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Dissecting the thermogenic adipose niche

Award Number: R01DK133528
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: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Dissecting the thermogenic adipose niche - Project Summary/Abstract Adipose tissue plays a critical role in the regulation of whole-body energy metabolism, and adipose dysfunction directly links to the etiology of several commonly seen metabolic diseases, such as type 2 diabetes mellitus and cardiovascular diseases. There are several different adipose depots dispersed throughout the body. White adipose tissue (WAT) is the primary site of the triglyceride storehouse. In contrast, thermogenic fat, which consists of classical brown adipose tissue (BAT) and inducible beige/brite fat, is specialized for thermogenic energy expenditure. In humans, individuals with detectable BAT have a significantly lower prevalence of cardiometabolic diseases, pointing to the metabolic benefits and therapeutic promise of BAT. Thermogenic adipose tissue can rapidly respond to environmental challenges by modulating cellular compositions and cell- to-cell interactions. Such adaptation is key to maintaining metabolic health. Intercellular communications within the thermogenic adipose niche orchestrate adipose tissue development and play an essential role in adipose tissue turnover, expansion, and remodeling in response to external stimuli. To dissect the complex cellular makeup of thermogenic fat, we performed single-cell RNA-sequencing analysis of BAT from mice housed at different temperatures. The results revealed a high degree of heterogeneity of thermogenic adipose niche and showed cold exposure induced dynamic changes of cellular composition in BAT. Importantly, we identified a novel population of adipose progenitor cells (APCs), which was derived from the vascular smooth muscle (VSM) lineage and uniquely expressed Trpv1 (transient receptor potential cation channel subfamily V member 1). Lineage tracing studies demonstrated that the Trpv1-expressing VSM-APCs could proliferate and differentiate into highly thermogenic adipocytes in response to cold stimulation. Work in progress showed that impaired adipogenic differentiation of Trpv1-expressing APCs resulted in reduced expression of thermogenic genes in BAT and WAT, suggesting an important role of these cells in thermoregulation. Additional preliminary data showed that the Trpv1-expressing APCs could respond to local signals and differentiate into thermogenic adipocytes. These exciting findings have led us to propose a model involving intercellular communications in which interplays between the APCs and inductive signals shapes adipocyte differentiation and function. In this proposal, we will test this hypothesis by determining the physiological role of the Trpv1-expressing APCs in metabolic regulation, identifying the endogenous and exogenous stimuli of Trpv1-positive APCs, and mapping the cellular interactome of the thermogenic adipose niche using computational tools and spatial transcriptomic analysis. Successful completion of the proposed studies will provide new insight into the role of intercellular communications in the regulation of adipose tissue development and function.


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 = $701,614 )
2025	2025	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	8/11/2025	NON-COMPETING CONTINUATION	$701,614
														Subtotal = $701,614

Issue Date FY: 2024 ( Subtotal = $679,560 )
2024	2024	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/27/2024	NON-COMPETING CONTINUATION	$679,560
														Subtotal = $679,560

Issue Date FY: 2023 ( Subtotal = $714,937 )
2023	2023	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/30/2023	NON-COMPETING CONTINUATION	$714,937
														Subtotal = $714,937

Issue Date FY: 2022 ( Subtotal = $739,622 )
2022	2022	JOSLIN DIABETES CENTER, INC.	1 JOSLIN PL	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/29/2022	NEW	$739,622
														Subtotal = $739,622

Grand Total All Awards = $2,835,733

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Dissecting the thermogenic adipose niche

Award Number: R01DK133528

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: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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