Aims/hypothesis Increased inflammation and oxidative stress are associated with insulin resistance (IR) and metabolic disorders. Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women. The objective of this study was to evaluate the efficacy of histidine supplementation on IR, inflammation, oxidative stress and metabolic disorders in obese women with the metabolic syndrome (MetS). Methods A total of 100 obese women aged 33-51 years with BMI≥28 kg/m 2 and diagnosed with MetS were included following a health examination in the community hospital in this randomised, double-blinded, placebo-controlled trial. Participants were allocated to interventions by an investigator using sequentially numbered sealed envelopes and received 4 g/day histidine (n=50) or identical placebo (n=50) for 12 weeks. Participants then attended the same clinic every 2 weeks for scheduled interviews and to count tablets returned. Serum histidine, HOMA-IR, BMI, waist circumference, fat mass, serum NEFA, and variables connected to inflammation and oxidative stress were measured at baseline and 12 weeks. Participants, examining physicians and investigators assessing the outcomes were blinded to group assignment. In addition, the inflammatory mechanisms of histidine were also explored in adipocytes. CI 0.60, 3.44] in histidine supplementation group (n=45), respectively. There were significant correlations between changes in serum histidine and changes of IR and its risk factors. No side effects were observed during the intervention. In vitro study indicated that histidine suppresses IL6 and TNF mRNA expression and nuclear factor kappa-B (NF-κB) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-κB. Conclusions/interpretation Histidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress inflammation and oxidative stress in obese women with MetS; histidine could improve IR through suppressed pro-inflammatory cytokine expression, possibly by the NF-κB pathway, in adipocytes. Trial registration www.chictr.org/cn/ChiCTR-TRC-11001551Electronic supplementary material The online version of this article

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Background: Obese individuals are more likely to have either lower blood concentrations or lower bioavailability of minerals and/or vitamins. However, there are limited data on the effects of nutritional supplementation on body weight (BW) control, energy homeostasis and lipid metabolism in obese subjects. Objective: The purpose of this study is to evaluate the effects of supplementation with multivitamin and multimineral on adiposity, energy expenditure and lipid profiles in obese Chinese women. Design: A total of 96 obese Chinese women (body mass index (BMI) 28 kg m À2 ) aged 18-55 years participated in a 26-week randomized, double-blind, placebo-controlled intervention study. Subjects were randomized into three groups, receiving either one tablet of multivitamin and mineral supplement (MMS), or calcium 162 mg (Calcium) or identical placebo daily during the study period. BW, BMI, waist circumference (WC), fat mass (FM), fat-free mass, resting energy expenditure (REE), respiratory quotient (RQ), blood pressure, fasting plasma glucose and serum insulin, total cholesterol (TC), low-and high-density lipoprotein-cholesterol (LDL-C and HDL-C) and triglycerides (TGs) were measured at baseline and 26 weeks. Results: A total of 87 subjects completed the study. After 26 weeks, compared with the placebo group, the MMS group had significantly lower BW, BMI, FM, TC and LDL-C, significantly higher REE and HDL-C, as well as a borderline significant trend of lower RQ (P ¼ 0.053) and WC (P ¼ 0.071). The calcium group also had significantly higher HDL-C and lower LDL-C levels compared with the placebo group. Conclusion: The results suggest that, in obese individuals, multivitamin and mineral supplementation could reduce BW and fatness and improve serum lipid profiles, possibly through increased energy expenditure and fat oxidation. Supplementation of calcium alone (162 mg per day) only improved lipid profiles.

Recent studies have shown that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme for the pentose phosphate pathway, was involved in insulin resistance via reduced nicotinamide adenine dinucleotide phosphate, while the roles of pentose were not examined. In the present study, the association of G6PD, pentose, and pentosidine with insulin resistance was investigated in diet-induced obesity of rats. Male Wistar rats were fed a high-fat diet for 6 weeks to generate obesity-prone (OP, n=14) and obesity-resistant (OR, n=14) rats. The levels of G6PD, pentose, and pentosidine, and oxidative stress were analyzed in serum and tissues. The OP rats, compared to the OR and control rats, had a significant increase in body weight (16.2% and 12.8%), serum triglyceride (43.4% and 12.3), and free fatty acids (49.5% and 23.6%), and developed marked insulin resistance. G6PD activities were increased in the pancreas and liver with upregulated pentose levels in serum, pancreas, and liver of OP rats. Pentosidine levels were increased only under the condition of high pentose levels and oxidative stress status in serum and pancreas of OP rats. G6PD activities in pancreas and liver, pentose levels in serum, pancreas, and liver, and pentosidine levels in serum and pancreas were positively correlated with homeostasis model of assessment-insulin resistance. Our results suggest that the upregulation of G6PD causes an increase in the accumulation of pentose and pentosidine, which might be associated with insulin resistance in the condition of obesity.

BackgroundAlthough several new drugs have been approved in recent years, pulmonary arterial hypertension (PAH) remains a rapidly progressive disease with a poor prognosis. Ambrisentan, a selective endothelin type A antagonist, has been approved for treatment of PAH. This open label study assessed the efficacy and safety of ambrisentan in Chinese subjects with PAH.MethodsEligible patients with PAH (World Health Organisation [WHO] functional class [FC] II orIII) were enrolled and received Ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period (dose titration to 10 mgallowed). Endpoints included: change from baseline in 6-Minute Walk Distance (6-MWD), N-Terminal Pro B-Type Natriuretic Peptide (NT-pro-BNP), WHO FC, Borg Dyspnoea Index (BDI), clinical worsening of PAH and incidences of adverse events (AE).ResultsOne hundred thirty-three subjects (85 % women, mean age: 36 years) with PAH (WHOFC II or III) were enrolled and received ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period. Mean (SD) duration of drug exposure was 161.7 (27.13) days. Ambrisentan (average daily dose of 6.27 mg) significantly improved exercise capacity (6MWD) from baseline (mean: 377.1 m [m]) at week 12 (+53.6 m, p < 0.001) (primary endpoint). Improvement in exercise capacity was noted as early as week 4, and was sustained up to week 24 (+ 64.4 m, p < 0.001). NT-pro-BNP plasma levels decreased significantly (p < 0.001) at week 12 (−861.4 ng/L) and week 24 (−806 ng/L) from baseline (mean: 1600.7 ng/L). The WHO FC showed improvements for 44 subjects at week 12 and 51 subjects at week 24. BDI scores decreased significantly at week 12 (−0.3, p < 0.001) and week 24 (−0.2, p = 0.003) from baseline (mean: 2.5). Four patients died during the study (sudden cardiac death [n = 2], cerebral haemorrhage [n = 1], cardiac failure [n = 1]). Drug related adverse events occurred in 34.3 % of subjects; peripheral oedema (11.2 %) and flushing (8.2 %) occurred most frequently.ConclusionAmbrisentan (5 and 10 mg, orally) significantly improved the exercise capacity in Chinese PAH subjects with a safety profile similar to that observed in global studies.Trial registrationNCT No. (ClinicalTrials.gov): NCT01808313; Registration date (first time): February 28, 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0361-9) contains supplementary material, which is available to authorized users.