The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial

High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation

The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial

High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation

The molecular mechanism of interaction of Et3Pb+ with tubulin

Triethyllead ion (Et3Pb+) was found to interact with 2 out of 18 thiol groups present in tubulin dimers. Specificity of the interaction was shown by the high affinity of Et3Pb+ to tubulin, by the fact that the 16 residual thiol groups in tubulin remained unaffected, and by the observation that other proteins with exposed thiol groups, e.g., actin, did not react with Et3Pb+. After complexation of the two thiol groups, tubulin in vitro had lost its capability for microtubule assembly. Likewise, polymerized tubulin disassembled on addition of the lead compound

In vitro formation of different tubulin polymers from purified tubulin of ehrlich ascites tumor cells.

AbstractPreparations of cycled tubulin from Ehrlich ascites tumor cells contain several acessory proteins; once or twice cycled microtubule preparations are usually composed of fibers 10 nm in diameter, but lack vimentin. Highly purified tubulin consists of α- and β-tubulin and a minor component which was identified by peptide mapping as a second β-chain. This pure tubulin is able to form in vitro at low concentrations (1 mg protein/ml) fibers of about 10 nm width, and at higher concentrations (3.5 mg protein/ml) normal microtubules

High cytotoxicity and membrane permeability of Et3Pb+ in mammalian and plant cells

Cells of mammalian origin as well as those of higher plants appear to be very sensitive to triethyllead ion (Et3Pb+). Neuroblastoma cells kept in the presence of 1 μM Et3Pb+ lost their viability within 6 h. Growth of suspension culture cells of soybean (G. max (L.)Merr.) was inhibited by 1 μM Et3Pb+, and finally the cells died. Morphologically, Et3Pb+ caused the complete breakdown of microtubular structures in neuroblastoma cells; thus microtubules appeared to be the main target for the toxin. While in a previous study the effect of Et3Pb+ on microtubules has been well documented at concentrations of 50–200 μM 1, the present study demonstrates that the formation of microtubules from pig brain tubulin is disturbed at concentrations of Et3Pb+ as low as 0.5 to 1 μM . We conclude from these data that Et3Pb+ freely permeates the plasma membranes of mammalian as well as plant cells