Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways

Yasmin, Tahmina; Rahman, Mizanur; Khan, Ferdous; Kabir, Fariha; Lasker, Shoumen; Islam, M.D.; Hossain, Mohammad Maqsud; Hasan, Raquibul; Rana, Sohel; Alam, Ashraful

doi:10.1016/j.bbrep.2021.101168

Cited by 15 publications

(9 citation statements)

References 61 publications

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“…Palmitate, for example, as a saturated fatty acid, promotes cytokines secretion as IL-6 and TNF-α that can lead to insulin resistance and glucose intolerance [ 30 ]. Meanwhile, HFD downregulates the expression of GLUT4, which induces glucose intolerance [ 31 ]. It has been reported that the activated AMP protein kinase (AMPK) plays a significant role in regulating cellular energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model

et al. 2023

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Background: Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFD/STZ)-induced mice model of type 2 diabetes. Materials and Methods: Mice were fed with HFD followed by two consecutive low doses of STZ (40 mg/kg). HFD/STZ diabetic mice were treated orally with isorhamnetin (10 mg/kg) or (200 mg/kg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. Results: Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group (p < 0.001). Isorhamnetin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control mice (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in diabetic mice treated with isorhamnetin compared to the vehicle controls. Fasting glucose level was significantly lower in diabetic mice treated with isorhamnetin during the intraperitoneal glucose tolerance test (IPGTT) (p < 0.001). The skeletal muscle protein contents of GLUT4 and p-AMPK-α were upregulated following treatment with isorhamnetin (p > 0.01). LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with isorhamnetin compared to vehicle control (p < 0.001). Isorhamnetin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.05) in diabetic mice compared to vehicle control. Conclusions: Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D.

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Section: Discussionmentioning

confidence: 99%

Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model

et al. 2023

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“…Metformin reduces lipogenesis through lipogenic enzyme inhibition and promotes fatty acid oxidation, thereby reducing triglycerides, cholesterol, and fatty liver. Metformin treatment has been shown to reduce HF diet-induced changes in the fatty liver in pregnant and non-pregnant rodents [29,30]. In humans, the therapeutic effect of metformin on the fatty liver has not been as dramatic as that observed in rodent studies, as indicated by liver histology.…”

Section: Discussionmentioning

confidence: 99%

Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications

Huang

Tiao

Lin

et al. 2022

IJMS

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Maternal high-fat (HF) diet exposure in utero may affect fetal development and cause metabolic problems throughout life due to lipid dysmetabolism and oxidative damage. Metformin has been suggested as a potential treatment for body weight reduction and nonalcoholic fatty liver disease, but its reprogramming effect on offspring is undetermined. This study assesses the effects of maternal metformin treatment on hepatic steatosis in offspring caused by maternal HF diet. Female rats were fed either a control or an HF diet before conception, with or without metformin treatment during gestation, and placenta and fetal liver tissues were collected. In another experiment, the offspring were fed a control diet until 120 d (adult stage). Metformin treatment during pregnancy ameliorates placental oxidative stress and enhances placental glucose transporter 1 (GLUT1), GLUT3, and GLUT4 expression levels through 5’ adenosine monophosphate-activated protein kinase (AMPK) activation. Maternal metformin treatment was shown to reprogram maternal HF diet-induced changes in offspring fatty liver with the effects observed in adulthood as well. Further validation is required to develop maternal metformin therapy for clinical applications.

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“…Considering the role of the PPARγ and SREBP-1c signaling pathway in NAS and DIS development, and LIRA hepatoprotective action, analysis of these and other signaling pathways related to it (such as Acyl-CoA Synthetase Long Chain Family Member 1, ACSL1 , which channels fatty acids from fatty acid oxidation to lipid synthesis), could help better understand their effects on hepatocytes [ 13 , 26 , 27 ]. Yasmin et al showed that apart from PPARγ involvement in fatty liver changes in rats, upregulation of C/EBPα (CCAAT Enhancer Binding Protein α) is also responsible for steatosis progression [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Liraglutide Exerts Protective Effects by Downregulation of PPARγ, ACSL1 and SREBP-1c in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis

Kolarić

Kizivat²,

Mihaljevic

et al. 2022

CIMB

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(1) Background: With the aging of the population and polypharmacy encountered in the elderly, drug-induced steatosis (DIS) has become frequent cause of non-alcoholic steatosis (NAS). Indeed, NAS and DIS may co-exist, making the ability to distinguish between the entities ever more important. The aim of our study was to study cell culture models of NAS and DIS and determine the effects of liraglutide (LIRA) in those models. (2) Methods: Huh7 cells were treated with oleic acid (OA), or amiodarone (AMD) to establish models of NAS and DIS, respectively. Cells were treated with LIRA and cell viability was assessed by MTT, lipid accumulation by Oil-Red-O staining and triglyceride assay, and intracellular signals involved in hepatosteatosis were quantitated by RT-PCR. (3) Results: After exposure to various OA and AMD concentrations, those that achieved 80% of cells viabilities were used in further experiments to establish NAS and DIS models using 0.5 mM OA and 20 µM AMD, respectively. In both models, LIRA increased cell viability (p < 0.01). Lipid accumulation was increased in both models, with microsteatotic pattern in DIS, and macrosteatotic pattern in NAS which corresponds to greater triglyceride accumulation in latter. LIRA ameliorated these changes (p < 0.001), and downregulated expression of lipogenic ACSL1, PPARγ, and SREBP-1c pathways in the liver (p < 0.01) (4) Conclusions: LIRA ameliorates hepatocyte steatosis in Huh7 cell culture models of NAS and DIS.

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Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways

Cited by 15 publications

References 61 publications

Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model

Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model

Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications

Liraglutide Exerts Protective Effects by Downregulation of PPARγ, ACSL1 and SREBP-1c in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis

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