ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.
ABSTRACT
The objective of this study was to determine the concentrations of calcium,phosphorus and magnesium in blood and compare the differences in seven areas of Heilongjiang province,and then estimate calcuim-phosphorus metabolism of beef cattle in seven beef cattle farms to provi detheoretical foundation for the prevention of calcium phosphorus metabolism diseases of beef cattle.Seven beef cattle farms of Daqing,Shuangyashan,Jiusan and Mudanjiang in Heilongjiang province were selected as the survey sites,which were recorded as group A (both grazing and stall-feeding in Shuangyashan),group B (stall-feeding mode in Shuangyashan),group C (stall-feeding mode in Daqing),group D (grazing mode in Jiusan),group E (both grazing and stall-feeding in Daqing),group F (both grazing and stall-feeding in Daqing) and group G (stall-feeding mode in Mudanjiang).Then the concentrations of Ca,Mg,P,free fatty acid (NEFA),glucose (Glc) and β-hydroxybutyric acid (BHBA) in the blood were compared to estimate the calcuim-phosphorus metabolic states.Results showed that the concentrations of calcium,magnesium and phosphorus in the plasma of 65 beef cattle in seven survey sites were within the normal range,and there was no significant difference in calcium concentration among seven sites.The P contents in group C and G were significantly higher those that in group A and B(P＜0.01),which in group C was significantly higher than those in group D,E and F (P＜0.01),which in group G was significantly higher than those in group D,E and F(P＜0.01).NEFA content in group B was significantly higher than that in group D (P＜0.05),and there was no difference among other groups.The concentration of Glc in group A was significantly higher than that in group E (P＜0.05),which in group B was significantly higher than those in group A and D,and was very significantly higher than those in group E,F and G (P＜0.01),which in group C was very significantly higher than those in group A,D,E,F and G (P＜0.01),which in group C was significantly higher than those in group A,D,E,F and G (P＜0.01),which in group D was significantly higher than that in group E (P＜0.05),and which in group F was significantly higher than that in group E (P＜0.05).The concentration of BHBA in group C,D and E were significantly higher than that in group A (P＜0.01),which in group C was significantly higher than that in group B (P＜0.05),which in group D and E was significantly higher than that in group B (P＜0.01),which in group C was significantly higher than that in group G (P＜0.01),which in group D was significantly higher than those in group F and G (P＜0.01),and in group E was highly significantly higher than that in group F and G (P＜0.01).Overall,there were not calcuim-phosphorus metabolic disorders within the seven beef cattle farms which were selected,but it is also necessary to strengthen feeding management and health care to prevent the occurrence of nutrition and metabolic diseases.
ABSTRACT
Biochemical indexes and blood composition in early lactation health,ketosis and hypocalcemia dairy cows were analyzed to make sure the milk composition characteristics with related diseases,the correlation analysis between early lactating dairy milk composition and blood biochemical were also make in order to provide support for the cattle health assessment.According to theblood index,72 Holstein cows 7-21 d postpartum,were divided into group subclinical hypocalcemia,ketosis test group and control group,24 heads each group.The blood and milk of cows were collected and used to analyze the correlation between blood biochemical indexes and milk composition.The results showed that ketosis and hypocalcemia induced the level of milk protein and non fat milk solids decreased,while the content of citric acid in milk increased.The correlation equation between citric acid in milk and serum NEFA,BHBA and GLU was y=3.192x-0.802,(R2 =0.363),y=4.594x-0.793,(R2 =0.320),y=1.228x+0.775,(R2 =0.261),in which x was the content of citric acid in milk.The results showed that the content of citric acid in milk had positively related to blood NEFA,which could be used as an early marker for the diagnosis of negative energy balance.The levels of BUN and ALB in blood can be used to evaluate the levels of milk protein and urea.