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Brief Report

Adipogenic Expression of Brown Fat Genes in HIV and HIV-Related Parameters

Srinivasa, Suman MDa; Torriani, Martin MDa,b; Fitch, Kathleen V. MSNa; Maehler, Patrick BSa; Iyengar, Sanjna BSa; Feldpausch, Meghan MSNa; Cypess, Aaron M. MD, PhDc; Grinspoon, Steven K. MDa

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15, 2019 - Volume 82 - Issue 5 - p 491–495
doi: 10.1097/QAI.0000000000002180
Translational Research
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Context: Persons with HIV are at increased risk for adipose dysfunction, which could mediate metabolic complications such as cardiovascular disease, fatty liver disease, and diabetes. We have previously reported reduced browning and beiging capacity of the subcutaneous adipose depot in HIV.

Objective: We sought to evaluate how HIV-related parameters are related to the expression of brown and beige fat genes in the abdominal subcutaneous adipose tissue.

Design: Eighteen persons with HIV underwent punch biopsy of abdominal subcutaneous fat to determine mRNA expression of adipose-related genes using quantitative reverse transcriptase-polymerase chain reaction.

Results: Duration of antiretroviral therapy use, particularly related to protease inhibitor use, was significantly related to reduced expression of multiple brown and beige fat genes (including UCP1, PGC1α, PRDM16 and others, all P ≤ 0.04) in the abdominal subcutaneous fat. In addition, duration of HIV and CD4 T-cell count were significantly correlated with reduced expression of multiple brown and beige fat genes in the abdominal subcutaneous fat (PGC1α, P2XR5, TMEM26, CD137, all P ≤ 0.05 for duration of HIV; and PGC1α, ZIC1, PRDM16, PAT2, P2RX5, TMEM26, CD137, all P ≤ 0.04). In contrast, HIV viral load did not correlate with any brown or beige fat genes.

Conclusions: Key HIV-related parameters reflective of nonacute infection (increased duration of HIV and duration of antiretroviral therapy use) or relatively reduced immunologic function (lower CD4 count) were linked to reduced expression of brown and beige fat gene in the abdominal subcutaneous adipose depot.

Clinical Trial Registration: NCT01098045.

aMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA;

bDivision of Musculoskeletal Imaging and Intervention, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and

cTranslational Physiology Section, Diabetes, Endocrinology, and Obesity Branch, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.

Correspondence to: Steven K. Grinspoon, MD, Metabolic Unit, Massachusetts General Hospital, 55 Fruit Street, LON207, Boston, MA 02114 (e-mail: sgrinspoon@mgh.harvard.edu).

Supported by the NIH Grants K23HL136262 to S.S., M01RR01066, UL1RR025758, and UL1TR001102 to the Harvard Catalyst/Harvard Clinical and Translational Science Center from the National Center for Research Resources and National Center for Advancing Translational Sciences, and P30DK40561, Pilot and Feasibility Grant to the Nutrition and Obesity Research Center at Harvard.

M.T., P.M., S.I., M.F., and A.M.C. have nothing to declare. S.S. and K.V.F. have been supported by an educational grant from Gilead Sciences and Merck to participate in a CME activity; S.S. has received research funding from Gilead Sciences; S.K.G. has received research funding from Gilead, KOWA, and Theratechnologies and served as a consultant for Theratechnologies; all disclosures from all authors are unrelated to this manuscript.

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Received July 18, 2019

Accepted September 02, 2019

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