Intestinal melatonin levels and gut microbiota homeostasis are independent of the pineal gland in pigs.

Introduction: Melatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model to investigate the functions of pineal MEL and its relationship with various diseases. However, the effect of PINX on the gastrointestinal tract (GIT) MEL levels and gut microbiome in pigs has not been previously reported. Methods: By using a newly established pig PINX model, we detected the levels of MEL in the GIT by liquid chromatography-tandem mass spectrometry. In addition, we examined the effects of PINX on the expression of MEL synthesis enzymes, intestinal histomorphology, and the intestinal barrier. Furthermore, 16S rRNA sequencing was performed to analyze the colonic microbiome. Results: PINX reduced serum MEL levels but did not affect GIT MEL levels. Conversely, MEL supplementation increased MEL levels in the GIT and intestinal contents. Neither PINX nor MEL supplementation had any effect on weight gain, organ coefficient, serum biochemical indexes, or MEL synthetase arylalkylamine N-acetyltransferase (AANAT) expression in the duodenum, ileum, and colon. Furthermore, no significant differences were observed in the intestinal morphology or intestinal mucosal barrier function due to the treatments. Additionally, 16S rRNA sequencing revealed that PINX had no significant impact on the composition of the intestinal microbiota. Nevertheless, MEL supplementation decreased the abundance of Fibrobacterota and increased the abundance of Actinobacteriota, Desulfobacterota, and Chloroflexi. Conclusion: We demonstrated that synthesis of MEL in the GIT is independent of the pineal gland. PINX had no influence on intestinal MEL level and microbiota composition in pigs, while exogenous MEL alters the structure of the gut microbiota.

Hepatoprotective Effects of Taurine Against Cadmium-Induced Liver Injury in Female Mice.

Cadmium (Cd), a heavy metal contaminant, seriously threatens human and animal health. Taurine (Tau) has been used against hepatotoxicity caused by different environmental toxins. However, it has not been elucidated whether Tau exerts its protective function against Cd-induced hepatotoxicity. The aim of this study was thus to evaluate the ameliorative function of Tau (500 mg/kg body weight intraperitoneally) on Cd-induced (2 mg/kg body weight intraperitoneally) liver toxicity in mice for 14 days. The histopathologic and ultrastructure changes as well as alterations in indexes related to liver function, antioxidant biomarkers, inflammatory, and apoptosis were evaluated. The results showed that Tau alleviated the vacuolar degeneration, nuclear condensation, mitochondria swelling, and cristae lysis of hepatocytes induced by Cd. In addition, Tau treatment significantly reduced the ALT, AST levels in serum, and inflammatory factor TNF-α and IL-1ß in liver tissue. Furthermore, Tau treatment decreased the Bax/Bcl-2 ratio and cleaved caspase-3 protein expression levels. Taken together, these observations demonstrate that Tau has an important hepatic protective function against the inflammation and apoptosis induced by Cd.

Casein kinase 1α is required to maintain murine hypothalamic pro-opiomelanocortin expression.

Hypothalamic pro-opiomelanocortin (POMC) neuron development is considered to play an essential role in the development of obesity. However, the underlying mechanisms remain unclear. Casein kinase 1α (CK1α) was expressed in the embryonic mouse hypothalamus at high levels and colocalized with POMC neurons. CK1α deletion in POMC neurons caused weight gain, metabolic defects, and increased food intake. The number of POMC-expressing cells was considerably decreased in Csnk1a1fl/fl;POMCcre (PKO) mice from embryonic day 15.5 to postnatal day 60, while apoptosis of POMC neurons was not affected. Furthermore, unchanged POMC progenitor cells and a decreased POMC phenotype established CK1α function in hypothalamic POMC neuron development. CK1α deletion led to elevated Notch intracellular domain (NICD) protein expression, and NICD inhibition rescued the PKO mouse phenotype. In summary, CK1α is involved in hypothalamic POMC expression via NICD-POMC signaling, deepening our understanding of POMC neuron development and control of systemic metabolic functions.