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Visceral fat is associated with brain structure independent of human immunodeficiency virus infection status

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Abstract

The combined effects of human immunodeficiency virus (HIV), obesity, and elevated visceral adipose tissue (VAT) on brain structure are unknown. In a cross-sectional analysis of Multicenter AIDS Cohort Study (MACS) participants, we determined associations between HIV serostatus, adiposity, and brain structure. Men (133 HIV+, 84 HIV–) in the MACS Cardiovascular 2 and magnetic resonance imaging (MRI) sub-studies with CT-quantified VAT and whole brain MRI measured within 1 year were assessed. Voxel-based morphometry analyzed brain volumes. Men were stratified by elevated (eVAT, ≥100cm2) or “normal” (nVAT, <100cm2) VAT. Forward stepwise modeling determined associations between clinical and demographic variables and regional brain volumes. eVAT was present in 67% of men. Groups were similar in age and education, but eVAT men were more likely to be HIV+ and have hypertension, diabetes mellitus, body mass index >25 kg/m2, smaller gray and white matter volumes, and larger cerebrospinal fluid volume than nVAT men. In multivariate analysis, hypertension, higher adiponectin, higher interleukin-6, age, diabetes mellitus, higher body mass index, and eVAT were associated with brain atrophy (p < 0.05, ordered by increasing strength of association), but HIV serostatus and related factors were generally not. No interactions were observed. Greater VAT was associated with smaller bilateral posterior hippocampus and left mesial temporal lobe and temporal stem white matter volume. Traditional risk factors are more strongly associated with brain atrophy than HIV serostatus, with VAT having the strongest association. However, HIV+ MACS men had disproportionately greater VAT, suggesting the risk for central nervous system effects may be amplified in this population.

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Acknowledgements

Data in this manuscript were collected by the MACS with centers at Baltimore (U01-AI35042): The Johns Hopkins University Bloomberg School of Public Health: Joseph B. Margolick (PI), Jay Bream, Todd Brown, Barbara Crain, Adrian Dobs, Richard Elion, Richard Elion, Michelle Estrella, Lisette Johnson-Hill, Sean Leng, Anne Monroe, Cynthia Munro, Michael W. Plankey, Wendy Post, Ned Sacktor, Jennifer Schrack, Chloe Thio; Chicago (U01-AI35039): Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services: Steven M. Wolinsky (PI), John P. Phair, Sheila Badri, Dana Gabuzda, Frank J. Palella, Jr., Sudhir Penugonda, Susheel Reddy, Matthew Stephens, Linda Teplin; Los Angeles (U01-AI35040): University of California, UCLA Schools of Public Health and Medicine: Roger Detels (PI), Otoniel Martínez-Maza (Co-PI), Aaron Aronow, Peter Anton, Robert Bolan, Elizabeth Breen, Anthony Butch, Shehnaz Hussain, Beth Jamieson, Eric N. Miller, John Oishi, Harry Vinters, Dorothy Wiley, Mallory Witt, Otto Yang, Stephen Young, Zuo Feng Zhang; Pittsburgh (U01-AI35041): University of Pittsburgh, Graduate School of Public Health: Charles R. Rinaldo (PI), Lawrence A. Kingsley (Co-PI), James T. Becker, Phalguni Gupta, Kenneth Ho, Susan Koletar, Jeremy J. Martinson, John W. Mellors, Anthony J. Silvestre, Ronald D. Stall; Data Coordinating Center (UM1-AI35043): The Johns Hopkins University Bloomberg School of Public Health: Lisa P. Jacobson (PI), Gypsyamber D’Souza (Co-PI), Alison Abraham, Keri Althoff, Jennifer Deal, Priya Duggal, Sabina Haberlen, Alvaro Muoz, Derek Ng, Janet Schollenberger, Eric C. Seaberg, Sol Su, Pamela Surkan. Institute of Allergy and Infectious Diseases (NIAID): Robin E. Huebner; National Cancer Institute (NCI): Geraldina Dominguez. The MACS website is located at http://www.statepi.jhsph.edu/macs/macs.html. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH).

The authors would also like to thank the staff at the University of Vermont Laboratory for Clinical Biochemistry Research for their assistance with biomarker measurement.

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Authors and Affiliations

  1. Center for Clinical AIDS Research and Education, University of California, Los Angeles, CA, USA

    Jordan E. Lake

  2. University of Texas Health Science Center at Houston, 6431 Fannin St., MSB 2.112, Houston, TX, 77030, USA

    Jordan E. Lake

  3. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    Mikhail Popov & James T. Becker

  4. Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Wendy S. Post & Todd T. Brown

  5. Department of Medicine, Northwestern University, Chicago, IL, USA

    Frank J. Palella

  6. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA

    Ned Sacktor

  7. Department of Psychiatry and Bio-behavioral Sciences, University of California, Los Angeles, CA, USA

    Eric N. Miller

  8. Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA

    James T. Becker

  9. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

    James T. Becker

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  1. Jordan E. Lake
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  2. Mikhail Popov
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Correspondence to Jordan E. Lake.

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Funding

The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases, with additional co-funding from the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute of Mental Health. Targeted supplemental funding for specific projects was provided by the National Heart, Lung, and Blood Institute and the National Institute on Deafness and Communication Disorders. MACS data collection is also supported by UL1-TR001079 (Johns Hopkins University Institute for Clinical and Translational Research) from the National Center for Advancing Translational Sciences, a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the NIH, Johns Hopkins Institute for Clinical and Translational Research, or the National Center for Advancing Translational Sciences. Additional support for data analysis and manuscript preparation was provided by NIH grants AG034852 and MH098745 to JTB, K23AI110532 to JEL, K24 AI120834 to TTB, P30 AG028748, and P30 AI028697.

Conflict of interest

JEL has served as a consultant to Gilead Sciences and GlaxoSmithKline. ENM is the author of the reaction time software used in this study (CalCAP) and has a financial interest in the software. TTB has served as a consultant to AbbVie, EMD-Serono, Merck, ViiV Healthcare and Gilead Sciences. MP, WSP, FJP, NS, and JTB declare that they have no conflict of interest.

Additional information

Dr. Lake has recently transitioned to the University of Texas Health Science Center at Houston, but the work was performed during her affiliation with UCLA, as stated.

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Lake, J.E., Popov, M., Post, W.S. et al. Visceral fat is associated with brain structure independent of human immunodeficiency virus infection status. J. Neurovirol. 23, 385–393 (2017). https://doi.org/10.1007/s13365-016-0507-7

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