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Physiological Reports Oct 2023We evaluated whether anserine, a methylated analog of the dipeptide carnosine, is present in the cardiac and skeletal muscles of humans and whether the CARNMT1 gene,...
We evaluated whether anserine, a methylated analog of the dipeptide carnosine, is present in the cardiac and skeletal muscles of humans and whether the CARNMT1 gene, which encodes the anserine synthesizing enzyme carnosine-N-methyltransferase, is expressed in human skeletal muscle. We found that anserine is present at low concentrations (low micromolar range) in both cardiac and skeletal muscles, and that anserine content in skeletal muscle is ~15 times higher than in cardiac muscle (cardiac muscle: 10.1 ± 13.4 μmol·kg of dry muscle, n = 12; skeletal muscle: 158.1 ± 68.5 μmol·kg of dry muscle, n = 11, p < 0.0001). Anserine content in the heart was highly variable between individuals, ranging from 1.4 to 45.4 μmol·kg of dry muscle, but anserine content was not associated with sex, age, or body mass. We also showed that CARNMT1 gene is poorly expressed in skeletal muscle (n = 10). This is the first study to demonstrate that anserine is present in the ventricle of the human heart. The presence of anserine in human heart and the confirmation of its expression in human skeletal muscle open new avenues of investigation on the specific and differential physiological functions of histidine dipeptides in striated muscles.
Topics: Humans; Anserine; Carnosine; Muscle, Skeletal; Dipeptides; Myocardium
PubMed: 37771070
DOI: 10.14814/phy2.15833 -
Antioxidants (Basel, Switzerland) Jun 2023Carnosine and anserine supplementation markedLy reduce diabetic nephropathy in rodents. The mode of nephroprotective action of both dipeptides in diabetes, via local...
Carnosine and anserine supplementation markedLy reduce diabetic nephropathy in rodents. The mode of nephroprotective action of both dipeptides in diabetes, via local protection or improved systemic glucose homeostasis, is uncertain. Global carnosinase-1 knockout mice (-KO) and wild-type littermates (WT) on a normal diet (ND) and high fat diet (HFD) ( = 10/group), with streptozocin (STZ)-induced type-1 diabetes ( = 21-23/group), were studied for 32 weeks. Independent of diet, -KO mice had 2- to 10-fold higher kidney anserine and carnosine concentrations than WT mice, but otherwise a similar kidney metabolome; heart, liver, muscle and serum anserine and carnosine concentrations were not different. Diabetic -KO mice did not differ from diabetic WT mice in energy intake, body weight gain, blood glucose, HbA1c, insulin and glucose tolerance with both diets, whereas the diabetes-related increase in kidney advanced glycation end-product and 4-hydroxynonenal concentrations was prevented in the KO mice. Tubular protein accumulation was lower in diabetic ND and HFD -KO mice, interstitial inflammation and fibrosis were lower in diabetic HFD -KO mice compared to diabetic WT mice. Fatalities occurred later in diabetic ND -KO mice versus WT littermates. Independent of systemic glucose homeostasis, increased kidney anserine and carnosine concentrations reduce local glycation and oxidative stress in type-1 diabetic mice, and mitigate interstitial nephropathy in type-1 diabetic mice on HFD.
PubMed: 37372000
DOI: 10.3390/antiox12061270 -
Nutrients Jul 2023Red meat and animal-sourced protein are often disparaged as risk factors for developing metabolic syndrome, while emerging research has shown the beneficial effects of... (Review)
Review
Red meat and animal-sourced protein are often disparaged as risk factors for developing metabolic syndrome, while emerging research has shown the beneficial effects of dietary taurine, creatine, carnosine, and anserine which are all exclusively abundant in red meat. Thus, it is imperative to highlight the available evidence to help promote red meat as part of a well-balanced diet to optimize human health. In this study, a bibliometric analysis was conducted to investigate the current research status of dietary taurine, creatine, carnosine, and anserine with metabolic syndrome, identify research hotspots, and delineate developmental trends by utilizing the visualization software CiteSpace. A total of 1094 publications were retrieved via the Web of Science Core Collection from 1992 to 2022. There exists a gradual increase in the number of publications on this topic, but there is still much room for research papers to rise. The United States has participated in the most studies, followed by China and Japan. The University of Sao Paulo was the research institute contributing the most; Kyung Ja Chang and Sanya Roysommuti have been identified as the most prolific authors. The analysis of keywords reveals that obesity, lipid profiles, blood pressure, and glucose metabolism, as well as ergogenic aid and growth promoter have been the research hotspots. Inflammation and diabetic nephropathy will likely be frontiers of future research related to dietary taurine, creatine, carnosine, and anserine. Overall, this paper may provide insights for researchers to further delve into this field and enlist the greater community to re-evaluate the health effects of red meat.
PubMed: 37571314
DOI: 10.3390/nu15153374 -
Journal of Cachexia, Sarcopenia and... Aug 2023Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin-linked proteolysis. These processes are sensitive to changes in...
BACKGROUND
Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin-linked proteolysis. These processes are sensitive to changes in intracellular pH ([pH] ) and reactive oxygen species, which in skeletal muscle are partly regulated by histidyl dipeptides, such as carnosine. These dipeptides, synthesized by the enzyme carnosine synthase (CARNS), remove lipid peroxidation-derived aldehydes, and buffer [pH] . Nevertheless, their role in muscle wasting has not been studied.
METHODS
Histidyl dipeptides in the rectus abdominis (RA) muscle and red blood cells (RBCs) of male and female controls (n = 37), weight stable (WS: n = 35), and weight losing (WL; n = 30) upper gastrointestinal cancer (UGIC) patients, were profiled by LC-MS/MS. Expression of enzymes and amino acid transporters, involved in carnosine homeostasis, was measured by Western blotting and RT-PCR. Skeletal muscle myotubes were treated with Lewis lung carcinoma conditioned medium (LLC CM), and β-alanine to study the effects of enhancing carnosine production on muscle wasting.
RESULTS
Carnosine was the predominant dipeptide present in the RA muscle. In controls, carnosine levels were higher in men (7.87 ± 1.98 nmol/mg tissue) compared with women (4.73 ± 1.26 nmol/mg tissue; P = 0.002). In men, carnosine was significantly reduced in both the WS (5.92 ± 2.04 nmol/mg tissue, P = 0.009) and WL (6.15 ± 1.90 nmol/mg tissue; P = 0.030) UGIC patients, compared with controls. In women, carnosine was decreased in the WL UGIC (3.42 ± 1.33 nmol/mg tissue; P = 0.050), compared with WS UGIC patients (4.58 ± 1.57 nmol/mg tissue), and controls (P = 0.025). Carnosine was significantly reduced in the combined WL UGIC patients (5.12 ± 2.15 nmol/mg tissue) compared with controls (6.21 ± 2.24 nmol/mg tissue; P = 0.045). Carnosine was also significantly reduced in the RBCs of WL UGIC patients (0.32 ± 0.24 pmol/mg protein), compared with controls (0.49 ± 0.31 pmol/mg protein, P = 0.037) and WS UGIC patients (0.51 ± 0.40 pmol/mg protein, P = 0.042). Depletion of carnosine diminished the aldehyde-removing ability in the muscle of WL UGIC patients. Carnosine levels were positively associated with decreases in skeletal muscle index in the WL UGIC patients. CARNS expression was decreased in the muscle of WL UGIC patients and myotubes treated with LLC-CM. Treatment with β-alanine, a carnosine precursor, enhanced endogenous carnosine production and decreased ubiquitin-linked protein degradation in LLC-CM treated myotubes.
CONCLUSIONS
Depletion of carnosine could contribute to muscle wasting in cancer patients by lowering the aldehyde quenching abilities. Synthesis of carnosine by CARNS in myotubes is particularly affected by tumour derived factors and could contribute to carnosine depletion in WL UGIC patients. Increasing carnosine in skeletal muscle may be an effective therapeutic intervention to prevent muscle wasting in cancer patients.
Topics: Female; Humans; Male; Aldehydes; beta-Alanine; Carcinoma, Lewis Lung; Carnosine; Chromatography, Liquid; Dipeptides; Muscle, Skeletal; Muscular Atrophy; Tandem Mass Spectrometry; Ubiquitins
PubMed: 37199284
DOI: 10.1002/jcsm.13258 -
Marine Drugs Aug 2023Anserine is a naturally occurring histidine dipeptide with significant antioxidant activities. This study aimed to investigate the preventive mechanism of anserine on...
Anserine is a naturally occurring histidine dipeptide with significant antioxidant activities. This study aimed to investigate the preventive mechanism of anserine on tert-butyl hydroperoxide (TBHP)-induced liver damage in a normal human liver cell line (L-02 cells). The L-02 cells were pretreated with anserine (10, 20, and 40 mmol/L) and then induced with 400 μmol/L of TBHP for 4 h. The results showed that the survival rates of L-02 cells and the contents of GSH were significantly increased with the pretreatment of anserine; the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the extracellular fluid were sharply decreased; and the formation of reactive oxygen species (ROS), nuclear fragmentation, and apoptosis were significantly inhibited. In addition, anserine could bind to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) with a binding force of -7.2 kcal/mol; the protein expressions of nuclear factor-erythroid 2-related factor-2 (Nrf2), quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and Bcl-2 were upregulated by anserine in TBHP-induced L-02 cells, with the downregulation of p-JNK and caspase-3. In conclusion, anserine might alleviated liver injury in L-02 cells via regulating related proteins in the Keap1-Nrf2 and JNK-Caspase-3 signaling pathways.
PubMed: 37755089
DOI: 10.3390/md21090477