title: Deciphering the molecular mechanisms involved in HIV-associated lipoatrophy by transcriptomics: a pilot study.
abstract: HIV-associated lipoatrophy (LA) has considerable implications for risk of metabolic diseases, quality of life, and adherence to treatments. Although it has decreased in high-income countries, it is still very common in resource-limited countries. Understanding the pathophysiological mechanisms of LA can open the possibility to explore new ways to treat or prevent this condition. To identify new markers for an accurate and quick diagnosis will be also of interest. Thus, we aimed to examine functional classes of genes implicated in LA and to identify potential new markers for an accurate/quick diagnosis of LA and future complications. Eighteen participants were recruited: seven healthy volunteers, five non-LA-HIV patients, and six LA-HIV subjects. Clinical lipoatrophy was considered when changes in fat volume in the cheeks next to the nose, lateral aspect of the face, legs, arms, and buttocks were observed by the physicians. mRNA was isolated from peripheral blood mononuclear cells (PBMCs) to perform a transcriptomic and Gene Ontology analysis. To confirm RNA sequencing results, qPCRs were developed. A total of 55 genes were differentially expressed between LA and non-LA patients. Thirty-seven genes were overexpressed, whereas 18 genes were repressed. Functional analysis showed that overexpressed genes were involved in lymphocyte/neutrophil activation, inflammation, and atherogenesis. Several lymphoma markers and members of the lipocalin and aquaporin families were also found more expressed in LA patients. In contrast, most of the genes found less expressed in LA subjects were involved in angiogenesis and protection against myocardial infarction. Our results demonstrated a distinct transcriptomic signature in PBMCs of LA patients in comparison with non-LA-HIV subjects and, therefore, provided novel insights to the pathogenesis of HIV-associated lipoatrophy. Our study also highlights the potential usage of some of these genes as early markers of future complications.
authors.affiliation: HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR)-Hospital San Pedro, Piqueras 98, 26006, Logroño, Spain. cpperez@riojasalud.es.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.affiliation: Genomics Core Facility, Center for Biomedical Research of La Rioja (CIBIR), Piqueras 98, 26006, Logroño, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Iñiguez
authors.affiliation: HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR)-Hospital San Pedro, Piqueras 98, 26006, Logroño, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Recio-Fernández
authors.affiliation: HIV and Associated Metabolic Alterations Unit, Infectious Diseases Department, Center for Biomedical Research of La Rioja (CIBIR)-Hospital San Pedro, Piqueras 98, 26006, Logroño, Spain.
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Oteo
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D063990:Gene Ontology; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D008060:Lipodystrophy / Q000821:virology*; D008297:Male; D010865:Pilot Projects; D059467:Transcriptome; D015854:Up-Regulation
keywords: Cardiovascular events; HIV-associated lipoatrophy; Inflammation; Massive transcriptome sequencing; PBMCs