BACKGROUND: Sirtuins may provide novel targets for treating some diseases associated with oxidative stress, such as obesity and its comorbidities. However, there are a few in vivo studies in humans about the potential role of sirtuins as therapeutic targets among obese patients undergoing caloric restriction. Therefore, the aim of this study was to assess if the gene expression of sirtuins is modulated in peripheral blood mononuclear cells (PBMC) by a hypocaloric diet devised to lose weight in humans. MATERIALS AND METHODS: Gene expression of two sirtuins (SIRT1 and SIRT2) in the PBMC of obese subjects (32.3 +/- 5.5 kg m(-2)) before and following an 8-week hypocaloric diet was investigated. NADH-coenzyme Q reductase (NDUFS2) and cytochrome c oxidase assembly protein (COX15) gene expression was selected together with plasma antioxidant power and nitric oxide as markers of antioxidant status. A quantitative real-time polymerase chain reaction approach was performed to assess the nutrigenomics outcome. Moreover, 2-keto[1-(13)C]isocaproate breath test (KICA-BT) parameters were evaluated to study mitochondrial oxidation in vivo. RESULTS: The intervention up-regulated the expression of both sirtuins, being inversely associated with total antioxidant capacity and directly related to nitric oxide, mitochondrial oxidation assessed by the KICA-BT and the expression of the mitochondrial proteins COX15 and NDUFS2. CONCLUSION: SIRT1 and SIRT2 may serve as key regulators for some obesity comorbidities related to antioxidant status, while PBMC could be a model to study the effect of the sirtuin response in obesity therapy.
BACKGROUND: Sirtuins may provide novel targets for treating some diseases associated with oxidative stress, such as obesity and its comorbidities. However, there are a few in vivo studies in humans about the potential role of sirtuins as therapeutic targets among obesepatients undergoing caloric restriction. Therefore, the aim of this study was to assess if the gene expression of sirtuins is modulated in peripheral blood mononuclear cells (PBMC) by a hypocaloric diet devised to lose weight in humans. MATERIALS AND METHODS: Gene expression of two sirtuins (SIRT1 and SIRT2) in the PBMC of obese subjects (32.3 +/- 5.5 kg m(-2)) before and following an 8-week hypocaloric diet was investigated. NADH-coenzyme Q reductase (NDUFS2) and cytochrome c oxidase assembly protein (COX15) gene expression was selected together with plasma antioxidant power and nitric oxide as markers of antioxidant status. A quantitative real-time polymerase chain reaction approach was performed to assess the nutrigenomics outcome. Moreover, 2-keto[1-(13)C]isocaproate breath test (KICA-BT) parameters were evaluated to study mitochondrial oxidation in vivo. RESULTS: The intervention up-regulated the expression of both sirtuins, being inversely associated with total antioxidant capacity and directly related to nitric oxide, mitochondrial oxidation assessed by the KICA-BT and the expression of the mitochondrial proteins COX15 and NDUFS2. CONCLUSION:SIRT1 and SIRT2 may serve as key regulators for some obesity comorbidities related to antioxidant status, while PBMC could be a model to study the effect of the sirtuin response in obesity therapy.
Authors: Saula Vigili de Kreutzenberg; Giulio Ceolotto; Italia Papparella; Alessia Bortoluzzi; Andrea Semplicini; Chiara Dalla Man; Claudio Cobelli; Gian Paolo Fadini; Angelo Avogaro Journal: Diabetes Date: 2010-01-12 Impact factor: 9.461