020	NEW	$150,293
														Subtotal = $150,293

Grand Total All Awards = $601,556

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The role of vascular endothelium in BAT expansion and remodeling

Award Number: K01DK125608

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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