Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes

The current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1–100 μM) for four...

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Main Authors: Khanyisani Ziqubu, Christo J. F. Muller, Phiwayinkosi V. Dludla, Sinenhlanhla X. H. Mthembu, Nnini Obonye, Johan Louw, Abidemi P. Kappo, Sonia Silvestri, Patrick Orlando, Luca Tiano, Sithandiwe E. Mazibuko-Mbeje
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/8/1773
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author Khanyisani Ziqubu
Christo J. F. Muller
Phiwayinkosi V. Dludla
Sinenhlanhla X. H. Mthembu
Nnini Obonye
Johan Louw
Abidemi P. Kappo
Sonia Silvestri
Patrick Orlando
Luca Tiano
Sithandiwe E. Mazibuko-Mbeje
author_facet Khanyisani Ziqubu
Christo J. F. Muller
Phiwayinkosi V. Dludla
Sinenhlanhla X. H. Mthembu
Nnini Obonye
Johan Louw
Abidemi P. Kappo
Sonia Silvestri
Patrick Orlando
Luca Tiano
Sithandiwe E. Mazibuko-Mbeje
author_sort Khanyisani Ziqubu
collection DOAJ
description The current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1–100 μM) for four hours. Subsequently, the metabolic activity, lipid accumulation, and mitochondrial respiration were assessed. Furthermore, to unravel the molecular mechanisms that might elucidate the bioactivity of isoorientin, protein expression of the genes involved in insulin signaling and energy expenditure, such as AKT and AMPK, were investigated. The results showed that isoorientin, at different doses, could block lipid storage and enhance glycerol release, with a concomitant improvement of the metabolic activity and mitochondrial function. Although the observed beneficial effects of isoorientin on these cultured 3T3-L1 adipocytes were not consistent at all concentrations, it was clear that doses between 1 and 10 μM were most effective compared to the untreated control. Moreover, the activity of isoorientin was comparable to tested positive controls of CL-316,2431, isoproterenol, insulin, and metformin. Mechanistically, protein expression of AKT and AMPK, was enhanced with isoorientin exposure, suggesting their partial role in modulating lipid metabolism and mitochondrial biogenesis. Indeed, our results showed that isoorientin has the ability to enhance mitochondrial respiration, as we observed an increase in the ATP and oxygen consumption rate. Therefore, we concluded that isoorientin has a potential to impact mitochondrial activity, lipid metabolism and energy expenditure using an in vitro experimental model of obesity.
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spelling doaj.art-32a3642d8a194dc5bf4f66f19f041cdc2023-11-19T21:26:22ZengMDPI AGMolecules1420-30492020-04-01258177310.3390/molecules25081773Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated AdipocytesKhanyisani Ziqubu0Christo J. F. Muller1Phiwayinkosi V. Dludla2Sinenhlanhla X. H. Mthembu3Nnini Obonye4Johan Louw5Abidemi P. Kappo6Sonia Silvestri7Patrick Orlando8Luca Tiano9Sithandiwe E. Mazibuko-Mbeje10Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South AfricaBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South AfricaDepartment of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South AfricaDepartment of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, ItalyBiomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South AfricaThe current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1–100 μM) for four hours. Subsequently, the metabolic activity, lipid accumulation, and mitochondrial respiration were assessed. Furthermore, to unravel the molecular mechanisms that might elucidate the bioactivity of isoorientin, protein expression of the genes involved in insulin signaling and energy expenditure, such as AKT and AMPK, were investigated. The results showed that isoorientin, at different doses, could block lipid storage and enhance glycerol release, with a concomitant improvement of the metabolic activity and mitochondrial function. Although the observed beneficial effects of isoorientin on these cultured 3T3-L1 adipocytes were not consistent at all concentrations, it was clear that doses between 1 and 10 μM were most effective compared to the untreated control. Moreover, the activity of isoorientin was comparable to tested positive controls of CL-316,2431, isoproterenol, insulin, and metformin. Mechanistically, protein expression of AKT and AMPK, was enhanced with isoorientin exposure, suggesting their partial role in modulating lipid metabolism and mitochondrial biogenesis. Indeed, our results showed that isoorientin has the ability to enhance mitochondrial respiration, as we observed an increase in the ATP and oxygen consumption rate. Therefore, we concluded that isoorientin has a potential to impact mitochondrial activity, lipid metabolism and energy expenditure using an in vitro experimental model of obesity.https://www.mdpi.com/1420-3049/25/8/1773isoorientinobesitymetabolic activitylipid accumulation3T3-L1 adipocytes
spellingShingle Khanyisani Ziqubu
Christo J. F. Muller
Phiwayinkosi V. Dludla
Sinenhlanhla X. H. Mthembu
Nnini Obonye
Johan Louw
Abidemi P. Kappo
Sonia Silvestri
Patrick Orlando
Luca Tiano
Sithandiwe E. Mazibuko-Mbeje
Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes
Molecules
isoorientin
obesity
metabolic activity
lipid accumulation
3T3-L1 adipocytes
title Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes
title_full Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes
title_fullStr Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes
title_full_unstemmed Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes
title_short Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes
title_sort impact of isoorientin on metabolic activity and lipid accumulation in differentiated adipocytes
topic isoorientin
obesity
metabolic activity
lipid accumulation
3T3-L1 adipocytes
url https://www.mdpi.com/1420-3049/25/8/1773
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