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Increased expression of TNF-alpha, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels.
Am J Physiol Endocrinol Metab 2003; 285(5):E1072-80AJ

Abstract

Human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is a side effect of highly active antiretroviral therapy of HIV-infected patients; however, the mechanism of the lipodystrophy and insulin resistance seen in this syndrome remains elusive. Adiponectin, an adipocyte-specific protein, is thought to play an important role in regulating insulin sensitivity. We investigated circulating levels and gene expression of adiponectin in subcutaneous abdominal adipose tissue (AT) from 18 HIV-infected patients with HALS compared with 18 HIV-infected patients without HALS. Implications of cytokines for adiponectin levels were investigated by determining circulating levels of TNF-alpha, IL-6, and IL-8 as well as gene expression of these cytokines in AT. HALS patients exhibited 40% reduced plasma adiponectin levels (P < 0.05) compared with non-HALS subjects. Correspondingly, adiponectin mRNA levels in AT were reduced by >50% (P = 0.06). HALS patients were insulin resistant, and a positive correlation was found between plasma adiponectin and insulin sensitivity (r = 0.55, P < 0.01) and percent limb fat (r = 0.61, P < 0.01). AT mRNA of TNF-alpha, IL-6, and IL-8 was increased in AT of HALS subjects (P < 0.05), and both AT TNF-alpha mRNA and plasma TNF-alpha were negatively correlated to plasma adiponectin (P < 0.05). Finally, TNF-alpha was found in vitro to inhibit human AT adiponectin mRNA by 80% (P < 0.05). In conclusion, HALS patients have reduced levels of plasma adiponectin and adiponectin mRNA in AT. Increased cytokine mRNA in AT is hypothesized to exert an inhibitory effect on adiponectin gene expression and, consequently, to play a role in the reduced plasma adiponectin levels found in HALS patients.

Authors+Show Affiliations

Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Tage Hansensgade 2, 8000 Aarhus C, Denmark. lihn@dadlnet.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12876073

Citation

Lihn, Aina S., et al. "Increased Expression of TNF-alpha, IL-6, and IL-8 in HALS: Implications for Reduced Adiponectin Expression and Plasma Levels." American Journal of Physiology. Endocrinology and Metabolism, vol. 285, no. 5, 2003, pp. E1072-80.
Lihn AS, Richelsen B, Pedersen SB, et al. Increased expression of TNF-alpha, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels. Am J Physiol Endocrinol Metab. 2003;285(5):E1072-80.
Lihn, A. S., Richelsen, B., Pedersen, S. B., Haugaard, S. B., Rathje, G. S., Madsbad, S., & Andersen, O. (2003). Increased expression of TNF-alpha, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels. American Journal of Physiology. Endocrinology and Metabolism, 285(5), pp. E1072-80.
Lihn AS, et al. Increased Expression of TNF-alpha, IL-6, and IL-8 in HALS: Implications for Reduced Adiponectin Expression and Plasma Levels. Am J Physiol Endocrinol Metab. 2003;285(5):E1072-80. PubMed PMID: 12876073.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased expression of TNF-alpha, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels. AU - Lihn,Aina S, AU - Richelsen,Bjørn, AU - Pedersen,Steen B, AU - Haugaard,Steen B, AU - Rathje,Gulla Søby, AU - Madsbad,Sten, AU - Andersen,Ove, Y1 - 2003/07/22/ PY - 2003/7/24/pubmed PY - 2003/12/3/medline PY - 2003/7/24/entrez SP - E1072 EP - 80 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 285 IS - 5 N2 - Human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) is a side effect of highly active antiretroviral therapy of HIV-infected patients; however, the mechanism of the lipodystrophy and insulin resistance seen in this syndrome remains elusive. Adiponectin, an adipocyte-specific protein, is thought to play an important role in regulating insulin sensitivity. We investigated circulating levels and gene expression of adiponectin in subcutaneous abdominal adipose tissue (AT) from 18 HIV-infected patients with HALS compared with 18 HIV-infected patients without HALS. Implications of cytokines for adiponectin levels were investigated by determining circulating levels of TNF-alpha, IL-6, and IL-8 as well as gene expression of these cytokines in AT. HALS patients exhibited 40% reduced plasma adiponectin levels (P < 0.05) compared with non-HALS subjects. Correspondingly, adiponectin mRNA levels in AT were reduced by >50% (P = 0.06). HALS patients were insulin resistant, and a positive correlation was found between plasma adiponectin and insulin sensitivity (r = 0.55, P < 0.01) and percent limb fat (r = 0.61, P < 0.01). AT mRNA of TNF-alpha, IL-6, and IL-8 was increased in AT of HALS subjects (P < 0.05), and both AT TNF-alpha mRNA and plasma TNF-alpha were negatively correlated to plasma adiponectin (P < 0.05). Finally, TNF-alpha was found in vitro to inhibit human AT adiponectin mRNA by 80% (P < 0.05). In conclusion, HALS patients have reduced levels of plasma adiponectin and adiponectin mRNA in AT. Increased cytokine mRNA in AT is hypothesized to exert an inhibitory effect on adiponectin gene expression and, consequently, to play a role in the reduced plasma adiponectin levels found in HALS patients. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/12876073/Increased_expression_of_TNF_alpha_IL_6_and_IL_8_in_HALS:_implications_for_reduced_adiponectin_expression_and_plasma_levels_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00206.2003?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -