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Alterations to adipose tissue regulation and function by cART in SIV-infected rhesus macaques

Award Number: R01DK148251
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: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Alterations to adipose tissue regulation and function by cART in SIV-infected rhesus macaques - ABSTRACT Long-term combination antiretroviral therapy (cART) has significantly improved the management of HIV, but it comes with complications. Over 75% of chronic HIV patients on cART experience clinical issues, with a notable one being lipodystrophy, which is characterized by abnormal fat redistribution and metabolism. Adipose tissue, composed of fat cells (adipocytes) and their precursors (adipose stem cells or ASCs), plays a central role in these complications. HIV and cART can compromise these cells, leading to altered fat distribution, inflammation, and accelerated aging, or “inflammaging”. The virus and its proteins initially expose the adipose cells to the effects of the infection. Later, cART drugs are also introduced, further affecting the cellular processes. Together, these decrease the maturation of ASCs into functional adipocytes, which in turn disrupts fat metabolism. To investigate this, we propose using a rhesus macaque/SIV-infection model. This model will allow us to test the hypothesis that both the virus and antiretroviral drugs contribute to accelerated aging and adipose tissue dysfunction. We will assess the effects of infection alone, cART alone, and their combination on adipocytes and ASCs. This study is innovative because we will longitudinally assess ASCs and adipocytes from the same animals before and after SIV infection and cART treatment. We will also perform real-time measurements of adipocyte function. We will track changes in fat distribution using CT imaging, advanced digital immunohistochemistry, and flow cytometry of biopsies. The mechanisms behind these alterations will be determined before and after necropsy. Our team is highly qualified to perform this research, with extensive experience in studying ASCs and adipocytes in non-human primates and expertise in longitudinal sampling in SIV-infected monkeys. The findings will provide crucial mechanistic insights into adipogenesis, adipocyte function, and obesity in the context of long-term cART.


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 = $882,709 )
2026	2026	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/1/2026	NEW	$882,709
														Subtotal = $882,709

Grand Total All Awards = $882,709

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Alterations to adipose tissue regulation and function by cART in SIV-infected rhesus macaques

Award Number: R01DK148251

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: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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