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Immune-adipocyte Crosstalk in Adipose-selective Thermogenic Program

Award Number: F32DK141191
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: 09/03/2025
PERIOD OF PERFORMANCE END DATE: 09/02/2028

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Immune-adipocyte Crosstalk in Adipose-selective Thermogenic Program - Project Summary Immune cells are an integral part of the adipose microenvironment and have pronounced effects on the expansion and activation of thermogenic adipocytes, also known as beige/brite adipocytes. Anti-inflammatory factors are postulated to be beneficial for insulin resistance and diabetes. Our lab recently reported that ablation of interleukin-10 (IL10)-associated anti-inflammatory signaling in mice, surprisingly, improved insulin sensitivity and glucose tolerance, protected against diet-induced obesity, and elicited browning of white adipose tissue. My proposal builds upon comprehensive data to address the crosstalk between immune cells and adipocytes within adipose tissue depots in regulating adipose thermogenesis. Our published and pilot studies show that interfering with IL10 activity in adipocytes is associated with increased thermogenesis, mitochondrial respiration, and energy expenditure. Ablation of adipose T cells increased adipose thermogenesis, pointing to a hematopoietic origin of the IL-10 signal regulating adipose tissue function. The IL10 receptor alpha (IL10R) is highly expressed in mature adipocytes, and adipocyte-specific knockdown of IL10R decreases fat mass and increases adipose thermogenesis, energy expenditure, and lipolysis. Conversely, IL10 treatment directly antagonizes the expression of thermogenic and lipolytic genes in a cell-autonomous manner. Furthermore, genome-wide Assay for Transposase-Accessible Chromatin (ATAC)-seq, ChIP-seq, and RNA-seq demonstrated that IL-10 represses the transcription of thermogenic genes by altering chromatin configuration at key enhancer and promoter regions. Our findings identify the “IL10-IL10R axis” as a novel regulator of the thermogenic transcriptional program in adipose tissue and challenge conventional assumptions regarding links between immune and inflammatory signaling and adipose tissue function in obesity. To further test the hypothesis that adipose-specific IL10R directly “senses” IL10 in the microenvironment to limit adipose thermogenesis and promote obesity-related traits I propose three Specific Aims: i) to define the therapeutic potential of ablating IL10R in the adipocytes of adult obese mice; ii) to identify IL10 secreting immune cells, and iii) to determine the mechanism by which IL10 controls adipocyte thermogenic program. Immune cells are an integral part of the adipose microenvironment; thus, studying how IL10 modulates adipocyte regulatory processes should advance our knowledge beyond inflammation and anti-inflammation and inform future therapy for obesity and insulin resistance.


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: 2026 ( Subtotal = $84,148 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/28/2026	NON-COMPETING CONTINUATION	$84,148
														Subtotal = $84,148

Issue Date FY: 2025 ( Subtotal = $78,040 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/3/2025	NEW	$78,040
														Subtotal = $78,040

Grand Total All Awards = $162,188

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Immune-adipocyte Crosstalk in Adipose-selective Thermogenic Program

Award Number: F32DK141191

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: 09/03/2025

PERIOD OF PERFORMANCE END DATE: 09/02/2028

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