Background: In chronic heart failure (CHF), cachexia is a hallmark of the terminal stage of this disease and is associated with a severely reduced quality of life and poor prognosis. Therapeutic options are currently not available. Ghrelin and its analogues BIM-28125 and BIM-28131 (now known as RM-131) have been shown to increase weight in a rat model of CHF. It has been further demonstrated that the expression of myostatin, a negative regulator of skeletal muscle mass, is increased in CHF. The aim of the study was to investigate the influence of ghrelin or its analogues on myostatin in CHF.
Methods: In an animal model of CHF, Sprague-Dawley rats received either ghrelin or two ghrelin analogues BIM-28125 and BIM-28131 in two different concentrations (50 and 500 nmol/kg/day) compared to placebo. The compounds were delivered using osmotic mini pumps. The expression of myostatin was analyzed in skeletal muscle by RT-PCR and Western blot, and muscle mass of gastrocnemius muscle was measured. The plasma levels of tumor necrosis factor alpha (TNF-α) were measured.
Results: The relative weight of the gastrocnemius muscle of the sham-operated group was significantly increased compared to placebo-treated CHF rats. The application of ghrelin analogue BIM-28125 and BIM-28131 in their higher concentrations led to a significant reduction in myostatin mRNA expression in comparison to placebo. Myostatin protein expression was significantly reduced in both concentrations of ghrelin and BIM-28131 and in the lower concentration of BIM-28125. The increase of TNF-α plasma concentration in the CHF-animals could be abolished by all used substances.
Conclusions: In an animal model of CHF, the expression of myostatin is significantly reduced in the skeletal muscle after application of ghrelin and most concentrations of its analogues BIM-28125 and BIM-28131 possibly due to anti-inflammatory effects.
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http://dx.doi.org/10.1007/s13539-012-0085-3 | DOI Listing |
Pharmacol Res Perspect
February 2025
Department of Cardiology and Pneumology, University of Göttingen Medical Center, Göttingen, Germany.
Cachexia is a multifactorial metabolic syndrome characterized by weight and skeletal muscle loss caused by underlying illnesses such as cancer, heart failure, and renal failure. Inflammation, insulin resistance, increased muscle protein degradation, decreased food intake, and anorexia are the primary pathophysiological drivers of cachexia. Cachexia causes physical deterioration and functional impairment, loss of quality of life, lower response to active treatment, and ultimately morbidity and mortality, while the difficulties in tackling cachexia in its advanced phases and the heterogeneity of the syndrome among patients require an individualized and multidisciplinary approach from an early stage.
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February 2025
Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic. Electronic address:
Liver-enriched antimicrobial peptide 2 (LEAP2) is a natural antagonist/inverse agonist of ghrelin receptor GHSR. Its truncated palmitoylated analog palm-LEAP2(1-14) promised anti-obesity properties because it exhibited favourable stability and an acute anorexigenic effect in our previous studies. Here we demonstrate desirable palm-LEAP2(1-14) pharmacokinetics, with significant levels of the peptide persisting in mouse blood 3 h after its subcutaneous administration.
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December 2024
Human Translational Physiology, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
The endocrine consequences of weight loss by bariatric surgery (BS) and caloric restriction are not fully understood but contribute to variable improvements in insulin sensitivity and cardiometabolic health. This study compared changes in insulin sensitivity and plasma concentrations of gut peptides 8 weeks and 1 year after BS and a low-calorie diet (LCD). Nineteen female patients with obesity self-selected BS (gastric bypass [n = 5] or sleeve gastrectomy [n = 7]) or LCD (n = 7) in this parallel-arm, prospective observational study.
View Article and Find Full Text PDFNutrients
December 2024
Grupo de Neuropsicofarmacología, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Unidades Clínicas de Neurología y Salud Mental, 29010 Málaga, Spain.
Background/objectives: Alzheimer's disease (AD), a leading cause of dementia, lacks effective long-term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Aβ) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut.
View Article and Find Full Text PDFNutrients
November 2024
Department of Nano Bio Engineering, Seoul National University of Science and Technology, 232, Gongneung-ro, Nowon-gu, Seoul 01811, Republic of Korea.
Barley dietary fiber (BDF), particularly β-glucan, has shown potential in modulating postprandial glycemic responses and improving metabolic health. This study aimed to assess the effects of Saechalssalbori ( L.), a glutinous barley variety rich in β-glucan, on postprandial blood glucose, insulin, glucagon, triglycerides, and appetite-related hormones in healthy adults.
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