Expression of adipogenic transcription factors, peroxisome proliferator-activated receptor gamma co-activator 1, IL-6 and CD45 in subcutaneous adipose tissue in lipodystrophy associated with highly active antiretroviral therapy

Kannisto, Katja; Sutinen, Jussi; Korsheninnikova, Elena; Fisher, Rachel M.; Ehrenborg, Ewa; Gertow, Karl; Virkamäki, Antti; Nyman, Tuulikki; Vidal, Hubert; Hamsten, Anders; Yki‐Järvinen, Hannele

doi:10.1097/00002030-200308150-00004

Cited by 108 publications

(109 citation statements)

References 58 publications

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“…Atrophic adipose tissue contains poorly developed adipocytes and a marked alteration in gene expression [10]. It is likely that lipoatrophy leads to reduced gene expression of adiponectin.…”

Section: Discussionmentioning

confidence: 99%

In treatment-naïve and antiretroviral-treated subjects with HIV, reduced plasma adiponectin is associated with a reduced fractional clearance rate of VLDL, IDL and LDL apolipoprotein B-100

Shahmanesh

Stolinski

et al. 2006

Diabetologia

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Aims/hypothesis: We hypothesised that loss of peripheral fat in HIV patients would result in decreased plasma adipocytokines, in particular adiponectin, and that this decrease would be associated with changes in VLDL, IDL and LDL apolipoprotein B kinetics. Methods: Plasma adiponectin, leptin and other cytokines were measured in uninfected control subjects (n=12) and three HIV-positive groups comprising treatment-naïve patients (n=15) and patients on triple antiretroviral therapy containing protease inhibitors (PI, n=15) or non-nucleoside reverse transcriptase inhibitors (NNRTI, n=25). VLDL, IDL and LDL apolipoprotein B kinetics were measured with an infusion of [1− 13 C] leucine. Regional body fat was measured with a dual energy X-ray absorptiometry scan. Insulin resistance was calculated using homeostasis model assessment (HOMA). Results: Adiponectin (median [interquartile range]) was reduced in the treatmentnaive (5.4 μg/ml [4.7-8.5]), PI (5.0 μg/ml [3.3-6.4]) and NNRTI (5.0 μg/ml [3.1-6.7]) groups compared with controls (9.7 μg/ml [6.9-13.3]) (p<0.05). In all subjects adiponectin correlated positively with HDL-cholesterol levels, the VLDL, IDL and LDL apolipoprotein B fractional clearance rates, and with the limb fat:lean body mass ratio (all p<0.01). Adiponectin correlated negatively with plasma triglyceride levels and HOMA (p<0.001).In a linear regression model that included HOMA, adiponectin was an independent predictor of VLDL and HDL-cholesterol levels and the IDL fractional clearance rate. TNF was higher in treatment-naive and PI subjects, and soluble TNF receptor superfamily, members 1A and 1B (previously known as TNF receptors 1 and 2) was higher in PI patients than in control subjects (p<0.05). Conclusions/interpretation: Adiponectin levels are significantly reduced in treated and untreated HIV patients and are predictive of VLDL and IDL apolipoprotein B fractional clearance rates. Adiponectin may have a direct effect on lipoprotein metabolism, which may be independent of insulin.

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Section: Discussionmentioning

confidence: 99%

In treatment-naïve and antiretroviral-treated subjects with HIV, reduced plasma adiponectin is associated with a reduced fractional clearance rate of VLDL, IDL and LDL apolipoprotein B-100

Shahmanesh

Stolinski

et al. 2006

Diabetologia

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“…Isolated RNA was stored at Ϫ80°C until quantification of the target mRNAs. A total of 0.1 g of RNA was transcribed into cDNA using Moloney murine leukemia virus reverse transcriptase (Life Technologies, Paisley, UK) and oligo(dT) [12][13][14][15][16][17][18] primers.…”

Section: Methodsmentioning

confidence: 99%

Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy

Sevastianova

Sutinen²,

Kannisto³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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“…Body fat was measured by dual-energy x-ray absorptiometry as described [28]. Subcutaneous and intra-abdominal fat was measured by magnetic resonance imaging of 16 transaxial scans reaching from 8 cm above to 8 cm below the fourth and fifth lumbar interspace as described [23].…”

Section: Methodsmentioning

confidence: 99%

“…Subcutaneous abdominal adipose tissue biopsies taken by needle aspiration under local anaesthesia were homogenised in 2 ml RNA STAT-60 (Tel-Test, Friendswood, Tex., USA) and total RNA was isolated as described [23]. For cDNA synthesis we used 100 ng total RNA with M-MLV reverse transcriptase (Life Technologies, Paisley, UK).…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies of human adipose tissue have shown ALBP and KLBP expression to be increased after weight loss in obese subjects and CD36 expression to be decreased [22]. Moreover, lipodystrophy (which is strongly related to insulin resistance) in HIV-positive patients undergoing highly active antiretroviral therapy was associated with reduced adipose tissue ACS1 expression [23]. In addition, FATP1 mRNA levels in skeletal muscle were negatively correlated with BMI in middle-aged women (but not in men), whereas no such correlation was observed for adipose tissue FATP1 expression, which was analysed in men only [24].…”

Section: Introductionmentioning

confidence: 92%

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Expression of fatty-acid-handling proteins in human adipose tissue in relation to obesity and insulin resistance

et al. 2004

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Aims/hypothesis. Protein-mediated trans-membrane and intracellular fatty acid trafficking are becoming increasingly recognised as biochemically and physiologically important concepts. Obesity and insulin resistance are polygenic disorders, heavily influenced by environmental and life-style factors, and are virtually always associated with disturbed fatty acid metabolism in adipose and other tissues. The aim of this study was to investigate mRNA expression levels of fatty-acid-handling proteins in adipose tissue in relation to markers of genetic and acquired obesity and insulin resistance. Methods. We quantified mRNA expression of subcutaneous adipose tissue fatty-acid-handling proteins (ALBP, KLBP, FATP1, FATP4, CD36, ACS1) in 17 monozygotic twin-pairs with a range of intra-pair differences (∆) in BMI and detailed measures of obesity and insulin resistance, allowing influences of genetic and non-genetic factors to be distinguished. Results. In acquired obesity FATP4 expression was up-regulated independently of genetic background (∆FATP4 versus ∆BMI; r=0.50, p=0.04; ∆FATP4 versus ∆body fat; r=0.59, p=0.01). Similarly, CD36 and FATP1 expression correlated with acquired differences in HDL cholesterol and non-esterified fatty acid concentrations respectively. Moreover, FATP4 and CD36 expression levels correlated with measures of obesity and insulin resistance that are influenced by both genetic and non-genetic factors (FATP4 versus BMI: r=0.53, p=0.0001; FATP4 versus body fat: r=0.51, p=0.002; FATP4 versus homeostasis model assessment [HOMA]: r=0.49, p=0.001; CD36 versus BMI: r=0.50, p=0.02; CD36 versus body fat: r=0.63, p=0.001; CD36 versus HOMA: r=0.34, p=0.06). Conclusions/interpretation. These findings indicate that expression of specific adipose tissue fatty-acidhandling proteins is related to obesity and insulin resistance, and that, in particular, FATP4 plays a role in acquired obesity. Our results suggest that facilitated fatty acid trafficking is a physiologically and pathologically relevant phenomenon in man.

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Expression of adipogenic transcription factors, peroxisome proliferator-activated receptor gamma co-activator 1, IL-6 and CD45 in subcutaneous adipose tissue in lipodystrophy associated with highly active antiretroviral therapy

Cited by 108 publications

References 58 publications

In treatment-naïve and antiretroviral-treated subjects with HIV, reduced plasma adiponectin is associated with a reduced fractional clearance rate of VLDL, IDL and LDL apolipoprotein B-100

In treatment-naïve and antiretroviral-treated subjects with HIV, reduced plasma adiponectin is associated with a reduced fractional clearance rate of VLDL, IDL and LDL apolipoprotein B-100

Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy

Expression of fatty-acid-handling proteins in human adipose tissue in relation to obesity and insulin resistance

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