ABSTRACT
The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as γ-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.
Subject(s)
Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Insulin Resistance , Metabolic Syndrome/therapy , Blood Glucose/analysis , Blood Glucose/metabolism , Fecal Microbiota Transplantation/methods , Feces/microbiology , Humans , Male , Metabolic Syndrome/blood , Metabolic Syndrome/metabolism , Metabolic Syndrome/microbiology , Middle Aged , Transplantation, Autologous/methods , Transplantation, Homologous/methods , gamma-Aminobutyric Acid/blood , gamma-Aminobutyric Acid/metabolismABSTRACT
Excess dietary long-chain fatty acid (LCFA) intake results in ectopic lipid accumulation and insulin resistance. Since medium-chain fatty acids (MCFA) are preferentially oxidized over LCFA, we hypothesized that diets rich in MCFA result in a lower ectopic lipid accumulation and insulin resistance compared to diets rich in LCFA. Feeding mice high-fat (HF) (45% kcal fat) diets for 8 weeks rich in triacylglycerols composed of MCFA (HFMCT) or LCFA (HFLCT) revealed a lower body weight gain in the HFMCT-fed mice. Indirect calorimetry revealed higher fat oxidation on HFMCT compared to HFLCT (0.011.0±0.0007 vs. 0.0096±0.0015 kcal/g body weight per hour, P<.05). In line with this, neutral lipid immunohistochemistry revealed significantly lower lipid storage in skeletal muscle (0.05±0.08 vs. 0.30±0.23 area%, P <.05) and in liver (0.9±0.4 vs. 6.4±0.8 area%, P<.05) after HFMCT vs. HFLCT, while ectopic fat storage in low fat (LF) was very low. Hyperinsulinemic euglycemic clamps revealed that the HFMCT and HFLCT resulted in severe whole body insulin resistance (glucose infusion rate: 53.1±6.8, 50.8±15.3 vs. 124.6±25.4 µmol min(-1) kg(-1), P<.001 in HFMCT, HFLCT and LF-fed mice, respectively). However, under hyperinsulinemic conditions, HFMCT revealed a lower endogenous glucose output (22.6±8.0 vs. 34.7±8.5 µmol min(-1) kg(-1), P<.05) and a lower peripheral glucose disappearance (75.7±7.8 vs. 93.4±12.4 µmol min(-1) kg(-1), P<.03) compared to HFLCT-fed mice. In conclusion, both HF diets induced whole body insulin resistance compared to LF. However, the HFMCT gained less weight, had less ectopic lipid accumulation, while peripheral insulin resistance was more pronounced compared to HFLCT. This suggests that HF-diets rich in medium- versus long-chain triacylglycerols induce insulin resistance via distinct mechanisms.
Subject(s)
Dietary Fats/administration & dosage , Fatty Acids/administration & dosage , Insulin Resistance/physiology , Animals , Dietary Fats/pharmacology , Energy Intake , Glucose/metabolism , Male , Mice , Mice, Inbred C57BL , Triglycerides/administration & dosageABSTRACT
The stable isotope dilution measurement of bile acid pool sizes and turnover rates in humans has involved the collection of nine blood samples over four days. This precludes widespread application to larger population studies. This study describes a two time-point approach for blood sampling without loss of statistical power. Isotopic decay curves of cholic acid, chenodeoxycholic acid and deoxycholic acid acquired in three recent human studies were analysed. The optimal combination of two time-points was determined. Time-points around 12 and 72 h after administration allowed for the most accurate description of the decay curves and prediction of kinetic parameters. Analyses of 39 statistical comparisons of kinetic parameters based upon the two time-points and all time-points approaches exhibited only one slightly discrepant result. In conclusion, for group comparison of bile acid kinetics in humans, a two time-point blood collection approach at time-points near 12 and 72 h provides statistically reliable data.
Subject(s)
Bile Acids and Salts/blood , Carbon Isotopes/analysis , Deuterium/analysis , Chenodeoxycholic Acid/blood , Cholic Acid/blood , Deoxycholic Acid/blood , Diabetes Mellitus, Type 2/blood , Female , Humans , Hypertriglyceridemia/blood , Isotope Labeling/methods , Kinetics , Male , Obesity/blood , Radioisotope Dilution Technique , Reference Values , Time FactorsABSTRACT
Flavonoids have inhibiting effects on the proliferation of cancer cells, including thyroidal ones. In the treatment of thyroid cancer the uptake of iodide is essential. Flavonoids are known to interfere with iodide organification in vitro, and to cause goiter. The influence of flavonoids on iodine metabolism was studied in a human thyroid cancer cell line (FTC-133) transfected with the human sodium/iodide transporter (NIS). All flavonoids inhibited growth, and iodide uptake was decreased in most cells. NIS mRNA expression was affected during the early hours after treatment, indicating that these flavonoids can act on NIS. Pendrin mRNA expression did not change after treatment. Only myricetin increased iodide uptake. Apeginin, luteolin, kaempferol and F21388 increased the efflux of iodide, leading to a decreased retention of iodide. Instead myricetin increased the retention of iodide; this could be of use in the radioiodide treatment of thyroid cancer.
