Minimal effects of Darunavir on adipocyte differentiation and metabolism in 3T3-L1 cells |
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| Authors: | Patricia Pérez-Matute Laura Pérez-Martínez José Ramón Blanco José Antonio Oteo |
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| Affiliation: | HIV and Associated Metabolic Alterations Unit, Infectious Diseases Area, Center for Biomedical Research of La Rioja (CIBIR), Piqueras, no 98, 26006, Logroño, Spain;HIV and Associated Metabolic Alterations Unit, Infectious Diseases Area, Center for Biomedical Research of La Rioja (CIBIR), Piqueras, no 98, 26006, Logroño, Spain;Infectious Diseases Area, Hospital San Pedro-CIBIR, 26006, Logroño, Spain;Kitasato Institute for Life Science, Department of Research Project Studies, Kitasato University, 5–9–1 Shirokane, Minato-ku, Tokyo 108-0072, Japan;Saiseikai Yokohamashi Tobu Hospital, 3-6-1 Shimosueyoshi, Tsurumi-ku, Yokohama 230-8765, Japan;Hosen College of Childhood Education, 2-33-26 Chuo, Nakano-ku, Tokyo 164-8631, Japan;Tokyo Metropolitan Children’s Medical Center, Musashidai 2-8-29 Fuchu, Tokyo 183-8561, Japan;Nagoya, Japan;Dainippon Sumitomo Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan;Dainippon Sumitomo Pharma Co., Ltd., 6-8 Doshomachi 2-Chome, Chuo-ku, Osaka 541-0045, Japan;Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan;Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Omori-nishi, Ota-ku, Tokyo 1438540, Japan;Department of Urology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, 807-8555, Kitakyushu, Fukuoka, Japan;Department of Urology, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, 470-1192, Toyoake, Aichi, Japan;Department of Urology, Sapporo Medical University School of Medicine, S1W17, Chuo-ku, 060-8556, Sapporo, Hokkaido, Japan;Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, 501-1194, Gifu, Japan;Blood Purification Center, Kagoshima University Hospital, 8-35-1 Sakuragaoka, 890-8532, Kagoshima, Japan;Division of Urology, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan;Kyurin Medical Laboratory, 27-25 Morishita-machi, Yahatanishi-ku, 806-0046, Kitakyushu, Fukuoka, Japan;Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan;Araki Urological Clinic, 390-1 Sasaoki, 710-0834, Kurashiki, Okayama, Japan;Department of Infection Control and Prevention, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan;Department of Urology, Hyogo College of Medicine, 75 Yamauchi-cho, 669-2337, Sasayama, Hyogo, Japan;Research Division for Development of Anti-Infective Agents, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan;Division of Clinical Infectious Diseases and Chemotherapy, Tohoku Pharmaceutical University, Sendai, Japan;Research Division for Development of Anti-Infective Agents, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan;Infection Control Unit, Tonami General Hospital, Tonami, Toyama 939-1395, Japan;Department of Gastroenterology, Tonami General Hospital, Tonami, Toyama 939-1395, Japan;Department of Pediatrics, Tonami General Hospital, Tonami, Toyama 939-1395, Japan;Department of Nephrology, Tonami General Hospital, Tonami, Toyama 939-1395, Japan;Department of Clinical Laboratory, Tonami General Hospital, Tonami, Toyama 939-1395, Japan;Center for Infectious Diseases and Infection Control, Keio University School of Medicine, Tokyo, Japan;Department of Pediatrics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, 160-8582, Tokyo, Japan;Department of Pediatrics Surgery, School of Medicine, Keio University, Tokyo, Japan |
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| Abstract: | Darunavir (DRV) has been confirmed to be an effective option for antiretroviral-naïve and experienced patients. It results in a more favorable lipid and glucose profile than other antiretrovirals. The objective of this study was to investigate the molecular mechanisms that could underline the lack of toxicity of DRV to metabolism and the better profile observed in HIV-infected patients in comparison with other drugs. The effects of DRV on adipogenesis were evaluated by oil red O staining after 8 days of induction of differentiation in 3T3-L1 cells, a very adequate and convenient cell culture model for investigation of adipose function. Several adipogenic genes (C/EBPα, PPARγ, Pref-1, and AP2) were analyzed by real time-PCR. Fully differentiated adipocytes were also incubated with DRV for 24 h and glucose utilization and lactate and glycerol production were quantified by use of an autoanalyzer. No effects of DRV on murine adipocyte differentiation were observed. Significant decreases in lipolysis, glucose uptake, and lactate production were observed at the highest concentration used (50 μM) (p < 0.01–p < 0.001). However, DRV treatment did not modify the percentage of glucose transformed into lactate. Co-treatment with RTV did not induce any further effects on lipolysis and glucose metabolism. This study suggests that the decrease in lipolysis observed after DRV treatment could explain, at least in part, the lower plasma lipids observed in patients under DRV/r treatment in comparison with other drugs. The lack of effects of RTV co-treatment on glucose and lipid metabolism emphasizes the safety of this treatment. |
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| Keywords: | HIV-associated lipodystrophy Darunavir Ritonavir Adipogenesis Lipolysis Glucose metabolism |
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