Comparison of dorsocervical with abdominal subcutaneous adipose tissue in patients with and without antiretroviral therapy-associated lipodystrophy.

Abstract

OBJECTIVE:

Combination antiretroviral therapy (cART) is associated with lipodystrophy, i.e., loss of subcutaneous adipose tissue in the abdomen, limbs, and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulate in this region (buffalo hump). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1-infected cART-treated patients with (cART+LD+) and without (cART+LD-) lipodystrophy.

RESEARCH DESIGN AND METHODS:

We used histology, microarray, PCR, and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n=21) and cART+LD- (n=11).

RESULTS:

Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA; copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD-. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical versus abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot.

CONCLUSIONS:

Because mtDNA is depleted even in the nonatrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal subcutaneous adipose tissue is in expression of homeobox genes.

• Authors: Ksenia Sevastianova, Jussi Sutinen, Dario Greco, Meline Sievers, Kaisa Salmenkivi, Julia Perttilä, Vesa M Olkkonen, Dick Wågsäter, Martin E Lidell, Sven Enerbäck, Per Eriksson, Ulrich A Walker, Petri Auvinen, Matti Ristola, Hannele Yki-Järvinen
• Journal: Diabetes (Diabetes) Vol. 60 Issue 7 Pg. 1894-900 (Jul 2011) ISSN: 1939-327X [Electronic] United States
• PMID: 21602514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 by the American Diabetes Association.

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD68 antigen, human
• DNA, Mitochondrial

Topics

• Adult
• Antigens, CD (biosynthesis)
• Antigens, Differentiation, Myelomonocytic (biosynthesis)
• Antiretroviral Therapy, Highly Active (adverse effects)
• Back
• Body Composition
• DNA, Mitochondrial (genetics)
• Female
• HIV-Associated Lipodystrophy Syndrome (chemically induced, pathology)
• Humans
• Lipodystrophy
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Subcutaneous Fat (pathology)
• Subcutaneous Fat, Abdominal (pathology)