ArticleJournal of cachexia, sarcopenia and muscle2023
EXT418, a novel long-acting ghrelin, mitigates Lewis lung carcinoma induced cachexia in mice.
Article in Journal of cachexia, sarcopenia and muscle, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 12 citations in OpenAlex.
- Novel Long-Acting Ghrelin Analogue PEP-064 Restores Energy Balance in C26 and Lewis Lung Carcinoma-Induced cachexia in Mice.Journal of cachexia, sarcopenia and muscle · 2026Article
- Embryonic sheep placenta alleviates muscle-fat wasting symptoms and improves gut microbiome dysbiosis in cachexia mice.Biochemistry and biophysics reports · 2026Article
- Ghrelin Receptor Deletion or Pharmacological Inhibition Improves Muscle Function in Aging Male Mice.Aging cell · 2026Article
- Chitosan-Coated Liposomes for Intranasal Delivery of Ghrelin: Enhancing Bioavailability to the Central Nervous System.Pharmaceutics · 2025Article
- Vitamin D modulates gene expression in four major muscle tissues in Atlantic salmon.Scientific reports · 2025Article
- Exploring heterogeneity: a dive into preclinical models of cancer cachexia.American journal of physiology. Cell physiology · 2024Review
- Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies.Current issues in molecular biology · 2024Review
- Review
- EXT418, a novel long-acting ghrelin, mitigates Lewis lung carcinoma induced cachexia in mice.Journal of cachexia, sarcopenia and muscle · 2023Article
- Article
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGhrelin is a potential therapy for cachexia due to its orexigenic properties and anabolic effects on muscle and fat. However, its clinical use is limited by the short half-life of active (acylated) ghrelin (~11 min in humans). EXT418 is a novel long-acting, constitutively active ghrelin analog created by covalently linking it to a vitamin D derivative. Here, we evaluated the effects and mechanisms of action of EXT418 on Lewis lung carcinoma (LLC)-induced cachexia in mice.
methodsMale C57BL/6J mice (5- to 7-month-old) were implanted with 1 × 10
resultsIn tumour-bearing mice, administration of EXT418 daily or EOD partially prevented weight loss (T + V vs. T + 418 Daily, P = 0.030; and vs. T + 418 EOD, P = 0.020). Similar effects were observed in whole body fat and lean body mass. Grip strength in tumour-bearing mice was improved by EXT418 daily (P = 0.010) or EOD (P = 0.008) administration compared with vehicle-treated mice. These effects of EXT418 on weight and grip strength were partially independent of food intake. EXT418 daily administration also improved type IIA (P = 0.015), IIB (P = 0.037) and IIX (P = 0.050) fibre cross-sectional area (CSA) in tibialis anterior (TA) and EXT418 EOD improved CSA of IIB fibres in red gastrocnemius (GAS; P = 0.005). In skeletal muscles, tumour-induced increases in atrogenes Fbxo32 and Trim63 were ameliorated by EXT418 treatments (TA and GAS/plantaris, PL), which were independent of food intake. EXT418 administration decreased expression of the mitophagy marker Bnip3 (GAS/PL; P ≤ 0.010). Similar effects of EXT418 EOD were observed in p62 (GAS/PL; P = 0.039). In addition, EXT418 treatments ameliorated the tumour-induced elevation in muscle Il6 transcript levels (TA and GAS/PL), independently of food intake. Il-6 transcript levels in adipose tissue and circulating IL-10 were elevated in response to the tumour but these increases were not significant with EXT418 administration. Tumour mass was not altered by EXT418.
conclusionsEXT418 mitigates LLC-induced cachexia by attenuating skeletal muscle inflammation, proteolysis, and mitophagy, without affecting tumour mass and partially independent of food intake.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.