Differential gene expression indicates that 'buffalo hump' is a distinct adipose tissue disturbance in HIV-1-associated lipodystrophy.
OBJECTIVE
To elucidate the molecular basis of the progressive enlargement of dorso-cervical adipose tissue, the so-called 'buffalo hump', that appears in a sub-set of patients with HIV-1/HAART-associated lipodystrophy.


METHODS
Analysis of the expression of marker genes of mitochondrial function, adipogenesis, inflammation and cell proliferation in ten 'buffalo hump' samples and ten subcutaneous fat samples from HIV-1-infected/HAART-treated patients, and in ten healthy controls.


METHODS
Quantitative real-time polymerase chain reaction analysis of mitochondrial DNA and gene transcripts, and immunoblot for specific proteins.


RESULTS
'Buffalo hump' patients had lower levels of mitochondrial DNA and mitochondrial DNA-encoded transcripts with respect to healthy controls. The uncoupling protein (UCP)-1 gene was expressed only in 'buffalo hump' fat. There were no significant changes in the expression of UCP2, UCP3 or of marker genes of adipogenesis in 'buffalo hump' patients relative to healthy controls. 'Buffalo hump' fat did not show the high expression of tumor necrosis factor-alpha and beta2-microglobulin identified in lipoatrophic subcutaneous fat from patients. The expression of the macrophage marker CD68 was also lower in 'buffalo hump' than in subcutaneous fat from patients. In contrast, 'buffalo hump' showed a higher expression of the cell proliferation marker PCNA.


CONCLUSIONS
'Buffalo hump' adipose tissue shows specific disturbances in gene expression with respect to subcutaneous fat from HIV-1-infected/HAART-treated patients. Mitochondrial alterations cannot explain the differential behavior of 'buffalo hump' with respect to adipose depots prone to lipoatrophy. The absence of a local inflammatory status in 'buffalo hump' may explain in part the differential behavior of this adipose tissue.
Guallar
Jordi P
JP
Department of Biochemistry and Molecular Biology and Institut de Biomedicina (IBUB), University of Barcelona, and CIBER Fisiopatología de Obesidad y Nutrición, Instituto de Salud Carlos III, Barcelona, Spain.
Gallego-Escuredo
José M
JM
Domingo
Joan C
JC
Alegre
Marta
M
Fontdevila
Joan
J
Martínez
Esteban
E
Hammond
Emma L
EL
Domingo
Pere
P
Giralt
Marta
M
Villarroya
Francesc
F
D050156:Adipogenesis / Q000235:genetics; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation; D004272:DNA, Mitochondrial / Q000032:analysis; D005260:Female; D015967:Gene Expression Regulation, Viral; D005819:Genetic Markers / Q000235:genetics; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007249:Inflammation / Q000235:genetics; D008068:Lipomatosis / Q000235:genetics* / Q000821:virology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050151:Subcutaneous Fat / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D019380:Anti-HIV Agents; D015415:Biomarkers; D004272:DNA, Mitochondrial; D005819:Genetic Markers; D018809:Proliferating Cell Nuclear Antigen; D014409:Tumor Necrosis Factor-alpha