High-fat simple carbohydrate (HFSC) diet impairs hypothalamic and corpus striatal serotonergic metabolic pathway in metabolic syndrome (MetS) induced C57BL/6J mice.

OBJECTIVES: To study the effect of specially formulated high-fat simple carbohydrate diet (HFSC) on the serotonin metabolic pathway in male C57BL/6J mice. METHODS: Previous studies from our laboratory have shown that specially formulated HFSC induces metabolic syndrome in C57BL/6J mice. In the present investigation, 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid were analyzed in two brain regions (hypothalamus, corpus striatum), urine and plasma of HFSC-fed mice on a monthly basis up to 5 months using high-performance liquid chromatography fitted with electrochemical detector. The data were analyzed using Graph pad Prism v7.3 by two-way ANOVA and post hoc Tukey's test (to assess the effect of time on the serotonergic metabolic pathway). RESULTS: HFSC feed was observed to lower the hypothalamic serotonergic tone as compared to the age-matched control-fed C57BL/6J mice. Although the hypothalamic serotonergic tone was unaltered over time due to consumption of diet per se, hypothalamic 5-HTP levels were observed to be lower on consumption of HFSC feed over duration of 5 months as compared to 1st month of consumption of HFSC feed. The striatal 5-HTP levels were lowered in the HFSC-fed mice after 4 months of feeding as compared to the age-matched control-fed mice. The striatal 5-HTP levels were also lower in both control and HFSC-fed mice due to consumption of the respective diet over a duration of 5 months. Increased plasma 5-HTP levels were observed due to consumption of HFSC feed over duration of 5 months in the HFSC-fed group. However, higher breakdown of serotonin was observed in both the plasma and urine of HFSC-fed C57BL/6J mice as per the turnover studies. DISCUSSION: The central and peripheral serotonergic pathway is affected differentially by both the type of diet consumed and the duration for which the diet is consumed. The hypothalamic, striatal and plasma serotonergic pathway were altered both by the type of feed consumed and the duration of feeding. The urine serotonergic pathway was affected by mainly the duration for which a particular diet was consumed. These findings may have implications in the feeding behavior, cognitive decline and depression associated with metabolic syndrome patients.

The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants.

BACKGROUND: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS: Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ≥20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS: The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS: Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION: The trial was registered in India (CTRI/2012/05/002677).

High-fat simple carbohydrate feeding impairs central and peripheral monoamine metabolic pathway triggering the onset of metabolic syndrome in C57Bl/6J mice.

BACKGROUND: Previous studies have shown disturbances in an individual monoamine pathway but have not studied metabolic pathways at the onset and progression of metabolic syndrome (MetS). Aims, Settings, and Design: The aim of this study was to investigate the effect of high-fat simple carbohydrate (HFSC) diet on central (hypothalamic) and peripheral (plasma and urine) monoamine metabolic pathways during the development of metabolic syndrome in C57BL/6J mice. MATERIALS AND METHODS: Monoamines were analyzed in the 1st, 2nd, 3rd, 4th, and 5th month after feeding mice the HFSC diet or the control diet using the high performance liquid chromatography (HPLC) system (Shimadzu, Japan). Data was statistically analyzed (by Student's t-test) using Graph Pad Instat Version 3.1. Post statistical analysis, Bonferroni correction was applied to the results of 2nd, 3rd, 4th, and 5th month in order to calculate the correct error in the study. RESULTS: Significantly lower hypothalamic, plasma, and urine dopamine, and higher hypothalamic and plasma levels of norepinephrine and normetanephrine levels were observed in the HFSC diet fed C57BL/6J mice as compared to the control diet fed C57BL/6J mice after 5 months of feeding. No consistent changes were observed in other brain regions. The turnover ratio indicated that the lower dopamine levels in the HFSC diet fed C57BL/6J mice was due to the increased formation of norepinephrine and homovanillic acid. CONCLUSION: HFSC diet impairs the central and peripheral dopaminergic and noradrenergic pathways in mice as evidenced by the disturbances in their hypothalamic, plasma, and urine levels and this might be one of the early factors contributing towards the development of the MetS.