Insulin resistance by TNF-α is associated with mitochondrial dysfunction in 3T3-L1 adipocytes and is ameliorated by punicic acid, a PPARγ agonist

Anusree, S.S.; Nisha, V. M.; Priyanka, A; Raghu, K.

doi:10.1016/j.mce.2015.06.018

Cited by 58 publications

(55 citation statements)

References 50 publications

(40 reference statements)

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“…Under conditions of positive energy balance, the adipose tissue macrophages not only increase in quantity but also polarize to the M1 type [5]. M1 macrophages are responsible for insulin resistance [6]. Restraining M1 polarization relieved obesity-induced insulin resistance in adipose tissue [7,8].…”

Section: Introductionmentioning

confidence: 99%

Adipocyte-Derived Exosomes Carrying Sonic Hedgehog Mediate M1 Macrophage Polarization-Induced Insulin Resistance via Ptch and PI3K Pathways

Song

Han

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Adipocyte-derived exosomes (ADEs) stimulate the activation of macrophages and contribute to the development of insulin resistance. Sonic Hedgehog (Shh) is an exosome-carrying protein and stimulates macrophages to secrete inflammatory cytokines. However, the impact of ADEs carrying Shh on the pro-inflammatory activation of macrophages and consequently, adipocyte insulin resistance is unclear. Methods: 3T3-L1 adipocytes were cultured with high glucose and insulin to imitate the pathogeny of insulin resistance. ADEs were isolated from conditioned media of 3T3-L1 adipocytes via differential ultracentrifugation. We explored the role of ADEs carrying Shh in the polarization of macrophages by flow cytometry. Western blot and electrophoretic mobility shift assay (EMSA) were performed to determine the activation of Shh-mediated signalling pathways. The effects of ADE-treated macrophages on adipocyte insulin signalling were studied by Western blot. Results: We found that circulating Shh-positive exosomes were increased in type 2 diabetes patients. High glucose and insulin increased the secretion of Shh-positive ADEs. The ADEs carrying Shh induced pro-inflammatory or M1 polarization of bone marrow-derived macrophages (BMDM) and RAW 264.7 macrophages. Inhibitors of Ptch and PI3K blocked the M1 polarization induced by ADEs, which suggests that ADEs carrying Shh mediated M1 macrophage polarization through the Ptch/PI3K signalling pathway. ADE-treated RAW 264.7 macrophages were subsequently used to assess the effect on insulin signalling in adipocytes. Using a co-culture assay, we showed that both ADE-treated macrophages and exosomes from these macrophages could decrease the expression of insulin-resistant substrate-1 (IRS-1) and hormone-sensitive lipase (HSL) in adipocytes. Inhibitors of Ptch and PI3K blocked the down-regulation of IRS-1 and HSL induced by ADE-treated macrophages. Conclusion: Together, these data indicate that ADEs carrying Shh induce the M1 polarization of macrophages, which contributes to insulin resistance in adipocytes through the Ptch/PI3K pathway.

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Section: Introductionmentioning

confidence: 99%

Adipocyte-Derived Exosomes Carrying Sonic Hedgehog Mediate M1 Macrophage Polarization-Induced Insulin Resistance via Ptch and PI3K Pathways

Song

Han

Chen

et al. 2018

Cell Physiol Biochem

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“…[22] In another study, PSO consumption resulted in reduction of plasma TNF-α levels in mice. However, PSO treatment in dyslipidemic patients had no effect on the serum TNF-α in one study.…”

Section: Discussionmentioning

confidence: 99%

Effects of pomegranate seed oil on metabolic state of patients with Type 2 diabetes mellitus

et al. 2016

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Background:Rapid increasing prevalence of diabetes mellitus is a serious health concern in the world. New data determined that the pathogenesis of diabetes mellitus is chronic low-grade inflammation, resulting insulin resistance. Pomegranate seed oil (PSO) has anti-inflammatory effects; though it may reduce insulin resistance and improve glycemia in diabetes mellitus. The present study has been designed to investigate the effects of PSO as a natural dietary component on metabolic state of patients with Type 2 diabetes mellitus.Methods:In a randomized double-blind clinical trial study, 80 patients (28 men) with Type 2 diabetes were randomly allocated to the intervention and control groups. The intervention group consumed PSO capsules, containing 1000 mg PSO twice daily (2000 mg PSO), whereas controls take placebo for 8 weeks. The participants followed their previous dietary patterns and medication use. Dietary factors and metabolic factors including lipid profile, fasting plasma sugar, and insulin and were assayed at the baseline and after 8 weeks.Results:Participants in two intervention and control group were similar regarding anthropometric and the dietary factors at baseline and after trial (P > 0.05). Mean level of total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-density lipoprotein was not different significantly between groups after trial (P > 0.05). Consumption of PSO did not significantly affect the levels of parameters such as fasting blood sugar (FBS), insulin, HbA1c, alanine transferase, and homeostasis model assessment-insulin resistance.Conclusions:Consumption of 2000mg PSO per day for 8 weeks had no effect on FBS, insulin resistance and lipid profile in diabetic patients.

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“…In addition, treatment with PA was found to ameliorate TNF-α-induced alterations in proteins associated with mitochondrial dynamics like mitochondrial fission 1 protein and optic atrophy type 1. These findings suggest that PA can be considered as an active lead for the management of insulin resistance and associated mitochondrial dysfunctions [46] . Furthermore, PA was shown to inhibit the expression of TNF-α and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and upregulate PPAR-α-and γ-responsive genes in the tissues controlling glucose homeostasis in mice.…”

Section: Pa and Diabetes Mellitusmentioning

confidence: 92%

Hatice Asli Bedel, Nur Tukel Turgut, Aysegul Ugur Kurtoglu, Coskun Usta

Bedel¹,

Turgut²,

Kurtoğlu³

et al. 2017

pharmaceutical-sciences

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Bedel, et al.: Pharmacology of Punicic AcidPlant extracts and nutraceuticals are the most ancient and widespread form of medication employed by the general population. The pomegranate is a prehistoric, mystical and a highly differentiated fruit. Moreover, pomegranate is found in some medicinal systems as a cure for a variety of illnesses. Pomegranate has been used for a long time for nutraceutical purposes. Current research indicates that the most medicinally useful pomegranate components include ellagitannins, anthocyanins, anthocyanidins, flavonoids, estrogenic flavonols and flavones. Also pomegranate seed oil contains 64-83% punicic acid. Therefore, this review focussed on the effects of punicic acid, particularly those that have been reported such as the anticarcinogenic, antioxidant, antiinflammatory and antidiabetic effects. As nutraceuticals appear to play a major role in the prophylaxis of various diseases, punicic acid could be an important and phytoconstituent among these agents. Nutraceuticals are generally regarded as safe to use with lower incidence of side effects. In spite of all these reports it is obvious that there is a clear need for more clinical studies.

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Insulin resistance by TNF-α is associated with mitochondrial dysfunction in 3T3-L1 adipocytes and is ameliorated by punicic acid, a PPARγ agonist

Cited by 58 publications

References 50 publications

Adipocyte-Derived Exosomes Carrying Sonic Hedgehog Mediate M1 Macrophage Polarization-Induced Insulin Resistance via Ptch and PI3K Pathways

Adipocyte-Derived Exosomes Carrying Sonic Hedgehog Mediate M1 Macrophage Polarization-Induced Insulin Resistance via Ptch and PI3K Pathways

Effects of pomegranate seed oil on metabolic state of patients with Type 2 diabetes mellitus

Hatice Asli Bedel, Nur Tukel Turgut, Aysegul Ugur Kurtoglu, Coskun Usta

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