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.

Twenty-four hour urinary cortisol excretion and the metabolic syndrome in prednisolone-treated renal transplant recipients.

Chronic prednisolone treatment in renal transplant recipients (RTR) causes metabolic abnormalities, which cluster in the metabolic syndrome (MS). It also suppresses the hypothalamic-pituitaryadrenal (HPA)-axis. We investigated whether HPA-axis suppression, as measured by 24h urinary cortisol excretion, is associated with presence of the MS and its individual components, in outpatient RTR with a functioning graft for >1year. Urinary cortisol was measured in 24h urine, using LC-MS/MS (LOQ 0.30nmol/L). We included 563 RTR (age 51±12years; 54% male) at median 6.0 [IQR, 2.6-11.5] years post-transplantation. MS was present in 439/563 RTR (78%). Median 24h urinary cortisol excretion was 2.0 [IQR, 0.9-5.1]nmol/24h. Twenty-four hour urinary cortisol excretion was independently associated with MS presence (OR=0.80 [95% CI, 0.66-0.98], P=0.02). It was also independently associated with bodyweight (st.ß=-0.11, P=0.007), waist circumference (st.ß=-0.10, P=0.01), BMI (st.ß=-0.14, P=0.001), fasting triglycerides (st.ß=-0.15, P=0.001), diabetes (st.ß=-0.12, P=0.005), and number of antihypertensives used (st.ß=-0.13, P=0.003). Suppressed HPA-axis activity, as reflected by decreased 24h urinary cortisol excretion, is associated with higher prevalence of MS and its individual components (i.e. central obesity, dyslipidemia, diabetes, hypertension) in prednisolone-treated RTR. Assessment of 24h urinary cortisol excretion by LC-MS/MS may be a tool to monitor metabolic side-effects of prednisolone in RTR.

Hypomagnesemia and atherogenic dyslipidemia in chronic kidney disease: surrogate markers for increased cardiovascular risk.

BACKGROUND: Recent reports suggest that 40-70 % chronic kidney disease (CKD) patients receiving dialysis have significant coronary artery disease. Magnesium depletion is being considered as the missing link between the cardiovascular risk factors and atherosclerosis in CKD. The present work aimed to study the association between magnesium status and lipid alterations in pre-dialysis CKD patients attending the Nephrology Clinic in a tertiary care hospital in South India. METHODS: 90 cases of CKD and 90 age and gender matched healthy controls were included in the study. Framingham risk scoring was done and presence of metabolic syndrome was assessed. Lipid profile, serum and urine magnesium, blood glucose, calcium, phosphorus, urea and creatinine levels were assayed in all study subjects. RESULTS: In this study we observed a significantly lower serum magnesium levels and dyslipidemic alterations, a significantly raised total cholesterol and low-density lipoprotein and non-HDL in patients with CKD. We also observed a significant correlation between the lowered serum magnesium concentrations and atherogenic dyslipidemia, suggesting a link to increased cardiovascular risk in CKD patients. CKD patients had higher risk of cardiovascular disease (according to their Framingham risk score), which also showed significant correlation with the hypomagnesaemia. CONCLUSIONS: Our results suggest a strong association of hypomagnesemia and atherogenic dyslipidemia in patients with CKD. This gains particular importance in the high cardiovascular risk-borne CKD patients, as supplementing magnesium would go a long way in reducing the risk of cardiovascular morbidity and mortality in CKD.

Urinary enterolactone is associated with obesity and metabolic alteration in men in the US National Health and Nutrition Examination Survey 2001-10.

Phyto-oestrogens are a family of plant-derived xeno-oestrogens that have been shown to prevent cancer in some studies. Whether phyto-oestrogen intake affects obesity status in a population is still unclear. In the present cross-sectional study, we examined the association of urinary phyto-oestrogen metabolites with obesity and metabolic parameters in children and adults. Data from 1294 children (age 6-19 years) and from 3661 adults (age ≥ 20 years) who participated in the US National Health and Nutrition Examination Survey 2001-10 were analysed. Multivariate logistic regression was applied to investigate the associations of BMI, waist circumference, serum metabolites (total cholesterol, HDL-cholesterol, LDL-cholesterol, TAG, fasting glucose and fasting insulin) and the metabolic syndrome with urinary phyto-oestrogen levels. When stratified by age and sex, we found a stronger association (OR 0·30, 95 % CI 0·17, 0·54; P< 0·001) between urinary enterolactone levels and obesity in adult males (age 20-60 years) than in children (age 12-19 years) or the elderly (age >60 years) in the same survey. However, no associations with urinary daidzein, O-desmethylangolensin, equol, enterodiol or genistein were found in the overall population. We also found that the elevation of enterolactone levels was inversely associated with TAG levels, fasting glucose levels, fasting insulin levels and the metabolic syndrome in males aged 20-60 years, but positively associated with HDL-cholesterol levels. The present results provide epidemiological evidence that urinary enterolactone is inversely associated with obesity in adult males.

Cardiometabolic risk factors are associated with high urinary enterolactone concentration, independent of urinary enterodiol concentration and dietary fiber intake in adults.

The study objective was to evaluate independent and interactive associations of dietary fiber intake and high urinary enterolignans with cardiometabolic risk factors. The analysis included 2260 adults (≥20 y of age) from the 2003-2010 NHANES. Logistic regression models were used to evaluate obesity and clinically defined cardiometabolic risk factors in relation to dietary fiber intake and urinary enterolignan concentrations. Three sets of models were created: 1) independent associations, 2) mutually adjusted associations, and 3) interactions. Models were adjusted for age, gender, race/ethnicity, education, smoking status, and energy intake. High concentrations were considered to be above the 90th percentile of urinary enterolignan concentrations. Increasing dietary fiber intake was associated with high blood pressure (P = 0.02) and low serum HDL cholesterol (P-trend = 0.03). High urinary enterodiol concentration was not associated with obesity or cardiometabolic risk factors. High urinary enterolactone concentration was inversely associated with obesity (OR: 0.44; 95% CI: 0.29, 0.66), abdominal obesity (OR: 0.58; 95% CI: 0.39, 0.87), high serum C-reactive protein (CRP; OR: 0.52; 95% CI: 0.37, 0.74), high serum triglycerides (OR: 0.39; 95% CI: 0.23, 0.61), low serum HDL cholesterol (OR: 0.37; 95% CI: 0.23, 0.61), and metabolic syndrome (OR: 0.47; 95% CI: 0.30, 0.74). In mutually adjusted models, enterolactone associations observed in independent models remained similar, but associations for dietary fiber intake were attenuated, with the exception of blood pressure. In interaction models, there were 2 significant interactions: between high urinary enterodiol concentration and dietary fiber intake for high serum CRP (P = 0.04) and high plasma glucose (P = 0.04). Overall, being in the highest 10% of urinary enterolactone concentration was associated with cardiometabolic risk factors, independent of dietary fiber intake and enterodiol concentration. Future studies are warranted to evaluate physiologic actions of enterolactone or aspects of the gut microbial profile responsible for lignan metabolism to enterolactone.

The association between urinary phytoestrogen excretion and components of the metabolic syndrome in NHANES.

BACKGROUND: Metabolic syndrome is a major risk factor for cardiovascular diseases, which are still the major cause of death in developed countries. METHODS: We cross-sectionally studied the association between urinary phytoestrogen excretion and metabolic cardiovascular risk factors. Hence, we used data from the National Health and Nutrition Examination Survey from 1999 to 2004 with 1,748 participants, who had urine levels of isoflavones and lignans measured. Geometric means of waist circumference, blood pressure, fasting glucose, HDL cholesterol, and triglyceride levels were computed by quartiles of isoflavone or lignan urinary excretion. Outcome was assessed as the presence of metabolic syndrome according to NCEP-ATP III criteria. The association between phytoestrogen concentration and the metabolic syndrome was calculated using logistic regression analyses. RESULTS: Plasma triglyceride and HDL cholesterol levels were lower in participants in the highest quartile of lignan excretion compared with the lowest (both P < 0.01). However, blood pressure, waist circumference, and plasma glucose levels did not differ significantly between extreme quartiles. The presence of metabolic syndrome was lower with increasing levels of urinary lignans (OR 0.48, 95% CI 0.28; 0.80 top vs. bottom quartile), especially when separately computed for the excretion of enterolactone (OR 0.47, 95% CI 0.28; 0.78). There was no significant association between isoflavone excretion and any component of the metabolic syndrome. CONCLUSIONS: Our study shows that an increasing excretion of lignans, especially enterolactone, might be associated with a decreased presence of the metabolic syndrome.