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SARMs jako modulatory funkcji metabolicznych i stresu oksydacyjnego tkanki tłuszczowej i serca w szczurzym modelu otyłości – badania in vitro i in vivo
The effects of time-restricted eating and Ramadan fasting on gut microbiota composition: a systematic review of human and animal studies
Abstract Context It is well known that the microbiome undergoes cyclical diurnal rhythms. It has thus been hypothesized that meal timing may affect gut microbial composition, function, and host health. Objective This review aims to examine the effects of time-restricted eating (TRE) and Ramadan fasting (RF) on the composition of the gut microbiota in animal and human studies. The associations between composition of microbiota and host metabolic parameters are also examined. Data Sources A search was performed on the PubMed, Cochrane, Scopus, and Web of Science databases up to December 31, 2022. The search strategy was performed using the Medical Subject Heading (MeSH) terms “intermittent fasting” and “gastrointestinal microbiome” and the key words “Ramadan fasting” and “microbes.” Data Extraction Seven human studies (4 TRE and 3 RF) and 9 animal studies (7 TRE, 2 RF-like) were retrieved. Data Analysis TRE and RF in human studies lead to an increase in gut microbial community alpha-diversity. In animal studies (both TRE and RF-like), fasting is not associated with improved alpha-diversity, but enhancement of microbial fluctuation is observed, compared with high-fat diet ad libitum groups. Within Firmicutes and Bacteroidetes phyla, no specific direction of changes resulting from fasting are observed in both animals and human. After TRE or RF, a greater abundance of the Faecalibacterium genus is observed in human studies; changes in Lactobacillus abundance are found in animal studies; and increases in Akkermansia are seen both in humans and in animals fed a feed-pellet diet. Only 2 human studies show a beneficial correlation between microbiota changes and host metabolic (HDL cholesterol) or anthropometric parameters (body mass index). Conclusions These findings support the importance of both regimens in improving the gut microbiota composition. However, based on results of animal studies, it can be suggested that diet remains the essential factor in forming the microbiota’s environment. Systematic Review Registration PROSPERO registration no. CRD42021278918.
Influence of Tempeh, Daidzein, Probiotics, and Their Combination on Magnesium Status and Hematological Ratios in a Postmenopausal Osteoporotic Animal Model
Background/Objectives: Postmenopausal osteoporosis disrupts magnesium homeostasis and hematological balance, contributing to systemic inflammation and metabolic alterations. This study aimed to assess the effects of dietary interventions—tempeh, daidzein, probiotics, and their combinations—on magnesium status and hematological ratios in a postmenopausal osteoporotic Wistar rat model. Methods: Sixty-four rats were divided into one sham group (n = 8) and seven ovariectomized (OVX) groups (n = 56), with different modified diets administered for six weeks. In addition, one of the groups received alendronate bisphosphonate as a pharmacological reference to benchmark the dietary interventions against standard anti-osteoporotic therapy. Magnesium levels in the tissues and feces, along with blood hematological ratios (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and triglyceride-to-glucose index (TyG)), were evaluated. Results: The results revealed that a combination of tempeh and probiotics (OTL) significantly increased magnesium levels in the feces, spleen, and hair, while reducing liver magnesium levels. Compared to the standard groups (S and O), the hematological analysis revealed that the daidzein group (OD) had the highest MLR, while the OTL group exhibited the lowest TyG index. The alendronate bisphosphonate (OB) intervention showed no significant effect on tissue magnesium levels, feces magnesium levels, or hematological ratios. Correlation analysis revealed a strong negative association between spleen magnesium levels and the PLR (r = −0.626) and a positive relationship between liver magnesium levels and TyG (r = 0.422). Conclusions: The authors of this study concludes that while ovariectomy significantly altered magnesium status and hematological ratios, the dietary combination of tempeh, daidzein, and probiotics did not demonstrate an apparent beneficial effect on magnesium status or inflammatory ratios in a postmenopausal osteoporotic rat model. However, the findings highlight interesting aspects of magnesium status and its correlations with metabolic and inflammatory parameters, warranting further investigation.
MOTS-c modulates pancreatic islet function in rats and pigs in vitro
Abstract MOTS-c is a promising regulator of metabolism and energy homeostasis. While its effects have been studied in cell lines, our team aimed to investigate its influence on more complex structures—specifically, isolated pancreatic islets. We used two animal models: the rat, which is commonly studied, and the pig, which shares greater physiological similarities with humans. This study assessed the expression and secretion of insulin and glucagon, the expression of their receptors, cell viability, and cell death following MOTS-c treatment of the islets. Additionally, we examined how MOTS-c secretion is affected by different incubation media, such as the presence of free fatty acids, pancreatic hormones, and different glucose concentrations. The results indicate that MOTS-c impacts pancreatic islet physiology by, for example, reducing insulin and glucagon secretion and enhancing cell viability. Notably, the effects differed between the two species, which may be attributed to anatomical differences in their pancreatic islets or structural variations in rat and pig MOTS-c. These facts may lead to the conclusion that if MOTS-c may be helpful in human medicine, the pig model should be considered another valuable choice.
Cord Blood Spexin Level in Mothers with Obesity—Forecast of Future Obesity?
Spexin (SPX) is a peptide that plays an important role in the regulation of food intake and body weight (BW) by the effect on carbohydrate-lipid metabolism. However, the role of SPX in fetal life, in children, and in adolescent metabolism is limited. Therefore, we decided to check whether obesity affects the concentration of SPX in the mother’s peripheral blood (MB) and umbilical cord blood (UCB). Using MB and UCB sera on the day of delivery obtained from 48 women (24 non-obese and 24 obese) and commercially available Elisa kits and colorimetric assays, we determined changes in SPX and the relationship between SPX concentration and other metabolic and anthropometric markers (body weight and BMI) on the day of delivery and in children at the age of 36 months. We found lower concentrations of SPX in MB (p < 0.05) and UCB (p < 0.01) derived from obese women (BMI > 30) and a moderate linear correlation (r = 0.4429; p < 0.01) between SPX concentrations in MB and UCB. We also noted that the concentration of SPX is not correlated with the child’s body weight on the day of birth (r = −0.0128). However, there is a relationship between SPX at birth and body weight at 3 years of age (r = −0.3219; p < 0.05). Based on the obtained results, it can be assumed that spexin is one of the factors modulating the child’s metabolism already in the fetal period and can be considered a potential marker of future predisposition to obesity. However, confirmation of this thesis requires additional research.
MOTS-c regulates pancreatic alpha and beta cell functions in vitro
AbstractThe aim of this study is to determine the influence of the mitochondrial open-reading-frame of the twelve S rRNA-c (MOTS-c) peptide on pancreatic cell physiology. Moreover, in this study, we examined the changes in MOTS-c secretion and expression under different conditions. Our experiments were conducted using laboratory cell line cultures, specifically the INS-1E and αTC-1 cell lines, which represent β and α pancreatic cells, respectively. As the pancreas is an endocrine organ, we also tested its hormone regulation capabilities. Furthermore, we assessed the secretion of MOTS-c after incubating the cells with glucose and free fatty acids. Additionally, we examined key cell culture parameters such as cell viability, proliferation, and apoptosis. The results obtained from this study show that MOTS-c has a significant impact on the physiology of pancreatic cells. Specifically, it lowers insulin secretion and expression in INS-1E cells and enhances glucagon secretion and expression in αTC-1 cells. Furthermore, MOTS-c affects cell viability and apoptosis. Interestingly, insulin and glucagon affect the MOTS-c secretion as well as glucose and free fatty acids. These experiments clearly show that MOTS-c is an important regulator of pancreatic metabolism, and there are numerous properties of MOTS-c yet to be discovered.
Isolation method and characterization of adipocytes as a tool for equine obesity research – In vitro study
Genistein stimulates the viability and prevents myofibroblastic transformation in human trabecular meshwork cells stimulated by TGF-β
SARMs jako modulatory funkcji metabolicznych i stresu oksydacyjnego tkanki tłuszczowej i serca w szczurzym modelu otyłości – badania in vitro i in vivo
MOTS-c Impact on Muscle Cell Differentiation and Metabolism Across Fiber Types
Background/Aims: MOTS-c belongs to a group of mitochondrial peptides involved in metabolic processes in the body. This peptide has garnered increasing attention since its discovery in 2015 because of its potential to ameliorate metabolic parameters in animals with diabetes or insulin resistance. MOTS-c is involved in muscle metabolism; however, little is known about its role in fiber differentiation. Materials: We conducted a study to explore the effect of MOTS-c on cellular processes using the C2C12 and L6 cell lines, representing different metabolic types of muscle fibers. The research methods were real-time PCR, Western blot, and lipid accumulation measurement. Results: >Notably, our investigations revealed that MOTS-c increased the survival of C2C12 cells at doses of 10 and 100 nM (p<0.01) and stimulated the phosphorylation of extracellular signal-regulated kinase within 5 min of incubation (p<0.05). Remarkably, these effects were not observed in L6 cells; however, both cell lines showed a reduced rate of proliferation. Furthermore, MOTS-c promotes the differentiation of C2C12 cells by increasing the expression of muscle regulatory factors, but it does not produce such an effect in L6 cells. Additionally, cells were treated with physiological concentrations of free fatty acids and MOTS-c, unveiling an augmentation in lipid accumulation observed in L6 cells and a decrease in lipid accumulation in C2C12 cells. Conclusion: In conclusion, our findings have suggested a diverse response to MOTS-c depending on the type of muscle fibers, particularly in the domains of survival, cell differentiation, and lipid accumulation.
LEAP2 in Physiology—A Narrative Review
Liver Enriched Antimicrobial Peptide 2 (LEAP2) is a fascinating peptide that has gained significant attention since its discovery in 2003. Initially identified as an antimicrobial peptide, LEAP2 has more recently been found to play a key role in the regulation of energy metabolism. One of the most notable functions of LEAP2 is its interaction with the ghrelin hormone, which is known for stimulating hunger. LEAP2 acts as an inhibitor of ghrelin, thereby reducing food intake and influencing energy balance. The physiological roles of LEAP2 extend beyond appetite suppression. Studies have shown that LEAP2 has an impact on insulin secretion, suggesting its potential involvement in glucose metabolism and possibly insulin sensitivity, which is crucial in managing conditions like type 2 diabetes. Moreover, LEAP2 levels appear to fluctuate based on factors such as gender, developmental stage, and even interventions like bariatric surgery, which is known for its role in managing obesity and diabetes. Given these findings, LEAP2 shows potential as a therapeutic target, particularly for addressing obesity and metabolic diseases such as type 2 diabetes. Its ability to influence food intake and energy balance makes it a promising candidate for further research into therapies aimed at weight regulation and glycemic control. In the future, LEAP2 could become an important agent in the development of treatments aimed at curbing obesity and its associated metabolic disorders.
Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases
Abstract Purpose Selective androgen receptor modulators (SARMs) have demonstrated agonist activity on the androgen receptor in various tissues, stimulating muscle mass growth and improving bone reconstruction. Despite being in clinical trials, none has been approved by the Food and Drug Administration (FDA) or European Medicines Agency for pharmacotherapy. Still, SARMs are very popular as performance-enhancing drugs. The FDA has issued warnings about the health risks associated with SARMs, but the long-term exposure and possible adverse events still need to be fully understood. This review aims to evaluate the adverse events associated with using SARMs by humans. Methods PubMed database was searched from September 16, 2022, to October 2, 2023. In total, 20 records were included in the final review. Data from preclinical and clinical studies supported the review. Results Since 2020, 20 reports of adverse events, most described as drug-induced liver injury associated with the use of SARM agonists, have been published. The main symptoms mentioned were cholestatic or hepatocellular liver injury and jaundice. Limited data are related to the dosages and purity of SARM supplements. Conclusion Promoting SARMs as an anabolic agent in combination with other performance-enhancing drugs poses a risk to users not only due to doping controls but also to health safety. The lack of quality control of consumed supplements makes it very difficult to assess the direct impact of SARMs on the liver and their potential hepatotoxic effects. Therefore, more detailed analyses are needed to determine the safety of using SARMs.