Nonalcoholic Fatty Liver: A Possible New Target for Type 2 Diabetes Prevention and Treatment

Fruci, Barbara; Giuliano, Stefania; Mazza, Angela; Malaguarnera, Roberta; Belfiore, Antonino

doi:10.3390/ijms141122933

Cited by 97 publications

(73 citation statements)

References 184 publications

(196 reference statements)

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“…In this context, it has be hypothesized that NAFLD may be considered as a new target for T2DM prevention and treatment [9] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Scheen

2014

Clin Pharmacokinet

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SUMMARYPatients with type 2 diabetes have an increased risk of chronic liver disease such as nonalcoholic fatty liver disease and steatohepatitis, and about one third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarizes the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and -Obese patients with type 2 diabetes often have non-alcoholic fatty liver disease or steatohepatitis and the use of incretin-based therapies appears mostly favourable in these patients regarding both efficacy and safety.-There is no reported clinical experience with the use of either DPP-4 inhibitors or GLP-1 receptor agonists in diabetic patients with moderate to severe hepatic impairment, so that caution is required in patients with advanced cirrhosis.

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“…In this context, it has be hypothesized that NAFLD may be considered as a new target for T2DM prevention and treatment [9] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Scheen

2014

Clin Pharmacokinet

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“…Therefore, the fermentation-induced changes in anthocyanin composition appear to change how the anthocyanins alter glucose metabolism in estrogen-deficient animals. Hepatic steatosis may be associated with oxidative hepatocellular damage, inflammation, activation of fibrogenesis, and systemic insulin resistance (Fruci et al 2013). The present study found that BCAO decreased hepatic fat storage mainly by increasing fatty acid oxidation and decreasing lipogenesis.…”

Section: Discussionmentioning

confidence: 99%

Cyanidin and malvidin in aqueous extracts of black carrots fermented with Aspergillus oryzae prevent the impairment of energy, lipid and glucose metabolism in estrogen-deficient rats by AMPK activation

Park

Kang²,

Jeong³

et al. 2015

Genes Nutr

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Black carrots (Daucus carota L.) are rich in anthocyanins which contribute many health benefits, but are limited by bioavailability and instability when exposed to oxygen, heat and light. Fermenting black carrots may improve the stability, absorption and bioactivity of its anthocyanins. Here, we examined whether and by what mechanisms the long-term consumption of unfermented black carrot extract (BC) and its extracts fermented with Lactobacillus plantarum (BCLP) or Aspergillus oryzae (BCAO) might prevent menopausal symptoms including impaired energy, glucose and lipid metabolism in estrogen-deficient animals with diet-induced obesity. Ovariectomized (OVX) rats were fed four different high-fat diets containing 2 % dextrin (OVX-control), 2 % BC, 2 % BCLP, or 2 % BCAO for 12 weeks. Sham rats were fed high-fat diets containing 2 % dextrin. The contents of total anthocyanins increased in BCAO compared to BC and BCLP, whereas the contents of cyanidin-3-rutinosides, malvidin-3,5-diglycosides and delphine-3-glucoside were lower and cyanidin and malvidin were much higher in BCLP and BCAO than BC. Fat mass and weight gain were lower in descending order of OVX-control [ BC and BCLP [ BCAO due to increased energy expenditure and fat oxidation. However, BC, BCLP and especially BCAO all normalized HOMA-IR, an indicator of insulin resistance and glucose intolerance, in OVX rats. OVX increased serum total and LDL cholesterol and triglycerides, but BC, BCLP and BCAO significantly prevented the increases. BCAO markedly decreased hepatic triglyceride levels by increasing gene expressions of CPT-1 and PPAR-a, which are involved in fatty acid oxidation, and decreasing mRNA expressions of FAS and SREBP-1c, which are associated with fatty acid synthesis. This was related to increased pAMPK ? pACC signaling and improved hepatic insulin signaling (pAkt ? pFOXO-1). Cyanidin and malvidin markedly decreased fat accumulation in 3T3-L1 adipocytes by increasing CPT-1 and decreasing FAS and SREBP-1c expression in comparison with cyanidin-3-rutinoside and malvidin-3,5-diglycosides. In conclusion, with increasing cyanidin and malvidin, BCAO prevented the exacerbation of lipid and glucose metabolism by activating hepatic insulin signaling and AMPK activation by in OVX rats.

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“…Metformin is used in the treatment of type 2 diabetes and has been investigated for other diseases in which insulin resistance might be an important factor, such as NAFLD [26] . In the present study, we used metformin as a positive control drug during the experiment.…”

Section: Discussionmentioning

confidence: 99%

Alpha-lipoic acid attenuates insulin resistance and improves glucose metabolism in high fat diet-fed mice

Yang

Liu

et al. 2014

Acta Pharmacol Sin

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Aim: To investigate whether alpha-lipoic acid (ALA) could attenuate the insulin resistance and metabolic disorders in high fat diet-fed mice. Methods: Male mice were fed a high fat diet (HFD) plus ALA (100 and 200 mg·kg -1 ·d -1 ) or HFD plus a positive control drug metformin (300 mg·kg ) for 24 weeks. During the treatments, the relevant physiological and metabolic parameters of the mice were measured. After the mice were euthanized, blood samples and livers were collected. The expression of proteins and genes related to glucose metabolism in livers were analyzed by immunoblotting and real time-PCR. Results: HFD induced non-alcoholic fatty liver disease (NAFLD) and abnormal physiological and metabolic parameters in the mice, which were dose-dependently attenuated by ALA. ALA also significantly reduced HFD-induced hyperglycemia and insulin resistance in HFD-fed mice. Furthermore, ALA significantly upregulated the glycolytic enzymes GCK, HK-1 and PK, and the glycogen synthesis enzyme GS, and downregulated the gluconeogenic enzymes PEPCK and G6Pase, thus decreased glucose production, and promoted glycogen synthesis and glucose utilization in livers. Moreover, ALA markedly increased PKB/Akt and GSK3β phosphorylation, and nuclear carbohydrate response element binding protein (ChREBP) expression in livers. Metformin produced similar effects as ALA in HFD-fed mice. Conclusion: ALA is able to sustain glucose homeostasis and prevent the development of NAFLD in HFD-fed mice.

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Nonalcoholic Fatty Liver: A Possible New Target for Type 2 Diabetes Prevention and Treatment

Cited by 97 publications

References 184 publications

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

Cyanidin and malvidin in aqueous extracts of black carrots fermented with Aspergillus oryzae prevent the impairment of energy, lipid and glucose metabolism in estrogen-deficient rats by AMPK activation

Alpha-lipoic acid attenuates insulin resistance and improves glucose metabolism in high fat diet-fed mice

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