In vitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic disease: a pilot study
| Autor: | Weimian He, Pablo Tebas, Joseph Quinn, Ian Frank, Larisa Zifchak, Sumit Vaghani, Roy J. Kim |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Abdominal Fat Adipose tissue Pilot Projects Biology Article chemistry.chemical_compound In vivo Internal medicine Adipocyte medicine Adipocytes Humans Insulin Insulin-Like Growth Factor I Lipoatrophy Cells Cultured Adiposity Mecasermin Cell Death HIV-Associated Lipodystrophy Syndrome General Medicine Middle Aged medicine.disease Recombinant Proteins Endocrinology Insulin-Like Growth Factor Binding Protein 3 chemistry Body Composition Intercellular Signaling Peptides and Proteins Ritonavir Female Lipodystrophy medicine.drug |
| Zdroj: | Archives of medical research. 44(5) |
| ISSN: | 1873-5487 |
| Popis: | Background and Aims We tested the effects of recombinant insulin-like growth factor-I (IGF-I) in an adipocyte model of HIV lipodystrophy and in an open label study on body composition and metabolism in patients with HIV lipodystrophy. Methods The effects of IGF-I on ritonavir-induced adipocyte cell death were studied in vitro . We assessed lipid accumulation, IGF signaling, apoptosis, and gene expression. We conducted a 24-week open label trial of recombinant IGF-I in ten adults with HIV associated lipoatrophy. Laboratory assessments included glucose, insulin, lipids, and IGF-I. At weeks 0 and 24, body composition studies were performed including skinfold measurement, dual-energy x-ray absorptiometry, and computed tomography of the abdomen and thigh. Results In vitro , ritonavir increased delipidation and apoptosis of adipocytes, whereas co-treatment with IGF-I attenuated the effect. In the clinical study, subcutaneous adipose tissue did not increase in patients after treatment with IGF-I; however, there was a decrease in the proportion of abdominal fat (39.8 ± 7% vs. 34.6 ± 7%, p = 0.007). IGF-I levels increased with treatment (143 ± 28 μg/L at week 0 vs. 453 ± 212 μg/L at week 24, p = 0.002), whereas IGFBP-3 levels declined (3.554 ± 1.146 mg/L vs. 3.235 ± 1.151 mg/L, p = 0.02). Insulin at week 12 decreased significantly (90.1 ± 39.8 pmol/L vs. 33.2 ± 19.6 pmol/L, p = 0.002). There was a nonsignificant decrease in visceral adipose tissue (155.2 ± 68 cm 2 at week 0 vs. 140.6 ± 70 cm 2 at week 24, p = 0.08). Conclusions Use of recombinant IGF-I may lower fasting insulin and abdominal fat in patients with lipoatrophy associated with HIV infection. Further evaluation of this agent for treatment of HIV-associated lipodystrophy may be warranted. |
| Databáze: | OpenAIRE |
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