07/04/17

Tuesday, July 4, 2017

WHO Director-General Dr Tedros will lead WHO delegation at the G20 Summit in Hamburg

Dr Tedros Adhanom Ghebreyesus, WHO Director-General, will lead the WHO delegation participating in the G20 Summit taking place on 7–8 July 2017, in Hamburg, Germany. The 2017 G20 meeting is the first time that the international forum will include a comprehensive health track among its deliberations.

From: http://www.who.int/entity/mediacentre/news/releases/2017/G20-Summit/en/index.html

Gastric and Postgastric Processing of 13C Markers Renders the 13C Breath Test an Inappropriate Measurement Method for the Gastric Emptying of Lipid Emulsions in Healthy Adults [Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions]

Background: Breath tests (BTs) present an alternative gastric-emptying (GE) measure. However, their efficacy in the measurement of the GE rate of lipid emulsions (LEs) is unknown.

Objective: The objective of this work was to investigate the validity of ¹³C BTs as a measure of fat GE rate in LEs.

Methods: The lipophilic ¹³C octanoate (OCC) BT marker was investigated for fat GE with the hydrophilic ¹³C sodium acetate (ACC) and the triglyceride ¹³C trioctanoin (TCC) markers as comparators. Data from 2 randomized studies were combined [50 healthy participants; 25 men, mean ± SD age: 23 ± 2.8 y; mean ± SD body mass index (in kg/m²): 22.4 ± 1.7]. Each participant was given either an acid-stable LE (LE1) or an acid-unstable LE (LE4) at each visit. Twenty-three participants underwent simultaneous MRI. The effect of LEs on ¹³CO₂ excretion profiles was determined. The BT half-emptying times (BT T₅₀) were validated with the MRI half-emptying time of the ingested fat volume (MRI T₅₀).

Results: The effect of LEs on ¹³CO₂ excretion depended on the properties of the ¹³C marker. T₅₀ for OCC was shorter by 98 min for LE1 than for LE4 (P < 0.001). Other markers showed either no LE dependency or a longer T₅₀ for LE1 than for LE4. No difference in T₅₀ between OCC and ACC was detected in LE1. In LE4, the T₅₀ was longer by 154 min (P < 0.0001). There was some concordance between MRI T₅₀ and OCC BT T₅₀ for LE1 (r_c = 0.7). No other marker showed any concordance with fat GE. ¹³C-Nuclear magnetic resonance in vitro findings were compatible with changes in the kinetics of phase transfer of OCC dependent on its protonation state.

Conclusions: The structure of fat present in the stomach affects ¹³CO₂ excretion. The chemical properties of the ¹³C marker and their gastric and postgastric interaction with fat renders ¹³CO₂ excretion an inappropriate measure of LE emptying in healthy adults. This trial was registered at clinicaltrials.gov as NCT02226029 and NCT02602158.

From: Parker, H. L., Liu, D., Curcic, J., Ebert, M.-O., Schwizer, W., Fried, M., Steingoetter, A. http://jn.nutrition.org/cgi/content/short/147/7/1258?rss=1

Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or Obese Adults with Elevated Triglycerides [Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions]

Background: Hypertriglyceridemia is a common condition in the United States and is often associated with other metabolic disturbances, including insulin resistance, metabolic syndrome, and a predominance of small dense LDL particles.

Objective: The objective of this trial was to evaluate the effects of a combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted for refined starches and added sugars on insulin sensitivity (primary outcome) and other cardiometabolic health markers in overweight or obese adults with elevated triglyceride (TG) concentrations.

Methods: Subjects with elevated TG concentrations were given test foods prepared by using Epro powder (~8% of energy) and vegetable oil (~8% of energy; Epro and UFA condition) or test foods prepared by using refined starch and sugar (~16% of energy; carbohydrate condition) in a randomized, double-blind, controlled-feeding, crossover trial (3 wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI), fasting lipids, and other cardiometabolic health markers were assessed at baseline and the end of each diet condition. Responses were compared by using repeated-measures ANCOVA.

Results: Twenty-five participants [11 men, 14 women; mean ± SEM: age, 46.3 ± 2.4 y; body mass index (in kg/m²), 31.8 ± 1.0] with a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL (159, 228 mg/dL) completed the trial. The MISI value increased 18.1% ± 8.7% from baseline during the Epro and UFA condition and decreased 5.7% ± 6.2% from baseline during the carbohydrate condition (P < 0.001). The disposition index increased 23.8% ± 20.8% during the Epro and UFA condition compared with a decrease of 16.3% ± 18.8% during carbohydrate (P = 0.042) and LDL peak particle size increased 0.12 nm (–0.12, 0.28 nm) with Epro and UFA compared with a decrease of 0.15 nm (–0.33, 0.12 nm) with carbohydrate (P = 0.019). TG and VLDL cholesterol concentrations were lowered by 18.5% (–35.7%, –6.9%) and 18.6% (–34.8%, –7.4%), respectively, after the Epro and UFA condition and by 2.5% (–13.4%, 17.0%) and 3.6% (–12.5%, 16.2%), respectively, after the carbohydrate diet condition (P < 0.002).

Conclusions: The replacement of refined carbohydrates with a combination of Epro and UFA increased the MISI value and altered several markers of cardiometabolic health in overweight or obese adults with elevated TG concentrations. This trial was registered at clinicaltrials.gov as NCT02924558.

From: Maki, K. C., Palacios, O. M., Lindner, E., Nieman, K. M., Bell, M., Sorce, J. http://jn.nutrition.org/cgi/content/short/147/7/1267?rss=1

Intragastric Lysine Lowers the Circulating Glucose and Insulin Responses to a Mixed-Nutrient Drink without Slowing Gastric Emptying in Healthy Adults [Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions]

WHO: Rapidly ending an Ebola outbreak

From: World Health Organization https://www.youtube.com/watch?v=tNZi8MLsMWM

Pregnancy and bile acid disorders

During pregnancy, extensive adaptations in maternal metabolic and immunological physiology occur. Consequently, preexisting disease may be exacerbated or attenuated, and new disease susceptibility may be unmasked. Cholestatic diseases, characterized by a supraphysiological raise in bile acid levels, require careful monitoring during pregnancy. This review describes the latest advances in the knowledge of intrahepatic cholestasis of pregnancy (ICP), the most common bile acid disorder specific to pregnancy, with a focus on the disease etiology and potential mechanisms of ICP-associated adverse pregnancy outcomes, including fetal demise. The course of preexisting cholestatic conditions in pregnancy is considered, including primary sclerosing cholangitis, primary biliary cholangitis, biliary atresia, and Alagille syndrome. The currently accepted treatments for cholestasis in pregnancy and promising new therapeutics for the condition are described.

From: Pataia, V., Dixon, P. H., Williamson, C. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G1?rss=1

From sensing to shaping microbiota: insights into the role of NOD2 in intestinal homeostasis and progression of Crohns disease

NOD2 was the first susceptibility gene identified for Crohn’s disease (CD), one of the major forms of inflammatory bowel disease (IBD). The field of NOD2 research has opened up many questions critical to understanding the complexities of microbiota-host interactions. In addition to sensing its specific bacterial components as a cytosolic pattern recognition receptor, NOD2 also appears to shape the colonization of intestinal microbiota. Activated NOD2 triggers downstream signaling cascades exampled by the NF-B pathway to induce antimicrobial activities, however, defective or loss of NOD2 functions incur a similarly activated inflammatory response. Additional studies have identified the involvement of NOD2 in protection against non-microbiota-related intestinal damages as well as extraintestinal infections. We survey recent molecular and genetic studies of NOD2-mediated bacterial sensing and immunological modulation, and integrate evidence to suggest a highly reciprocal but still poorly understood cross talk between enteric microbiota and host cells.

From: Balasubramanian, I., Gao, N. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G7?rss=1

A new role for microbiota? Dulling the thrust of serotonin and 5-HT3 signaling cascade

From: Chang, E. B., Rao, M. C. http://ajpgi.physiology.org/cgi/content/full/313/1/G14?rss=1

Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine

Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with a broad array of physiological functions in many organs including the intestine. Its actions are mediated via G protein-coupled receptors, and vasoactive intestinal peptide receptor 1 (VPAC1) is the key receptor responsible for majority of VIP’s biological activity. The distribution of VPAC1 along the length of the gastrointestinal tract and its subcellular localization in intestinal epithelial cells have not been fully characterized. The current studies were undertaken to determine VPAC1 distribution and localization so that VIP-based therapies can be targeted to specific regions of the intestine. The results indicated that the mRNA levels of VPAC1 showed an abundance pattern of colon > ileum > jejunum in the mouse intestine. In parallel, the VPAC1 protein levels were higher in the mouse colon, followed by the ileum and jejunum. Immunofluorescence studies in mouse colon demonstrated that the receptor was specifically localized to the luminal surface, as was evident by colocalization with the apical marker villin but not with the basolateral marker Na⁺/K⁺-ATPase. In the human intestine, VPAC1 mRNA expression exhibited a distribution similar to that in mouse intestine and was highest in the sigmoid colon. Furthermore, in the human colon, VPAC1 also showed predominantly apical localization. The physiological relevance of the expression and apical localization of VPAC1 remains elusive. We speculate that apical VPAC1 in intestinal epithelial cells may have relevance in recognizing secreted peptides in the intestinal lumen and therefore supports the feasibility of potential therapeutic and targeting use of VIP formulations via oral route to treat gastrointestinal diseases.

NEW & NOTEWORTHY These studies for the first time present comprehensive data on the relative characterization of vasoactive intestinal peptide (VIP) receptors in the intestinal mucosa. Vasoactive intestinal peptide receptor 1 (VPAC1) was identified as the predominant receptor with higher levels in the colon compared with the small intestine and was mainly localized to the apical membrane. In addition, the findings in the human tissues were consistent with VPAC1 expression in the mouse intestine and open possibilities to target colonic tissues with VIP for treating diseases such as inflammatory bowel disease.

From: Jayawardena, D., Guzman, G., Gill, R. K., Alrefai, W. A., Onyuksel, H., Dudeja, P. K. http://ajpgi.physiology.org/cgi/content/abstract/313/1/G16?rss=1

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