Differentially Altered Molecular Signature of Visceral Adipose Tissue in HIV-1Associated Lipodystrophy

Gallego-Escuredo, José M. PhD*,†,‡; Villarroya, Joan PhD*,†,§,‖; Domingo, Pere MD, PhD§,‖; Targarona, Eduard M. MD; Alegre, Marta MD, PhD#; Domingo, Joan C. PhD*,†,‡; Villarroya, Francesc PhD*,†,‡; Giralt, Marta PhD*,†,‡

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 October 2013 - Volume 64 - Issue 2 - p 142–148
doi: 10.1097/QAI.0b013e31829bdb67
Basic and Translational Science

Objective: Lipodystrophy in HIV-1–infected antiretroviral-treated patients is often associated with opposite alterations in adipose tissue depots as follows: lipoatrophy of subcutaneous adipose tissue (SAT) versus lipohypertrophy of visceral adipose tissue (VAT). We determined the specific molecular alterations in VAT relative to SAT in patients.

Design: We analyzed the expression of marker genes of mitochondrial function, adipogenesis, and inflammation in a unique collection of 8 biopsies of omental VAT from HIV-1–infected antiretroviral-treated patients with lipodystrophy. For comparison, we analyzed SAT from 10 patients, and SAT and VAT from 10 noninfected individuals.

Methods: Quantitative real-time polymerase chain reaction of mitochondrial DNA and gene transcripts; immunoblot and multiplex for quantification of specific proteins.

Results: Similar mitochondrial DNA depletion and abnormal increases in mitochondrial protein levels were found in VAT and SAT from patients. Transcript levels of adipogenesis and metabolism marker genes were unaltered in VAT but were decreased in SAT. Tumor necrosis factor α and CD68 were similarly induced in both adipose depots from patients, but other markers of inflammation-related pathways showed distinct alterations as follows: interleukin 18 and interleukin 1 receptor antagonist were induced only in SAT, whereas interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 expression was reduced in VAT but not in SAT.

Conclusions: Mitochondrial alterations are similar in VAT and SAT from patients, whereas adipogenic gene expression is decreased in SAT but unaltered in VAT, highlighting the relevance of adipogenic processes in the differential alterations of fat depots. Specific disturbances in inflammatory status in VAT relative to SAT are present. Milder induction of proinflammatory signaling in VAT could be involved in preventing fat wasting in this depot.

*Department of Biochemistry and Molecular Biology; and

Institut de Biomedicina (IBUB), University of Barcelona, Barcelona, Spain;

CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain;

§Red de Investigación en SIDA (RIS), Barcelona, Spain; and

Departments of Infectious Diseases;

General Surgery; and

#Dermatology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.

Correspondence to: Dr Marta Giralt, PhD, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Avda Diagonal 643, E-08028-Barcelona, Catalonia, Spain (e-mail: mgiralt@ub.edu).

The authors have no conflicts of interest to disclose.

Supported by Fondo de Investigaciones Sanitarias (grants PI08/1715, PI11/02512 and PI11/00376) and Red de Investigación en SIDA (grant RD06/0006/0022) from the Instituto de Salud Carlos III, Spain; Ministerio de Economía y Competividad, Spain (grant SAF2011-23636); and AGAUR-Generalitat de Catalunya (grant 2009-SGR284).

The authors J.M.G-E. and J.V. contributed equally to the study.

Received December 05, 2012

Accepted May 14, 2013

© 2013 by Lippincott Williams & Wilkins