Metformin ameliorates olanzapine-induced insulin resistance via suppressing macrophage infiltration and inflammatory responses in rats

Guo, Chongfeng; Liu, Jinxin; Li, Huqun

doi:10.1016/j.biopha.2020.110912

Cited by 20 publications

(14 citation statements)

References 45 publications

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“…Therefore, AuNCs did not largely reduce weight gain in the early stage of administration. This is consistent with previous studies reporting that although subjects such as betahistine, metformin and NESS06SM significantly affect the hypothalamic H1Rs, AMPK and POMC, subjects required 5–14 days of treatment to begin to evidentially reduce olanzapine-induced weight gain 28 , 29 , 67 , 68 . Moreover, reductions in BAT temperature and reductions in BAT thermogenesis markers normally occurred in the late stages of olanzapine-induced obesity 30 .…”

Section: Discussionsupporting

confidence: 92%

Gold nanoclusters eliminate obesity induced by antipsychotics

Jing

Zhang

et al. 2022

Sci Rep

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Obesity induced by antipsychotics have plagued more than 20 million people worldwide. However, no drug is available to eliminate the obesity induced by antipsychotics. Here we examined the effect and potential mechanisms of a gold nanoclusters (AuNCs) modified by N-isobutyryl-L-cysteine on the obesity induced by olanzapine, the most prescribed but obesogenic antipsychotics, in a rat model. Our results showed that AuNCs completely prevented and reversed the obesity induced by olanzapine and improved glucose metabolism profile in rats. Further mechanism investigations revealed that AuNCs exert its anti-obesity function through inhibition of olanzapine-induced dysfunction of histamine H1 receptor and proopiomelanocortin signaling therefore reducing hyperphagia, and reversing olanzapine-induced inhibition of uncoupling-protein-1 signaling which increases thermogenesis. Together with AuNCs’ good biocompatibility, these findings not only provide AuNCs as a promising nanodrug candidate for treating obesity induced by antipsychotics, but also open an avenue for the potential application of AuNCs-based nanodrugs in treating general obesity.

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Section: Discussionsupporting

confidence: 92%

Gold nanoclusters eliminate obesity induced by antipsychotics

Jing

Zhang

et al. 2022

Sci Rep

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“…Interestingly, these antiinflammatory effects seemed to be mediated by inducible 6-phosphofructokinase-2 (iPFK2) as they were not seen in iPFK2-knockdown adipocytes and there was no increase in AMPK activation. Anti-inflammatory effects were also seen in a mouse model of olanzapine-induced insulin resistance in which metformin not only reduced common inflammatory cytokines such as TNF-α, IL-1β and IL-6 but also counteracted macrophage infiltration and M1 polarisation (Guo et al 2021a). Similar effects have been shown in obese high fat-fed mice with a clear shift in polarisation from M1 to M2 in those animals that received metformin (Jing et al 2018).…”

Section: Adipose Tissuementioning

confidence: 96%

Metformin as an anti-inflammatory agent: a short review

Kristófi

Eriksson

2021

Journal of Endocrinology

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Metformin is a biguanide drug widely used as the initial treatment of type 2 diabetes. Despite its widespread use, its precise mechanisms of action remain incompletely characterised. Its effect in lowering blood glucose is largely related to suppression of gluconeogenesis in the liver, which is probably accomplished by partial inhibition of the mitochondrial respiratory chain complex 1 with a subsequent increase in intracellular AMP levels and activation of AMP kinase. Several local and systemic anti-inflammatory effects of metformin have been described. Many of these effects seem to be mediated by AMP kinase activation and downstream effects inhibiting mTOR and NF-κB pro-inflammatory signalling cascades. However, there are also studies describing actions independent of AMP kinase action. In this review, we summarise the currently known mechanisms of metformin on inflammatory pathways and the clinical evidence underpinning the use of metformin as a potential anti-inflammatory drug.

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“…Meanwhile, DS and DG would display a beneficial effect in liver, through the decrease of OLZ-induced lipid accumulation. These differential effects in skeletal muscle and liver cells also suggest that there are direct effects of OLZ over each cell type that could be acting together with the inflammatory hypothesis [48,49].…”

Section: Discussionmentioning

confidence: 96%

Anthocyanins from Aristotelia chilensis Prevent Olanzapine-Induced Hepatic-Lipid Accumulation but Not Insulin Resistance in Skeletal Muscle Cells

et al. 2021

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Type 2 diabetes and obesity are major problems worldwide and dietary polyphenols have shown efficacy to ameliorate signs of these diseases. Anthocyanins from berries display potent antioxidants and protect against weight gain and insulin resistance in different models of diet-induced metabolic syndrome. Olanzapine is known to induce an accelerated form of metabolic syndrome. Due to the aforementioned, we evaluated whether delphinidin-3,5-O-diglucoside (DG) and delphinidin-3-O-sambubioside-5-O-glucoside (DS), two potent antidiabetic anthocyanins isolated from Aristotelia chilensis fruit, could prevent olanzapine-induced steatosis and insulin resistance in liver and skeletal muscle cells, respectively. HepG2 liver cells and L6 skeletal muscle cells were co-incubated with DG 50 μg/mL or DS 50 μg/mL plus olanzapine 50 μg/mL. Lipid accumulation was determined in HepG2 cells while the expression of p-Akt as a key regulator of the insulin-activated signaling pathways, mitochondrial function, and glucose uptake was assessed in L6 cells. DS and DG prevented olanzapine-induced lipid accumulation in liver cells. However, insulin signaling impairment induced by olanzapine in L6 cells was not rescued by DS and DG. Thus, anthocyanins modulate lipid metabolism, which is a relevant factor in hepatic tissue, but do not significantly influence skeletal muscle, where a potent antioxidant effect of olanzapine was found.

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Metformin ameliorates olanzapine-induced insulin resistance via suppressing macrophage infiltration and inflammatory responses in rats

Cited by 20 publications

References 45 publications

Gold nanoclusters eliminate obesity induced by antipsychotics

Gold nanoclusters eliminate obesity induced by antipsychotics

Metformin as an anti-inflammatory agent: a short review

Anthocyanins from Aristotelia chilensis Prevent Olanzapine-Induced Hepatic-Lipid Accumulation but Not Insulin Resistance in Skeletal Muscle Cells

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