Licarin B from Myristica fragrans improves insulin sensitivity via PPARγ and activation of GLUT4 in the IRS-1/PI3K/AKT pathway in 3T3-L1 adipocytes

Shyni, G. L.; Kavitha, Sasidharan; Francis, Sajin K.; Das, Arya A.; Nair, Mangalam S.; Raghu, K.

doi:10.1039/c6ra13055k

Cited by 21 publications

(10 citation statements)

References 37 publications

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“…Morita et al found that myristicin protected rats against liver damage caused by lipopolysaccharides and d-galactosamine [ 63 ], but its effect on liver lipid metabolism needs to be further verified. Shyni et al determined that licarin B improved insulin sensitivity via PPARγ and activation of glucose transporter 4(GLUT4) in the IRS-1/PI3K/AKT (insulin receptor substrate-1/phosphoinositide 3-kinase/protein kinase B) pathway in 3T3-L1 adipocytes [ 64 ]. Elemicin is an important alkaloid, widely used as a spice and raw material, and can be used in the synthesis of mescaline, confectionery, condiments, non-alcoholic beverages, etc.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect of Myristica fragrans Houtt. Extracts Against Obesity and Inflammation by Regulating Free Fatty Acids Metabolism in Nonalcoholic Fatty Liver Disease

Zhao

Song

et al. 2020

Nutrients

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Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by the excess accumulation of fat in the hepatocytes. It is commonly associated with severe obesity and inflammation. Free fatty acids (FFAs) are the key to regulate lipid metabolism and immune response in hepatocyte cells. This study examined the effects of AEN (alcohol extract of nutmeg, the seed of Myristica fragrans Houtt.) on the inhibition of lipid synthesis and inflammation in vitro and in vivo and on high-fat diet-induced obesity in NAFLD mice. Our results showed that AEN treatment could downregulate the expression of lipid synthesis-related genes fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c) and lower the lipid content of cells. AEN also inhibited FFAs-mediated inflammation-related cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) expression in cells. In a mouse model, AEN reduced the bodyweight of obese mice and improved NAFLD without affecting food intake. Further analysis revealed that AEN significantly reduced inflammation level, cholesterol and lipid accumulation, blood glucose, and other liver function indexes in mice fed with a high-fat diet. In conclusion, AEN inhibited the aggravation of obesity and inflammation by downregulating lipid-gene expression in the liver to ameliorate NAFLD.

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Section: Discussionmentioning

confidence: 99%

The Protective Effect of Myristica fragrans Houtt. Extracts Against Obesity and Inflammation by Regulating Free Fatty Acids Metabolism in Nonalcoholic Fatty Liver Disease

Zhao

Song

et al. 2020

Nutrients

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“…Western blot analysis was performed following the manufacturer’s instruction and previous studies [7]. After dexamethasone treatment, 3T3-L1 adipocytes were washed twice with ice-cold PBS and lysed in 100 μL RIPA buffer (Beyotime, Nanjing, China).…”

Section: Methodsmentioning

confidence: 99%

“…Dexamethasone is a glucocorticoid analog, and often exacerbates diabetic symptoms [3,4], which has been supported by both clinical studies and studies in animals or cultured cells [4,5]. Dexamethasone may inhibit the translocation of GLUT4 to the cell membrane [6,7,8] to blunt the insulin-induced glucose uptake in the target tissue [9].…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver

Luan

et al. 2019

Molecules

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Dexamethasone is a glucocorticoid analog, which is reported to induce insulin resistance and to exacerbate diabetic symptoms. In this study, we investigated the association between mitochondrial dysfunction and the pathophysiology of dexamethasone-induced insulin resistance. An insulin resistance model in 3T3-L1 adipocyte was established by 48-h treatment of 1 μM dexamethasone, followed with the detection of mitochondrial function. Results showed that dexamethasone impaired insulin-induced glucose uptake and caused mitochondrial dysfunction. Abnormality in mitochondrial function was supported by decreased intracellular ATP and mitochondrial membrane potential (MMP), increased intracellular and mitochondrial reactive oxygen species (ROS) and mtDNA damage. Mitochondrial dynamic changes and biogenesis were suggested by decreased Drp1, increased Mfn2, and decreased PGC-1, NRF1, and TFam, respectively. The mitochondrial DNA (mtDNA) copy number exhibited no change while the mitochondrial mass increased. In agreement, studies in isolated mitochondria from mouse liver also showed dexamethasone-induced reduction of mitochondrial respiratory function, as suggested by decreased mitochondrial respiration controlling rate (RCR), lower MMP, declined ATP synthesis, opening of the mitochondrial permeability transition pore (mPTP), damage of mtDNA, and the accumulation of ROS. In summary, our study suggests that mitochondrial dysfunction occurs along with dexamethasone-induced insulin resistance in 3T3 L1 adipocytes and might be a potential mechanism of dexamethasone-induced insulin resistance.

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“…Cell lysates were centrifuged at 12 000 rpm for 20 min at 4 °C. 25 The protein content of the supernatant was measured using the BCA assay reagent kit. Cell lysates were separated by SDS-PAGE gel electrophoresis and transferred onto a PVDF membrane using a Bio-RAD electrophoresis equipment.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Flavonoid Glycosides from Fenugreek Seeds Regulate Glycolipid Metabolism by Improving Mitochondrial Function in 3T3-L1 Adipocytes in Vitro

Luan

Wang

et al. 2018

J. Agric. Food Chem.

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Fenugreek is a well known annual herb widely used in both medicine and food. Four flavonoid glycosides have been separated from fenugreek seeds in our previous study. In this study, the effects of the four flavonoid glycosides on regulating glycolipid metabolism and improving mitochondrial function were investigated. Isoorientin showed a very significant activity among these flavonoid glycosides. First, isoorientin decreased the accumulation of lipid droplets in 3T3-L1 preadipocytes by reducing the expression of adipokines including PPARγ, C/EBPα, and FAS. Second, isoorientin restored insulin-stimulated glucose uptake in dexamethasone-induced insulin-resistant 3T3-L1 adipocytes by reactivating Akt and AMPK. Finally, isoorientin improved mitochondrial dysfunction induced by dexamethasone in 3T3-L1 adipocytes. Isoorientin also reversed dexamethasone-induced decrease in mitochondrial membrane potential (MMP) and intracellular ATP production, reduced accumulation of intracellular reactive oxygen species (ROS), and protected mitochondrial DNA (mtDNA) from oxidative damage. At the same time, mitochondrial biogenesis is promoted. Therefore, isoorientin may be an attractive candidate as a glucose-lowering and insulin-resistance-improving agent for the treatment of diabetes.

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Licarin B from Myristica fragrans improves insulin sensitivity via PPARγ and activation of GLUT4 in the IRS-1/PI3K/AKT pathway in 3T3-L1 adipocytes

Abstract: Licarin B, a major bioactive compound isolated fromMyristica fragransmace improves glucose uptakeviaPPARγ and GLUT4 translocation in IRS-1/PI3K/AKT pathway in adipocytes

Cited by 21 publications

References 37 publications

The Protective Effect of Myristica fragrans Houtt. Extracts Against Obesity and Inflammation by Regulating Free Fatty Acids Metabolism in Nonalcoholic Fatty Liver Disease

The Protective Effect of Myristica fragrans Houtt. Extracts Against Obesity and Inflammation by Regulating Free Fatty Acids Metabolism in Nonalcoholic Fatty Liver Disease

Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver

Flavonoid Glycosides from Fenugreek Seeds Regulate Glycolipid Metabolism by Improving Mitochondrial Function in 3T3-L1 Adipocytes in Vitro

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