Increased systemic and adipose tissue cytokines in patients with HIV-associated lipodystrophy

Johnson, Julia A.; Albu, Jeanine; Engelson, Ellen S.; Fried, Susan K.; Inada, Yoritaro; Ionescu, Gabriel; Kotler, Donald P.

doi:10.1152/ajpendo.00056.2003

Cited by 125 publications

(116 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We therefore concluded that the circulating evidence for inflammation in the lipodystrophic mice originated in the dystrophic fat. Importantly and consistent with our results, increased levels of expression of proinflammatory cytokines and macrophages (17,18) have been found in s.c. adipose tissue from humans with HIV-associated lipodystrophy, the most common form of lipodystrophy seen today. This data reinforces the relevance of the lipodystrophic mouse model used here to clinical practice.…”

Section: Discussionsupporting

confidence: 92%

“…Inflammation has not been shown to contribute to the dysmetabolic consequences of lipodystrophy, although increases in the expression of proinflammatory cytokines and increased macrophage numbers have been found in the s.c. adipose tissue of patients with HIV-associated lipodystrophy (17,18). We therefore tested whether inflammation is associated with lipodystrophy and its metabolic consequences in aP2-nSREBP-1c transgenic (Tg) mice, an established model of the disease with characteristics that match many of those seen in humans (19).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inflammation and adipose tissue macrophages in lipodystrophic mice

Herrero

Shapiro

Nayer

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

141

108

View full text Add to dashboard Cite

Lipodystrophy and obesity are opposites in terms of a deficiency versus excess of adipose tissue mass, yet these conditions are accompanied by similar metabolic consequences, including insulin resistance, dyslipidemia, hepatic steatosis, and increased risk for diabetes and atherosclerosis. Hepatic and myocellular steatosis likely contribute to metabolic dysregulation in both states. Inflammation and macrophage infiltration into adipose tissue also appear to participate in the pathogenesis of obesity-induced insulin resistance, but their contributions to lipodystrophy-induced insulin resistance have not been evaluated. We used aP2-nSREBP-1c transgenic (Tg) mice, an established model of lipodystrophy, to ask this question. Circulating cytokine elevations suggested systemic inflammation but even more dramatic was the number of infiltrating macrophages in all white and brown adipose tissue depots of the Tg mice; in contrast, there was no evidence of inflammatory infiltrates or responses in any other tissue including liver. Despite there being overt evidence of adipose tissue inflammation, antiinflammatory strategies including salicylate treatment and genetic suppression of myeloid NF-κB signaling that correct insulin resistance in obesity were ineffective in the lipodystrophic mice. We further showed that adipose tissue macrophages (ATMs) in lipodystrophy and obesity are very different in terms of activation state, gene expression patterns, and response to lipopolysaccharide. Although ATMs are even more abundant in lipodystrophy than in obesity, they have distinct phenotypes and likely roles in tissue remodeling, but do not appear to be involved in the pathogenesis of insulin resistance.

show abstract

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Inflammation and adipose tissue macrophages in lipodystrophic mice

Herrero

Shapiro

Nayer

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

141

108

View full text Add to dashboard Cite

show abstract

“…Thus, the low-adiponectin state may be the common defect in both obesity and lipodystrophy. However, increased plasma levels of various proinflammatory cytokines expressed by adipose tissue have also been observed in various groups of lipodystrophic subjects [7][8][9][10][11]. The aim of the present study was to investigate the interrelationships between the abnormalities of adiponectin and other adipokines, and to determine which defects are most closely predictive of the metabolic syndrome in a genetically and phenotypically well-characterised group of subjects with FPLD and unaffected controls.…”

Section: Introductionmentioning

confidence: 97%

Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C

et al. 2005

View full text Add to dashboard Cite

Aims/hypothesis: Familial partial lipodystrophy (FPLD) and obesity are both associated with increased risks of type 2 diabetes and cardiovascular disease. Although adipokines have been implicated, few data exist in subjects with FPLD; therefore we investigated a family with FPLD due to a lamin A/C mutation in order to determine how abnormalities of the plasma adipokine profile relate to insulin resistance and the metabolic syndrome. Methods: Plasma levels of adiponectin, leptin, resistin, IL-1β, IL-6 and TNF-α in 30 subjects (ten patients, 20 controls) were correlated with indices of metabolic syndrome. Results: Compared with controls, FPLD patients had significantly lower plasma levels of adiponectin (3.7±1.0 in FDLP cases vs 7.1±0.72 μg/ml in controls, p=0.02), leptin (1.23±0.4 vs 9.0±1.3 ng/ml, p=0.002) and IL-6 (0.59±0.12 vs 1.04±0.17 pg/ml, p=0.047) and elevated TNF-α (34.8±8.1 vs 13.7±2.7 pg/ml, p=0.028), whereas IL-1β and resistin were unchanged. In both groups, adiponectin levels were inversely correlated with body fat mass (controls, r=−0.44, p=0.036; FDLP, r=−0.67, p=0.025), insulin resistance (controls, r=−0.62, p=0.003; FDLP, r=−0.70, p=0.025) and other features of the metabolic syndrome. TNF-α concentrations were positively related to fat mass (controls, r=0.68, p=0.001; FDLP, r=0.64, p=0.048) and insulin resistance (controls, r=0.86, p=0.001; FDLP, r=0.75, p=0.013). IL-6, IL-1β and resistin did not demonstrate any correlations with the metabolic syndrome in either group. Conclusions/interpretation: Low adiponectin and leptin and high TNF-α were identified as the major plasma adipokine abnormalities in FPLD, consistent with the hypothesis that low adiponectin and high TNF-α production may be mechanistically related, and perhaps responsible for the development of insulin resistance and cardiovascular disease in FPLD.

show abstract

“…High levels of expression of TNFa, and other cytokines such as interleukin-6 or interleukin-18 have been found in subcutaneous adipose tissue from HALS patients 14,64,85 together with similar increases in systemic levels of inflammatory cytokines such as TNFa, interleukins 1, 6, 8 and 18 and interferon-a. [86][87][88] Cytokine levels in blood correlated with viral load according to some studies. 88 Moreover, there is evidence of macrophage infiltration including the presence of lipogranulomas in subcutaneous adipose tissue in HALS.…”

Section: The Paradox Of the Common Inflammation Status In Adipose Tismentioning

confidence: 97%