Win 55,212-2, atenolol and subdiaphragmatic vagotomy prevent acceleration of gastric emptying induced by cachexia via Yoshida-AH-130 cells in rats

Cavalcante, Mickael Laudrup de Sousa; Silva, Mariana Sousa; Cavalcante, Ana Karolina Martins; Santos, Raisa de Oliveira; Nunes, Dyerson Danrlei Tavares; Busquets, Sílvia; Argilés, Josep Μ.; Seelaender, Marília; Neto, Emídio Marques de Matos; Santos, Armênio Aguiar dos; Silva, Moisés Tolentino Bento da

doi:10.1016/j.ejphar.2020.173087

Cited by 6 publications

(5 citation statements)

References 72 publications

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“…Finally, we also found an increased average faeces weight that could not be explained by a water content variation but rather by an increased faecal protein concentration ( Figure 7D–7F). A recent study performed in cachectic rats showed that cachexia accelerated gastric emptying 89 . This study corroborates our finding that gut motility is affected in C26 mice and likely impacts protein and amino acid catabolism in the gastrointestinal tract.…”

Section: Resultssupporting

confidence: 92%

“…A recent study performed in cachectic rats showed that cachexia accelerated gastric emptying. 89 This study corroborates our finding that gut motility is affected in C26 mice and likely impacts protein and amino acid catabolism in the gastrointestinal tract. Faecal protein content is not commonly reported in cancer cachexia.…”

Section: Several Gut Microbial Activities Are Decreased In Cancer Cac...supporting

confidence: 91%

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Multi‐compartment metabolomics and metagenomics reveal major hepatic and intestinal disturbances in cancer cachectic mice

Pötgens

Thibaut

Joudiou

et al. 2021

J cachexia sarcopenia muscle

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Background Cancer cachexia is a multifactorial syndrome characterized by multiple metabolic dysfunctions. Besides the muscle, other organs such as the liver and the gut microbiota may also contribute to this syndrome. Indeed, the gut microbiota, an important regulator of the host metabolism, is altered in the C26 preclinical model of cancer cachexia. Interventions targeting the gut microbiota have shown benefits, but mechanisms underlying the host-microbiota crosstalk in this context are still poorly understood. Methods To explore this crosstalk, we combined proton nuclear magnetic resonance ( 1 H-NMR) metabolomics in multiple compartments with 16S rDNA sequencing. These analyses were complemented by molecular and biochemical analyses, as well as hepatic transcriptomics.Results 1 H-NMR revealed major changes between control (CT) and cachectic (C26) mice in the four analysed compartments (i.e. caecal content, portal vein, liver, and vena cava). More specifically, glucose metabolism pathways in the C26 model were altered with a reduction in glycolysis and gluconeogenesis and an activation of the hexosamine pathway, arguing against the existence of a Cori cycle in this model. In parallel, amino acid uptake by the liver, with an up to four-fold accumulation of nine amino acids (q-value <0.05), was mainly used for acute phase response proteins synthesis rather than to fuel the tricarboxylic acid cycle and gluconeogenesis. We also identified a 35% reduction in hepatic carnitine levels (q-value <0.05) and a lower activation of the phosphatidylcholine pathway as potential contributors to the hepatic steatosis present in this model. Our work also reveals a reduction of different beneficial intestinal bacterial activities in cancer cachexia. We found decreased levels of two short-chain fatty acids, acetate and butyrate (72% and 88% reduction in C26 caecal content; q-value <0.001), and a reduction in aromatic amino acid metabolites, which may contribute to the altered intestinal homeostasis in these mice. A member of the Ruminococcaceae family (ASV 2) was identified as the main bacterium responsible for the drop in butyrate. Finally, we report a two-fold intestinal transit acceleration (P-value <0.001) as a key factor shaping the gut microbiota composition and activity in cancer cachexia, which together lead to a faecal loss of proteins and amino acids. Conclusions Our work highlights new metabolic pathways potentially involved in cancer cachexia and further supports the interest of exploring the gut microbiota composition and activity, as well as intestinal transit, in cancer patients with and without cachexia.

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Section: Resultssupporting

confidence: 92%

Section: Several Gut Microbial Activities Are Decreased In Cancer Cac...supporting

confidence: 91%

Multi‐compartment metabolomics and metagenomics reveal major hepatic and intestinal disturbances in cancer cachectic mice

Pötgens

Thibaut

Joudiou

et al. 2021

J cachexia sarcopenia muscle

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“…WIN administered prior to cachexia induction caused no difference in food intake or body weight but caused a significant reduction in cachexia index from 38.5 ± 2.1% to 25.8 ± 2.7%. Validating previous results, WIN administered rats not exposed to cachexia displayed significant decreases in body weight (p < 0.05) [82].…”

Section: Win 55212-2supporting

confidence: 84%

Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs

Murphy

Foll

2020

Biomolecules

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Obesity rates are increasing worldwide and there is a need for novel therapeutic treatment options. The endocannabinoid system has been linked to homeostatic processes, including metabolism, food intake, and the regulation of body weight. Rimonabant, an inverse agonist for the cannabinoid CB1 receptor, was effective at producing weight loss in obese subjects. However, due to adverse psychiatric side effects, rimonabant was removed from the market. More recently, we reported an inverse relationship between cannabis use and BMI, which has now been duplicated by several groups. As those results may appear contradictory, we review here preclinical and clinical studies that have studied the impact on body weight of various cannabinoid CB1 drugs. Notably, we will review the impact of CB1 inverse agonists, agonists, partial agonists, and neutral antagonists. Those findings clearly point out the cannabinoid CB1 as a potential effective target for the treatment of obesity. Recent preclinical studies suggest that ligands targeting the CB1 may retain the therapeutic potential of rimonabant without the negative side effect profile. Such approaches should be tested in clinical trials for validation.

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“…Of note, preclinical data vary greatly in terms of anorexic/anti-anorexic effects of cannabinoids, most likely because the effect of cannabinoids on food intake is highly dependent on both dose and type of cannabinoid used. For example, 100 μg/kg of CP 55,940 (a synthetic cannabinoid) had significant anorexic effects and caused a decrease in body weight in rats ( McGregor et al, 1996 ), whereas WIN 55212-2 (2 mg/kg) prevented the acceleration of gastric emptying induced by cachexia in rats ( de Sousa Cavalcante et al, 2020 ). However, some of the candidates with positive results in the preclinical studies have translated towards clinical trials in both cancer and non-cancer patients.…”

Section: Palliation Of Cancer-associated Symptomsmentioning

confidence: 99%

Should oncologists trust cannabinoids?

et al. 2023

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Cannabis enjoyed a “golden age” as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians are still not convinced by the existing evidence-based data to guide their treatment plans. Physicians should prescribe cannabis only if a careful explanation can be provided and follow up response evaluation ensured, making it mandatory for them to be up to date with the positive and also negative aspects of the cannabis in the case of cancer patients. Consequently, this article aims to bring some clarifications to clinicians regarding the sometimes-confusing various nomenclature under which this plant is mentioned, current legislation and the existing evidence (both preclinical and clinical) for the utility of cannabinoids in cancer patients, for either palliation of the associated symptoms or even the potential antitumor effects that cannabinoids may have.

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Win 55,212-2, atenolol and subdiaphragmatic vagotomy prevent acceleration of gastric emptying induced by cachexia via Yoshida-AH-130 cells in rats

Cited by 6 publications

References 72 publications

Multi‐compartment metabolomics and metagenomics reveal major hepatic and intestinal disturbances in cancer cachectic mice

Multi‐compartment metabolomics and metagenomics reveal major hepatic and intestinal disturbances in cancer cachectic mice

Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs

Should oncologists trust cannabinoids?

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