High concentrations of fatty acids and ß-hydroxybutyrate impair the growth hormone-mediated hepatic JAK2-STAT5 pathway in clinically ketotic cows.

The hepatic growth hormone (GH)-insulin-like growth factor (IGF)-I axis is essential for regulating intrahepatic lipid metabolism. Ketotic cows are characterized by high blood concentrations of fatty acids and ß-hydroxybutyrate (BHB), which display lipotoxicity. The aim of this study was to investigate changes in the hepatic GH-IGF-I axis in ketotic cows and to determine the effects of fatty acids and BHB on the GH-IGF-I axis in calf hepatocytes. Liver and blood samples were collected from healthy (n = 15) and clinically ketotic (n = 15) cows. Hepatocytes were isolated from calves and treated with various concentrations of GH, fatty acids, and BHB. The results showed that clinically ketotic cows displayed a high blood concentration of GH, a low blood concentration of IGF-I, and decreased hepatic GHR1A expression as well as impaired hepatic Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling. In vitro, GH treatment induced activation of the JAK2-STAT5 pathway to increase the mRNA expression and secretion of IGF-I in calf hepatocytes. More importantly, treatment with fatty acids or BHB significantly inhibited GHR1A mRNA and JAK2 protein expression, as well as the STAT5 phosphorylation level and phospho-STAT5 nuclear translocation; these effects markedly reduced IGF1 mRNA expression and secretion in calf hepatocytes. In summary, these results indicate that high blood concentrations of fatty acids or BHB can impair the intrahepatic GH-mediated JAK2-STAT5 pathway and downregulate IGF-I expression and secretion in ketotic cows.

Assessment of the antidiarrhoeal properties of the aqueous extract and its soluble fractions of Chebulae Fructus (Terminalia chebula fruits).

Context Chebulae Fructus is used as an herbal remedy for diarrhoea in traditional Chinese medicine. However, there is no scientific evidence to support its antidiarrhoeal activity. Objective This study evaluates the antidiarrhoeal properties of Chebulae Fructus aqueous extract (CFAE) and determines the active fraction. Materials and methods The antidiarrhoeal effect of CFAE (200-800 mg/kg) was investigated by determining the wet dropping, intestinal transit in BALB/c mice and enteropooling in Wister rats. The protective effects of the CFAE on the intestinal and liver were tested by histopathological analyses. The antidiarrhoeal fraction was determined by castor oil-induced diarrhoea and its main constituents were identified by HPLC-ESI-MS. Results The extract at doses of 200, 400 and 800 mg/kg reduced the diarrhoea by 9.1, 40.0 and 58.2% and inhibited intestinal transit by 18.3, 24.1 and 35.7%, respectively. Additionally, the CFAE (200, 400 and 800 mg/kg) decreased the volume of enteropooling by 47.1, 58.8 and 64.7%, respectively. Mice treated with castor oil presented morphological alterations in the small intestine and the liver. However, the lesions of mice treated with CFAE were alleviated. Moreover, the ethyl acetate fraction was the active fraction of CFAE, the fraction (41.7, 83.4 and 166.8 mg/kg) reduced the diarrhoea by 9.1, 38.2 and 54.5%, respectively. The major components of the ethyl acetate fraction were tannins, including gallic acid, 3, 4, 6-tri-O-galloyl-ß-d-Glc, corilagin and ellagic acid according to the HPLC-ESI-MS analysis. Conclusion The CFAE possessed antidiarrhoeal property and the ethyl acetate fraction was its main active fraction.

GPCR-mediated regulation of beige adipocyte formation: Implications for obesity and metabolic health.

Obesity and its associated complications pose a significant burden on health. The non-shivering thermogenesis (NST) and metabolic capacity properties of brown adipose tissue (BAT), which are distinct from those of white adipose tissue (WAT), in combating obesity and its related metabolic diseases has been well documented. However, beige adipose tissue, the third and relatively novel type of adipose tissue, which emerges in extensive presence of WAT and shares similar favorable metabolic properties with BAT, has garnered considerable attention in recent years. In this review, we focused on the role of G protein-coupled receptors (GPCRs), the largest receptor family and the most successful class of drug targets in humans, in the induction of beige adipocytes. More importantly, we highlight researchers' clinical treatment attempts to ameliorate obesity and other related metabolic diseases through the formation and activation of beige adipose tissue. In summary, this review provides valuable insights into the formation of beige adipose tissue and the involvement of GPCRs, based on the latest advancements in scientific research.