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Obesity and Fat Metabolism in Human Immunodeficiency Virus-Infected Individuals: Immunopathogenic Mechanisms and Clinical Implications

dc.contributor.authorGodfrey, Catherine
dc.contributor.authorBremer, Andrew
dc.contributor.authorAlba, Diana
dc.contributor.authorApovian, Caroline
dc.contributor.authorKoethe, John R.
dc.contributor.authorKoliwad, Suneil
dc.contributor.authorLewis, Dorothy
dc.contributor.authorLo, Janet
dc.contributor.authorMcComsey, Grace A.
dc.contributor.authorEckard, Allison
dc.contributor.authorSrinivasa, Suman
dc.contributor.authorTrevillyan, Janine
dc.contributor.authorPalmer, Clovis
dc.contributor.authorGrinspoon, Steven
dc.identifier.citationCatherine Godfrey, Andrew Bremer, Diana Alba, Caroline Apovian, John R Koethe, Suneil Koliwad, Dorothy Lewis, Janet Lo, Grace A McComsey, Allison Eckard, Suman Srinivasa, Janine Trevillyan, Clovis Palmer, Steven Grinspoon, Obesity and Fat Metabolism in Human Immunodeficiency Virus–Infected Individuals: Immunopathogenic Mechanisms and Clinical Implications, The Journal of Infectious Diseases, Volume 220, Issue 3, 1 August 2019, Pages 420–431,
dc.description.abstractMetabolic complications relating to complex effects of viral and immune-mediated mechanisms are now a focus of clinical care among persons living with human immunodeficiency virus (PLHIV), and obesity is emerging as a critical problem. To address knowledge gaps, the US National Institutes of Health sponsored a symposium in May 2018 entitled Obesity and Fat Metabolism in HIV-infected Individuals. Mechanisms relating to adipose dysfunction and fibrosis, immune function, inflammation, and gastrointestinal integrity were highlighted as contributors to obesity among PLHIV. Fibrotic subcutaneous adipose tissue is metabolically dysfunctional and loses its capacity to expand, leading to fat redistribution, including visceral obesity and ectopic fat accumulation, promoting insulin resistance. Viral proteins, including viral protein R and negative regulatory factor, have effects on adipogenic pathways and cellular metabolism in resident macrophages and T cells. HIV also affects immune cell trafficking into the adipose compartments, with effects on adipogenesis, lipolysis, and ectopic fat accumulation. Key cellular metabolic functions are likely to be affected in PLHIV by gut-derived cytokines and altered microbiota. There are limited strategies to reduce obesity specifically in PLHIV. Enhancing our understanding of critical pathogenic mechanisms will enable the development of novel therapeutics that may normalize adipose tissue function and distribution, reduce inflammation, and improve insulin sensitivity in PLHIV.en_US
dc.description.sponsorshipThis publication was supported by the Office of Research in Women's Health, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Institute of Allergy and Infectious Diseases. J. R. K. is supported by NIDDK (grant number R01DK112262) and the Tennessee Center for AIDS Research (grant number P30AI110527). S. K. is supported by NIDDK (grant number 1R01DK1123) and indirectly by NIDDK-sponsored P30 grant numbers DK098722 (University of California, San Francisco [UCSF] Nutrition and Obesity Research Center) and DK063720 (UCSF Diabetes Research Center). D. L. receives support from NIAID (grant numbers R21 AI116208 and R33 AI116208). J. L., S. S., and S. G. are supported by the NIH (grant numbers R01HL123351, K23 HL136262, and P30 DK040561, respectively). J. T. is supported by an Australian National Health and Medical Research Council Early Career Fellowship. C. P. is supported by the Australian Centre for HIV and Hepatitis Virology Research (ACH2) and a 2010 developmental grant (Creative and Novel Ideas in Research) from the University of Washington Center for AIDS Research, an NIH-funded program (award number AI027757).en_US
dc.publisherThe Journal of Infectious Diseasesen_US
dc.rightsThe Journal of Infectious Diseases® 2019;220:420–31 Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/infdis/jiz118
dc.subjectviral proteinsen_US
dc.titleObesity and Fat Metabolism in Human Immunodeficiency Virus-Infected Individuals: Immunopathogenic Mechanisms and Clinical Implicationsen_US

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