Excessive lipid deposition in layer chickens due to inappropriate feeding adversely affects egg production; however, nutritional manipulation methods to deal with this issue are still limited. β-hydroxy-β-methylbutyrate (HMB), a metabolite of L-leucine, was recently reported as a lipid-lowering nutrient in mice and pigs, although its role in layers had not been investigated. Here, we employed high-fat and high-cholesterol diet (HFHCD)−challenged growing layers as an obese model to explore HMB function in the regulation of lipid metabolism and the potential mechanisms involved. We found that dietary supplementation with (0.05% or 0.10%) HMB significantly reduced HFHCD−induced bodyweight growth in layers, mainly due to reduction in abdominal fat deposition. Mechanistically, HMB supplementation enhanced hepatic bile acid synthesis from cholesterol through elevating expression of Cyp7a1, a gene coding a key enzyme in bile acid synthesis. Furthermore, 16S rRNA gene sequencing revealed that HMB supplementation remodeled the diversity and composition of the layers’ cecal microbiota, and the abundance of Bacteroidetes at the phylum level were especially affected. Correlation analysis further indicated a strong negative association between Bacteroidetes abundance and lipid metabolism−related parameters. Taken together, these data suggest that dietary HMB supplementation could improve abdominal fat deposition in layers, probably through modulating hepatic bile acid synthesis and gut microbiota function.

Excessive abdominal fat deposition in chickens is a major concern in the poultry industry. Nutritional interventions are a potential solution, but current options are limited. Asiaticoside (Asi), a herbal extract, has shown positive effects in animals, but its impact on poultry lipid metabolism is still unknown. In this study, the effects of dietary Asi on yellow-feathered chicken lipid metabolism and its potential mechanisms were investigated. A total of 120 chickens were randomly divided into three groups, with five replicates per group and 8 chickens per replicate. The chickens were fed a basal diet supplemented with 0, 0.01, or 0.05% Asi for 6 wk. The results showed that Asi down-regulated lipogenic gene expression and up-regulated lipid-breakdown-related genes in both the liver and fat tissues of the chickens, which resulted in a half reduction in abdominal fat while not affecting meat yield. Mechanistically, the hepatic and adipose PI3K/AKT pathway may be involved in Asi-induced fat loss in chickens as revealed by computer-aided reverse drug target prediction and gene expression analysis. Moreover, Asi ingestion also significantly modified the cecal microbiota of the chickens, resulting in a reduced Firmicutes to Bacteroidetes ratio and decreased abundance of bacteria positively correlated with abdominal fat deposition such as Ruminococcus, while increasing the abundance of bacteria inversely correlated with abdominal fat deposition such as Lactobacillus, Bacteroides, and Blautia. Collectively, these data suggest that Asi could ameliorate the abdominal fat deposition in yellow-feathered chickens, probably through modulating the PI3K/AKT pathway and gut microbiota function.

Eukaryotic elongation factor 2 kinase (eEF2K) is a highly conserved α kinase and is increasingly considered as an attractive therapeutic target for cancer as well as other diseases. However, so far, no selective and potent inhibitors of eEF2K have been identified. In this study, pharmacophore screening, homology modeling, and molecular docking methods were adopted to screen novel inhibitor hits of eEF2K from the traditional Chinese medicine database (TCMD), and then cytotoxicity assay and western blotting were performed to verify the validity of the screen. Resultantly, after two steps of screening, a total of 1077 chemicals were obtained as inhibitor hits for eEF2K from all 23,034 compounds in TCMD. Then, to verify the validity, the top 10 purchasable chemicals were further analyzed. Afterward, Oleuropein and Rhoifolin, two reported antitumor chemicals, were found to have low cytotoxicity but potent inhibitory effects on eEF2K activity. Finally, molecular dynamics simulation, pharmacokinetic and toxicological analyses were conducted to evaluate the property and potential of Oleuropein and Rhoifolin to be drugs. Together, by integrating in silico screening and in vitro biochemical studies, Oleuropein and Rhoifolin were revealed as novel eEF2K inhibitors, which will shed new lights for eEF2K-targeting drug development and anticancer therapy.