Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation / 医学前沿

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.

Regulation of organic nucleic acids and serum biochemistry parameters by dietary chromium picolinate supplementation in swine model.

The relationships between chromium and metabolism are sophisticated. Organic nucleic acids and serum biochemistry parameters are affected by dietary chromium levels. The objective of this work was to study the effect of chromium picolinate (CrPic) supplementation on total DNA and RNA contents, the ratio of RNA/DNA in muscle and in pancreatic tissue, the level of insulin receptor (IR) mRNA and some serum biochemistry parameters in a porcine model. Young animals (48) were assigned randomly into three groups of 16 piglets, fed with three different dietary levels of Cr (common basal feedstuff alone or supplemented with CrPic at a dose of 1.61 µg/g or 3.22 µg/g, which corresponds to 0.2 µg/g and 0.4 µg/g Cr). After 80 days, the animals were sacrificed and skeletal muscle and pancreatic tissues were analyzed to detect differences caused by different levels of dietary Cr. The total content of RNA in muscle was increased significantly (P<0.05) in the CrPic supplemented groups. There was no significant difference between groups in the concentrations of total RNA in the pancreas or DNA in the muscle and pancreatic tissues. The RNA/DNA ratio in pancreas showed no significant change but the ratio was increased significantly (P<0.05) in muscle. There was a slight increase of the mRNA level of IR but there was no significant difference between groups. The content of serum cholesterol and insulin were reduced significantly (P<0.05) in the CrPic-supplemented groups and the content of high-density lipoprotein cholesterol (HDLC) was increased significantly (P<0.05) as the CrPic dose increased. There was a slight (non-significant) reduction of the concentrations of serum triglyceride and low-density lipoprotein cholesterol (LDLC) in the CrPic supplementation groups. Supplementary CrPic caused no significant change of muscular mRNA level of IR in healthy animals. An increased content of RNA in muscle, improved cholesterol metabolism and improved insulin sensitivity were found in these CrPic-treated groups in the porcine model.

EFFECTS OF SELENIUM-AND ZINC-ENRICHED PROBIOTICS ON BLOOD CONTENT OF SELENIUM AND ZINC,ANTIOXIDATION FUNCTION AND INTESTINAL MICROFLORA IN CANINES / 营养学报

Objective To investigate the effects of selenium-and zinc-enriched probiotics on the content of selenium and zinc in blood,antioxidation function and intestinal microflora in canine.Method Eight 18-month native canines,female and male in half,were randomly divided into the control and treatment groups on average.The control group received basal diet,the treatment group received basal diet supplemented with 2.0g selenium-and zinc-enriched probiotics everyday.To determine the experimental indices,the samples were collected on D0,D15 and D30,respectively.Results Compared with the control group,on D15,the content of selenium and zinc in blood,blood GPX,serum SOD,T-AOC and the amount of Lactobacillus in the experimental group were significantly increased,while the amount of Escherichia coli significantly decreased,but the serum MDA and the amount of Bifidobacterium,Staphylococcus and Enterococcus had no significant change.On D30,the content of selenium in blood,serum SOD,T-AOC and the amount of Lactobacillus were very significantly increased,while the content of zinc in blood,blood GPX and the amount of Bifidobacterium significantly increased;but serum MDA and the amount of Escherichia coli,Staphylococcus and Enterococcus very significantly decreased.Conclusion Selenium-and zinc-enriched probiotics could increase content of selenium and zinc in blood,enhance antioxidation function,improve and regulate the intestinal microflora.