GLUCAGON-LIKE PEPTIDE 1 ANALOG LIRAGLUTIDE REDUCES TNF-&amp;alpha;-INDUCED OXIDATIVE STRESS AND INFLAMMATION

Shiraki, Aya; Oyama, Jun‐ichi; Komoda, Hiroshi; Node, Koichi

doi:10.1016/s0735-1097(12)60905-x

Cited by 25 publications

(37 citation statements)

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“…This suggests that the normalisation of abnormally activated inflammatory signalling by GLP-1 contributes to the decreased production of inflammatory cytokines and chemokines. Consistent with our results, it was recently reported that exendin-4 treatment showed anti-inflammatory effects on glomerular endothelial cells and macrophages [43], and that liraglutide, a longacting GLP-1 analogue, also inhibited NF-κB activation in human umbilical vein endothelial cells [44]. Energy intake in excess of energy expenditure may cause obesity and insulin resistance, while dysregulation of energy E x -4 U n t r e a t e d E x -4 U n t r e a t e d E x -4 U n t r e a t e d E x -4 U n t r e a t e d E x -4 U n t r e a t e d E x -4 Nuclei were stained with 4′-6-diamidino-2-phenylindole.…”

Section: Discussionsupporting

confidence: 93%

Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes

et al. 2012

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Aims/hypothesis Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM). Methods We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an ob/ob mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signalregulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro. Results Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated ob/ob mice. Macrophage populations (F4/80 + and F4/80 + CD11b + CD11c + cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated ob/ob mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated ob/ob mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated ob/ob mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM. Conclusions/interpretation We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity.

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Section: Discussionsupporting

confidence: 93%

Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes

et al. 2012

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“…8) Liraglutide, a glucagon-like peptide-1 analogue, has been found to inhibit oxidative stress and inflammatory response in the endothelial cells, heart and brain. 19,20,22,23) Results obtained from the present study contribute to further understanding of the mechanisms whereby liraglutide exerts a protective effect against high fat and high cholesterol diet induced hepatic steatosis, insulin resistance and liver dysfunction. Administration of liraglutide effectively alleviated hepatic oxidative stress and inflammatory response.…”

Section: Discussionmentioning

confidence: 60%

“…[16][17][18] It has been reported that liraglutide reduces tumor necrosis factor (TNF)-α or high glucose induced oxidative stress and inflammatory response in human endothelial cells. 19,20) Inhibition of protein kinase C (PKC) translocation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and nuclear factor (NF)-κB activation may contribute to the anti-oxidative and anti-inflammatory effects of liraglutide. 19,20) Recently, liraglutide has been reported to reduce the level of plasma reactive oxygen metabolites, an indicator of oxidative stress, in patients with type 2 diabetes.…”

mentioning

confidence: 99%

“…19,20) Inhibition of protein kinase C (PKC) translocation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and nuclear factor (NF)-κB activation may contribute to the anti-oxidative and anti-inflammatory effects of liraglutide. 19,20) Recently, liraglutide has been reported to reduce the level of plasma reactive oxygen metabolites, an indicator of oxidative stress, in patients with type 2 diabetes. 21) In addition, the anti-inflammatory effect of liraglutide has been demonstrated in the heart of mice with diabetes and the brain of mice with Alzheimer's disease.…”

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confidence: 99%

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The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease

Gao

Zeng

Zhang

et al. 2015

Biological & Pharmaceutical Bulletin

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Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been demonstrated to reduce hepatic steatosis. However, the mechanism of the lipid-lowering effect of liraglutide in the liver remains unclear. The aim of the present study was to investigate the beneficial effect of liraglutide on diet-induced non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism in rats. NAFLD was induced in Sprague-Dawley rats by feeding a high fat and high cholesterol (HFHC) diet. Liraglutide (0.6 mg/kg body weight/d) was injected intraperitoneally to the rats subjected to HFHC diet four weeks before sacrificing the animals. Body and liver weight, fasting blood glucose (FBG), fasting insulin, serum aminotransferase (ALT) and lipid accumulation in the liver were determined. Markers of oxidative stress, such as malondialdehyde (MDA), free fatty acid (FFAs), superoxide dismutase (SOD), and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) were detected by colorimetric detection or enzyme-linked immunosorbent assay (ELISA). Serum and hepatic adiponectin were measured by ELISA. The expression of c-Jun N-terminal kinase-1 (JNK-1) and phosphorylated JNK-1 were examined by Western blotting. Liraglutide improved insulin resistance, decreased hepatic steatosis and reversed liver dysfunction. The hepatic levels of MDA, FFAs, and TNF-α were significantly decreased versus controls. Meanwhile, administration of liraglutide significantly increased SOD and adiponectin levels in the liver and inhibited the expression of JNK-1 and phosphorylated JNK-1 versus control rats. Liraglutide exerted anti-oxidative and anti-inflammatory effects in the liver and consequently reversed hepatic steatosis and insulin resistance. Such effects might be mediated by the elevation of adiponectin levels and the inactivation of JNK-1.

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“…Most of the clinical trials, in line with animal studies, have reported a reduction of blood pressure after chronic treatment of GLP-1R agonists [148][149][150][151]. This may be explained, at least in part, by the ability of GLP-1 analogs to upregulate anti-oxidative enzymes and inhibit NFkB-mediated inflammatory signaling on endothelial cells [152,153], and to reduce oxidative stress by suppressing MAPK signaling pathways in peripheral lymphocytes of type 2 diabetic patients [154]. GLP-1-associated improvement of several cardiovascular markers suggests that therapies with GLP-1R agonists may have a positive effect on cardiovascular risk factors in patients with diabetes.…”

Section: How Conventional Diabetic Treatments May Ameliorate Endothelmentioning

confidence: 88%

Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options

Potenza

Nacci

Salvia

et al. 2017

Pharmacological Research

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Abstract:The association of obesity and diabetes, termed "diabesity", defines a combination of primarily metabolic disorders with insulin resistance as the underlying common pathophysiology. Cardiovascular disorders associated with diabesity represent the leading cause of morbidity and mortality in the Western world. This makes diabesity, with its rising impacts on both health and economics, one of the most challenging biomedical and social threats of present century. The emerging comprehension of the genes whose alteration confers inter-individual differences on risk factors for diabetes or obesity, together with the potential role of genetically determined variants on mechanisms controlling responsiveness, effectiveness and safety of anti-diabetic therapy underlines the need of additional knowledge on molecular mechanisms involved in the pathophysiology of diabesity. Endothelial cell dysfunction, resulting from the unbalanced production of endothelialderived vascular mediators, is known to be present at the earliest stages of insulin resistance and obesity, and may precede the clinical diagnosis of diabetes by several years. Once considered as a mere consequence of metabolic abnormalities, it is now clear that endothelial dysfunctional activity may play a pivotal role in the progression of diabesity. In the vicious circle where vascular defects and metabolic disturbances worsen and reinforce each other, a low-grade, chronic, and 'cold' inflammation (metaflammation) has been suggested to serve as the pathophysiological link that binds endothelial and metabolic dysfunctions. In this paradigm, it is important to consider how traditional antidiabetic treatments (specifically addressing metabolic dysregulation) may directly impact on inflammatory processes or cardiovascular function. Indeed, not all drugs currently available to treat diabetes possess the same anti-inflammatory potential, or target endothelial cell function equally. Perspective strategies pointing at reducing metaflammation or directly addressing endothelial dysfunction may disclose beneficial consequences on metabolic regulation. This review focuses on existing and potential new approaches ameliorating endothelial dysfunction and vascular inflammation in the context of diabesity.

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GLUCAGON-LIKE PEPTIDE 1 ANALOG LIRAGLUTIDE REDUCES TNF-α-INDUCED OXIDATIVE STRESS AND INFLAMMATION

Cited by 25 publications

References 0 publications

Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes

Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes

The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease

Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options

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