Spexin (SPX) is a 14 aa peptide discovered in 2007 using bioinformatics methods. SPX inhibits food intake and regulates lipid, and carbohydrate metabolism. Here, we evaluate the ability of SPX at improving metabolic control and liver function in obese and type 2 diabetic animals. The effects of 30 days SPX treatment of mice with experimentally induced obesity (DIO) or type 2 diabetes (T2DM) on serum glucose and lipid levels, insulin sensitivity and hormonal profile (insulin, glucagon, adiponectin, leptin, TNF alpha, IL-6 and IL-1β) are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. We report that SPX decreases body weight in healthy and DIO mice, and reduces lipid content in all three animal groups. SPX improves insulin sensitivity in DIO and T2DM animals. In addition, SPX modulates hormonal and metabolic profile by regulating the concentration of adiponectin (concentration increase) and leptin (concentration decrease) in the serum blood of DIO and T2DM mice. Lastly, SPX decreases lipid content as well as IL-6 and TNF-α protein levels in liver of DIO and T2DM mice, and reduces IL-6 and TNF-alpha concentrations in the serum derived from T2DM mice. Based on our results, we conclude that SPX could be involved in the development of obesity and type 2 diabetes mellitus and it can be further evaluated as a potential target for therapy of DIO and T2DM.

Elderberry (Sambucus nigra L.) lipophilic and polar extract dietary supplementation effects were evaluated according to diabetes management indices, using an in vivo model. A research pipeline was constructed, that ranged from extract preparation, partial chemical characterization and toxicity evaluation, to examining the elderberry extract dietary supplementation effects on biofluid and tissues. Extracts toxicity was screened using an Aliivibrio fischeri bioluminescence model. A concentration of up to 60 mg/L was selected, and rat doses for oral supplementation were computed applying the interspecies correlation between A. fischeri and rats. Wistar type 2 diabetic rats, induced by streptozotocin (STZ), were fed a high-fat diet and supplemented for 4 weeks at doses of 190 and 350 mg/kg body weight/day of lipophilic and polar extract, respectively. As far as we know, lipophilic elderberry extract supplementation was assessed for the first time, while polar extract was administrated at higher doses and for a shorter period compared to previous studies, aiming to evaluate subacute supplementation effects. The polar extract modulated glucose metabolism by correcting hyperglycemia, while the lipophilic extract lowered insulin secretion. Both extracts lowered insulin resistance, without remarkable alterations to hematological indices, sera lipids and sera and tissular trace element homeostasis. In conclusion, elderberries are a potential source of bioactive compounds for formulations to be used as co-adjuvants in diabetes management.

Peptide hormones play a prominent role in controlling energy homeostasis and metabolism. They have been implicated in controlling appetite, the function of the gastrointestinal and cardiovascular systems, energy expenditure, and reproduction. Furthermore, there is growing evidence indicating that peptide hormones and their receptors contribute to energy homeostasis regulation by interacting with white and brown adipose tissue. In this article, we review and discuss the literature addressing the role of selected peptide hormones discovered in the 21st century (adropin, apelin, elabela, irisin, kisspeptin, MOTS-c, phoenixin, spexin, and neuropeptides B and W) in controlling white and brown adipogenesis. Furthermore, we elaborate how these hormones control adipose tissue functions in vitro and in vivo.

SPX (spexin) and its receptors GalR2 and GalR3 (galanin receptor subtype 2 and galanin receptor subtype 3) play an important role in the regulation of lipid and carbohydrate metabolism in human and animal fat tissue. However, little is still known about the role of this peptide in the metabolism of muscle. The aim of this study was to determine the impact of SPX on the metabolism, proliferation and differentiation of the skeletal muscle cell line C2C12. Moreover, we determined the effect of exercise on the SPX transduction pathway in mice skeletal muscle. We found that increased SPX, acting via GalR2 and GalR3 receptors, and ERK1/2 phosphorylation stimulated the proliferation of C2C12 cells (p < 0.01). We also noted that SPX stimulated the differentiation of C2C12 by increasing mRNA and protein levels of differentiation markers Myh, myogenin and MyoD (p < 0.01). SPX consequently promoted myoblast fusion into the myotubule (p < 0.01). Moreover, we found that, in the first stage (after 2 days) of myocyte differentiation, GalR2 and GalR3 were involved, whereas in the last stage (day six), the effect of SPX was mediated by the GalR3 isoform. We also noted that exercise stimulated SPX and GalR2 expression in mice skeletal muscle as well as an increase in SPX concentration in blood serum. These new insights may contribute to a better understanding of the role of SPX in the metabolism of skeletal muscle.

MOTS-c peptide is a member of the group of mitochondria-derived peptides (MDP). It is a product of the open reading frame in the 12S RNA gene. Due to its features and functions in the body, this peptide is classified as a hormone. The first publications indicated that this hormone improves insulin sensitivity and lowers body weight in obese animals. This suggests that it may be an important peptide in maintaining the body’s energy homeostasis. The aim of our work was to investigate the potential role of MOTS-c peptide during pregnancy, which is a condition prone to metabolic disorders. The research covered healthy, obese women and women with thyroid disorders. The obtained results indicated an increase in the concentration of MOTS-c in the blood of mothers and newborns in the obese group as compared to the healthy control group and a corresponding decrease in the concentration of this peptide in mothers and newborns in the group with hypothyroidism compared to the obese group. Moreover, we also observed a strong positive correlation between the concentration of MOTS-c in maternal blood and in umbilical cord blood. In summary, the MOTS-c peptide shows changes in blood concentration in various physiological states and may, in the future, become an important tool in the fight against metabolic diseases such as obesity or type 2 diabetes.