The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity.

Thimet oligopeptidase (EC 3.4.24.15; EP24.15; THOP1) is a potential therapeutic target, as it plays key biological functions in processing biologically functional peptides. The structural conformation of THOP1 provides a unique restriction regarding substrate size, in that it only hydrolyzes peptides (optimally, those ranging from eight to 12 amino acids) and not proteins. The proteasome activity of hydrolyzing proteins releases a large number of intracellular peptides, providing THOP1 substrates within cells. The present study aimed to investigate the possible function of THOP1 in the development of diet-induced obesity (DIO) and insulin resistance by utilizing a murine model of hyperlipidic DIO with both C57BL6 wild-type (WT) and THOP1 null (THOP1-/-) mice. After 24 weeks of being fed a hyperlipidic diet (HD), THOP1-/- and WT mice ingested similar chow and calories; however, the THOP1-/- mice gained 75% less body weight and showed neither insulin resistance nor non-alcoholic fatty liver steatosis when compared to WT mice. THOP1-/- mice had increased adrenergic-stimulated adipose tissue lipolysis as well as a balanced level of expression of genes and microRNAs associated with energy metabolism, adipogenesis, or inflammation. Altogether, these differences converge to a healthy phenotype of THOP1-/- fed a HD. The molecular mechanism that links THOP1 to energy metabolism is suggested herein to involve intracellular peptides, of which the relative levels were identified to change in the adipose tissue of WT and THOP1-/- mice. Intracellular peptides were observed by molecular modeling to interact with both pre-miR-143 and pre-miR-222, suggesting a possible novel regulatory mechanism for gene expression. Therefore, we successfully demonstrated the previously unanticipated relevance of THOP1 in energy metabolism regulation. It was suggested that intracellular peptides were responsible for mediating the phenotypic differences that are described herein by a yet unknown mechanism of action.

Nutraceutical Potential of Carica papaya in Metabolic Syndrome.

Carica papaya L. is a well-known fruit worldwide, and its highest production occurs in tropical and subtropical regions. The pulp contains vitamins A, C, and E, B complex vitamins, such as pantothenic acid and folate, and minerals, such as magnesium and potassium, as well as food fibers. Phenolic compounds, such as benzyl isothiocyanate, glucosinolates, tocopherols (α and δ), ß-cryptoxanthin, ß-carotene and carotenoids, are found in the seeds. The oil extracted from the seed principally presents oleic fatty acid followed by palmitic, linoleic and stearic acids, whereas the leaves have high contents of food fibers and polyphenolic compounds, flavonoids, saponins, pro-anthocyanins, tocopherol, and benzyl isothiocyanate. Studies demonstrated that the nutrients present in its composition have beneficial effects on the cardiovascular system, protecting it against cardiovascular illnesses and preventing harm caused by free radicals. It has also been reported that it aids in the treatment of diabetes mellitus and in the reduction of cholesterol levels. Thus, both the pulp and the other parts of the plant (leaves and seeds) present antioxidant, anti-hypertensive, hypoglycemic, and hypolipidemic actions, which, in turn, can contribute to the prevention and treatment of obesity and associated metabolic disorders.

Extruded urea could reduce true protein source in beef cattle diets.

Rumen micro-organisms are capable of producing microbial protein from ammonia and carbon skeleton, and non-protein nitrogen (NPN) may be one of the sources of ammonia. Alternative source of NPN is the slow release of ammonia sources in which the product is the extrusion of starch with urea. This work aimed to determine the effects on nutrient intake, ingestive behaviour, digestibility, nitrogen balance, ruminal pH, rumen ammonia nitrogen, volatile fatty acids (VFA) and blood parameters with increased levels of extruded urea (50, 60, 70 and 80 g/100 kg of body weight [BW]) in beef cattle diet. Four rumen cannulated crossbred steers with initial mean weight of 336 ± 47 kg in a 4 × 4 Latin square design were distributed. Diets were formulated with 400:600 g/kg roughage:concentrate ratio on dry matter based and provided once per day, being used whole corn silage as roughage. There were no effects on nutrient intake (kg/day), ingestive behaviour, apparent digestibility, nitrogen balance, volatile fatty acid (VFA) and blood parameters in extruded urea treatment groups. Similar results were observed on time spent on feeding, rumination and idleness. There were positive linear effects (p = 0.022) on rumen pH in the time of 8 hr after feeding and also on plasma concentration of the extruded urea levels (p = 0.039); whereas a linear negative effect (p = 0.030) was observed on ammonia nitrogen for the collection time of 2 hr after feeding. Increased levels of extruded urea could maintain nutrient intake, digestibility, ingestive behaviour, rumen pH and blood parameters in normal conditions. In conclusion, we recommend the extruded urea use with values up to 80 g/100 kg BW in confined beef cattle that receive balanced diets with 140 g/kg of crude protein.