Prolonged Antiretroviral Treatment Induces Adipose Tissue Remodelling Associated with Mild Inflammation in SIV-Infected Macaques

Cells. 2022 Oct 2;11(19):3104. doi: 10.3390/cells11193104.

Abstract

During chronic SIV/HIV infection, adipose tissue (AT) is the target of both antiretroviral treatment (ART) and the virus. AT might subsequently contribute to the low-grade systemic inflammation observed in patients on ART. To evaluate the inflammatory profile of AT during chronic SIV/HIV infection, we assayed subcutaneous and visceral abdominal AT from non-infected (SIV-, control), ART-naïve SIV-infected (SIV+) and ART-controlled SIV-infected (SIV+ART+) cynomolgus macaques for the mRNA expression of genes coding for factors related to inflammation. Significant differences were observed only when comparing the SIV+ART+ group with the SIV+ and/or SIV- groups. ART-treated infection impacted the metabolic fraction (with elevated expression of PPARγ and CEBPα), the extracellular matrix (with elevated expression of COL1A2 and HIF-1α), and the inflammatory profile. Both pro- and anti-inflammatory signatures were detected in AT, with greater mRNA expression of anti-inflammatory markers (adiponectin and CD163) and markers associated with inflammation (TNF-α, Mx1, CCL5 and CX3CL1). There were no intergroup differences in other markers (IL-6 and MCP-1). In conclusion, we observed marked differences in the immune and metabolic profiles of AT in the context of an ART-treated, chronic SIV infection; these differences were related more to ART than to SIV infection per se.

Keywords: HIV; SIV; adipose tissue; chronic inflammation; immune alteration; metabolic changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin
  • Adipose Tissue / metabolism
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Anti-Retroviral Agents / pharmacology
  • Anti-Retroviral Agents / therapeutic use
  • HIV
  • HIV Infections*
  • Inflammation / complications
  • Interleukin-6
  • Macaca fascicularis
  • Macaca mulatta
  • PPAR gamma
  • RNA, Messenger / therapeutic use
  • Simian Acquired Immunodeficiency Syndrome* / drug therapy
  • Simian Immunodeficiency Virus*
  • Tumor Necrosis Factor-alpha

Substances

  • Adiponectin
  • Anti-Inflammatory Agents
  • Anti-Retroviral Agents
  • Interleukin-6
  • PPAR gamma
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha

Grants and funding

This research was funded by the French National Agency for AIDS, Hepatitis, and Emerging Infectious Disease (ANRS-MIE; grant number: ECTZ103291) and the Fonds de Dotation Villa M (Paris, France). The pVISCONTI study was funded through a MSDAVENIR grant to the RHIVIERA consortium.