Agomelatine protects against obesity-induced renal injury by inhibiting endoplasmic reticulum stress/apoptosis pathway in rats

Cherngwelling, Rada; Pengrattanachot, Nattavadee; Swe, Myat Theingi; Thongnak, Laongdao; Promsan, Sasivimon; Phengpol, Nichakorn; Sutthasupha, Prempree; Lungkaphin, Anusorn

doi:10.1016/j.taap.2021.115601

Cited by 11 publications

(7 citation statements)

References 56 publications

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“…Our results show that agomelatine treatment lowered body weight gain and fat accumulation in a similar manner to previously observed for melatonin [37] and metformin [38], as well as improved obesity-associated glucose intolerance. This confirms previous experimental observations that associate weight decrease and enhanced insulin sensitivity with the regulation of metabolic clock and/or the increase of the energy expenditure/intake ratio [39][40][41]. Although some preclinical studies have indicated that melatonin lowers body weight and visceral fat accumulation [37,39], this has not been confirmed in humans [42].…”

Section: Discussionsupporting

confidence: 80%

The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome.

Diez-Echave,

Vezza,

Algieri

et al. 2024

Preprint

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Background and Purpose: Melatonin has shown beneficial effects on obesity, both in humans and experimental models, via regulating the altered circadian rhythm and thus ameliorating the gut dysbiosis associated with this metabolic condition. However, its clinical use is limited, mostly due to its short half-life. Agomelatine is an agonist of the melatonin receptors that could be used to manage obesity and offer a better profile than melatonin. Experimental Approach: Male C57BL/6 mice were fed a high fat diet and orally treated for five weeks with agomelatine, or melatonin or metformin, used as control drugs. Metabolic profile, inflammatory status, vascular dysfunction and intestinal microbiota composition were assessed. Key Results: Agomelatine lessened body weight gain, enhanced glucose and lipid metabolisms, and improved insulin resistance. It also reduced the obesity-associated inflammatory status and endothelial dysfunction, probably linked to its effect on gut dysbiosis, consisting of the restoration of bacterial populations with key functions, such as short chain fatty acid production. Conclusions and Implications: Agomelatine can be considered as a novel therapeutic tool for the management of human obesity and its associated comorbidities.

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Section: Discussionsupporting

confidence: 80%

The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome.

Diez-Echave,

Vezza,

Algieri

et al. 2024

Preprint

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“…Notably, in the CTD, bromoethylamine is reported to interact with hepatitis A virus cellular receptor 1 and natriuretic peptide receptor 1, which coincide with the genes predicted in this study. Additionally, both genes are associated with fibrosis ( Cherngwelling et al, 2021 ; Priego et al, 2021 ), which is an important phenotype that occurs throughout the progression of LUAD ( Angel et al, 2020 ). Moreover, these two genes also show strong associations with kidney-related diseases ( Kanki et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Lung adenocarcinoma-related target gene prediction and drug repositioning

Huang

Siriwanna²,

Cho³

et al. 2022

Front. Pharmacol.

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Lung cancer is the leading cause of cancer deaths globally, and lung adenocarcinoma (LUAD) is the most common type of lung cancer. Gene dysregulation plays an essential role in the development of LUAD. Drug repositioning based on associations between drug target genes and LUAD target genes are useful to discover potential new drugs for the treatment of LUAD, while also reducing the monetary and time costs of new drug discovery and development. Here, we developed a pipeline based on machine learning to predict potential LUAD-related target genes through established graph attention networks (GATs). We then predicted potential drugs for the treatment of LUAD through gene coincidence-based and gene network distance-based methods. Using data from 535 LUAD tissue samples and 59 precancerous tissue samples from The Cancer Genome Atlas, 48,597 genes were identified and used for the prediction model building of the GAT. The GAT model achieved good predictive performance, with an area under the receiver operating characteristic curve of 0.90. 1,597 potential LUAD-related genes were identified from the GAT model. These LUAD-related genes were then used for drug repositioning. The gene overlap and network distance with the target genes were calculated for 3,070 drugs and 672 preclinical compounds approved by the US Food and Drug Administration. At which, bromoethylamine was predicted as a novel potential preclinical compound for the treatment of LUAD, and cimetidine and benzbromarone were predicted as potential therapeutic drugs for LUAD. The pipeline established in this study presents new approach for developing targeted therapies for LUAD.

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“…ER stress is activated in various tissues under conditions related to obesity, and hepatic ER stress contributes to the development of steatosis and insulin resistance [7]. Furthermore, abnormal lipid accumulation in obesity can also induce ER stress and cellular apoptosis in several tissue types [8]. ER stress is regarded as a central feature of insulin resistance at the molecular, cellular, and organismal levels [9].…”

Section: Introductionmentioning

confidence: 99%

Supplementation of quinoa regulates glycolipid metabolism and endoplasmic reticulum stress in the high-fat diet-induced female obese mice

Liu²,

Yang

et al. 2021

Nutr Metab (Lond)

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Objective To explore the effects of the quinoa diet on glycolipid metabolism and endoplasmic reticulum (ER) stress in an obese mouse model. Methods Six-week-old C57BL/6J female mice have received a high-fat diet (HFD) to induce obesity and subsequently were treated with a quinoa diet for 12 weeks. During this period, fasting blood glucose, body fat and insulin resistance were measured regularly. At the end of the experiment, mouse serum and liver tissue were collected. The differences in glucose and lipid metabolism were analyzed, and liver tissue pathological morphology, liver endoplasmic reticulum stress-related mRNA and protein levels, and serum oxidative stress levels were measured. Results Quinoa diet could significantly reduce the level of blood glucose, triglyceride, cholesterol, low-density lipoprotein, improve glucose tolerance, as well as improve histological changes of liver tissues in obese mice (P < 0.05 or < 0.01). Besides, quinoa could improve oxidative stress indicators such as GSH, and MDA (P < 0.05 or < 0.01). Furthermore, quinoa can down-regulate mRNA expression of ER stress markers eIF2α, GRP78, and CHOP in the liver of obese mice (P < 0.05 or < 0.01). Conclusions Quinoa supplementation can improve glycolipid metabolism, regulate ER stress, and alleviate obesity in HFD-induced mice.

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Agomelatine protects against obesity-induced renal injury by inhibiting endoplasmic reticulum stress/apoptosis pathway in rats

Cited by 11 publications

References 56 publications

The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome.

The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome.

Lung adenocarcinoma-related target gene prediction and drug repositioning

Supplementation of quinoa regulates glycolipid metabolism and endoplasmic reticulum stress in the high-fat diet-induced female obese mice

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