LEAP2 in Physiology—A Narrative Review
2025, Sosinski, Oskar, Pruszyńska-Oszmałek, Ewa, Leciejewska, Natalia, Sassek, Maciej, Kołodziejski, Paweł Antoni
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.
MOTS-c regulates pancreatic alpha and beta cell functions in vitro
2024, Bień, Jakub, Pruszyńska-Oszmałek, Ewa, Kołodziejski, Paweł Antoni, Leciejewska, Natalia, Szczepankiewicz, Dawid, Sassek, Maciej
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
2025, Kołodziejski, Paweł Antoni, Leciejewska, Natalia, Sassek, Maciej, Nogowski, Leszek, Szumacher, Małgorzata, Mikuła, Robert, Gogulski, Maciej, Pruszyńska-Oszmałek, Ewa
MOTS-c Impact on Muscle Cell Differentiation and Metabolism Across Fiber Types
2025, Leciejewska, Natalia, Pruszyńska-Oszmałek, Ewa, Kołodziejski, Paweł Antoni, Szczepankiewicz, Dawid, Nogowski, Leszek, Sassek, Maciej
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.
Rola mitochondrialnego peptydu MOTS-c w funkcjonowaniu trzustki i tkanki tłuszczowej
MOTS-c modulates pancreatic islet function in rats and pigs in vitro
2025, Bień, Jakub, Pruszyńska-Oszmałek, Ewa, Kołodziejski, Paweł, Leciejewska, Natalia, Szczepankiewicz, Dawid, Grzęda, Emilia, Sassek, Maciej
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.
Impact of Lactobacillus acidophilus and Its Combination with Isoflavone Products on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in a Post-Menopausal Osteoporotic Rat Model
2024, Harahap, Iskandar Azmy, Schmidt, Marcin, Pruszyńska-Oszmałek, Ewa, Sassek, Maciej, Suliburska, Joanna
Osteoporosis in menopausal women requires alternatives to current medications, considering their adverse effects. In this context, probiotics and isoflavone products are promising dietary interventions. The objective of our study was to examine the impacts of Lactobacillus acidophilus and its combination with daidzein and tempeh on calcium status, calcium transporters, and bone metabolism biomarkers in a post-menopausal osteoporotic rat model. A total of 48 female Wistar rats were exposed to a two-stage experiment involving calcium deficit induction and subsequent dietary interventions across six groups. Calcium levels, the gene expression of TRPV5 and TRPV6 calcium transporters, bone histopathology, serum bone metabolism markers, and blood biochemistry were evaluated. The results revealed that, while decreasing serum calcium levels, the groups that received the probiotic L. acidophilus and isoflavone combination exhibited increased bone metabolism biomarkers and decreased calcium transporter expressions, akin to the effects of bisphosphonate. Additionally, significant improvements in bone histopathology were observed in these groups. However, the group receiving probiotic L. acidophilus alone did not exhibit significant changes in bone resorption biomarkers, calcium transporter expression, or various blood parameters. Meanwhile, the combination of probiotic L. acidophilus with tempeh positively influenced hematological parameters and reduced cholesterol and triglyceride levels, but it led to elevated blood glucose levels. Correlation analyses highlighted associations between serum calcium levels, calcium transporter expression, and bone metabolism biomarkers. In conclusion, our findings suggest that the daily consumption of probiotic L. acidophilus in combination with isoflavone products may improve bone health in ovariectomized rats, warranting further research to elucidate potential interactions with other nutrients.