Postprandial Acid Research Articles

The Role of Baclofen in the Treatment of Gastroesophageal Reflux Disease.

Objective. To describe the evidence for baclofen in the treatment of gastroesophageal reflux disease (GERD). Data Sources. A search of PubMed and Google Scholar was performed using the terms baclofen, gastroesophageal reflux disease, and treatment. Study Selection and Data Extraction. Publications were reviewed manually for relevance, and studies that addressed the use of baclofen in the treatment of adult symptomatic GERD patients were included. Data Synthesis. Nine studies were evaluated. Baclofen was shown to significantly reduce transient lower esophageal sphincter relaxations (TLESRs), postprandial acid reflux events, and median number of acid-related symptoms in 6 studies evaluating either a single dose of baclofen or short courses of 2 days or less. Three studies followed patients over a slightly longer period of time. These studies confirmed the results of the shorter trials by finding a decrease in supine duodenal reflux episodes, decreased periods when the pH was less than 4, and improvements in symptom scores in patients refractory to proton pump inhibitors. Side effects most frequently reported included drowsiness and dizziness. Conclusions. Baclofen can be considered for the treatment of refractory GERD following diagnostic evaluation. It has been shown to reduce TLESRs, reflux episodes, and reflux-related symptoms with minimal side effects in short-term trials. Future studies demonstrating the long-term efficacy and tolerability of baclofen in the treatment of GERD would help solidify its place in therapy.

Older Adults Have Delayed Amino Acid Absorption after a High Protein Mixed Breakfast Meal.

To measure the postprandial plasma amino acid appearance in younger and older adults following a high protein mixed meal. Cross-sectional study. Clinical research setting. Healthy men and women aged 60-75 (n=15) years, and young controls aged 20-25 years (n=15) matched for body mass index and insulin sensitivity based on the homeostatic model assessment of insulin resistance. High protein mixed meal of complete food products. Circulating amino acid concentrations were determined hourly before and for 5 hours after meal ingestion. There was no difference between cohorts in postprandial appearance of non-essential amino acids, or area under the curve of any individual amino acid or amino acid class. However, older adults had higher baseline concentrations of aspartic acid, glutamic acid, glycine, ornithine, threonine and tyrosine and lower baseline concentrations of hydroxyproline, isoleucine, leucine, methionine and valine compared to younger adults. Younger adults showed peak essential (EAA) and branched-chain amino acid (BCAA) concentrations at 1 hour post meal while older adults' peak EAA and BCAA concentration was at 3 hours. Similarly, peak total amino acid concentrations were at 3 hours in older adults. Older adults digested and absorbed the protein within a mixed meal more slowly than younger adults. Delayed absorption of AA following a mixed meal of complete food products may suppress or delay protein synthesis in senescent muscle.

Protein type and caloric density of protein supplements modulate postprandial amino acid profile through changes in gastrointestinal behaviour: A randomized trial

The requirement of leucine and essential amino acids (EAA) to stimulate muscle protein synthesis increases with age. To target muscle anabolism it is suggested that higher postprandial blood levels of leucine and EAA are needed in older people. The aim was to evaluate the impact of oral nutritional supplements with distinct protein source and energy density, resembling mixed meals, on serum amino acid profiles and on gastrointestinal behaviour. Four iso-nitrogenous protein (21 g) supplements were studied containing leucine-enriched whey protein with 150/320 kcal (W150/W320) or casein protein with 150/320 kcal (C150/C320); all products contained carbohydrates (10 or 32 g) and fat (3 or 12 g). Postprandial serum AA profiles were evaluated in twelve healthy, older subjects who participated in a randomized, controlled, single blind, cross-over study. Gastrointestinal behaviour was studied in vitro by looking at gastric coagulation and cumulative intestinal protein digestion over time. The peak serum leucine concentration was twofold higher for W150 vs. C150 (521 ± 15 vs. 260 ± 15 μmol/L, p < 0.001), higher for W320 vs. C320 (406 ± 15 vs. 228 ± 15 μmol/L, p < 0.001), and higher for low-caloric vs. high-caloric products (p < 0.001 for pooled analyses; p < 0.001 for interaction protein source*caloric density). Similar effects were observed for the peak concentrations of EAA and total AA (TAA). In vitro gastric coagulation was observed only for the casein protein supplements. Intestinal digestion for 90 min resulted in higher levels of free TAA, EAA, and leucine for W150 vs. C150, for W150 vs. W320, and for C150 vs. C320 (p < 0.0125). A low caloric leucine-enriched whey protein nutritional supplement provides a higher rise in serum levels of TAA, EAA and leucine compared to casein protein or high caloric products in healthy, elderly subjects. These differences appear to be mediated in part by the gastrointestinal behaviour of these products. ClinicalTrials.gov: NCT02013466.

Experimental dog model for assessment of fasting and postprandial fatty acid metabolism: pitfalls and feasibility.

The dog is a widely-used model for conducting metabolic studies. This is mainly due to its large size and its physiology which is relatively similar to that of humans. Here, we attempted to optimize a postprandial metabolic study protocol used in dogs. Following acclimatization, female mongrel dogs underwent 9 h profiling for time-course baseline plasma data on triglyceride, adrenocorticotropic hormone (ACTH) and cortisol levels. One week later, carotid and jugular catheters were surgically inserted for sampling and infusions. Initial post-operative care, based on the literature (Protocol 1), consisted of analgesia (buprenorphine every 8-12 h and 2-3 doses/day of acepromazine), restriction by Pavlov harness within cages, and a two- to three-day recovery period. Throughout the experiment, dogs received a lipid tracer diluted in 5% bovine serum albumin (BSA). Compared with baseline, animals vomited (n = 6/6) and exhibited high ACTH + cortisol levels (stress biomarkers), resulting in blunted triglyceride peak levels. To avoid these undesirable effects, post-operative care was modified (Protocol 2) as follows: animals (n = 19) were given a single dose of buprenorphine and no acepromazine, were unrestrained and free to move within cages, the recovery period was extended to seven days, and the lipid tracer was diluted in 0.002% versus 5% BSA. Using this modified protocol, postprandial plasma-triglyceride and ACTH/cortisol patterns were similar to baseline values. Controlling for stressors, as well as for factors which may alter proper digestion, is critical for all postprandial metabolic studies. Our results show that an optimized postprandial metabolic protocol used in dogs reduces experimental variability, while improving animal care and comfort.

Postprandial effects of polydextrose on satiety hormone responses and subjective feelings of appetite in obese participants.

BackgroundDietary fibers are associated with enhanced satiety. However, the mechanism of different dietary fibers contributing to satiety-related gastrointestinal (GI) peptide release, especially in an obese population, is still poorly understood. Polydextrose (PDX), a water-soluble glucose polymer, has demonstrated its ability to reduce energy intake at a subsequent meal, but its mechanism of action requires further research. Also, there is limited evidence on its capacity to regulate subjective feelings of appetite. This study examines the effects of PDX on postprandial secretion of satiety-related GI peptides, short chain fatty acids (SCFAs), lactic acid, and subjective appetite ratings in obese participants.Methods18 non-diabetic, obese participants (42.0 y, 33.6 kg/m2) consumed a high-fat meal (4293 kJ, 36% from fat) with or without PDX (15 g) in an acute, multicenter, randomized, double-blind, placebo-controlled and crossover trial. Postprandial plasma concentrations of satiety-related peptides, namely ghrelin, cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), as well as SCFAs and lactic acid were assessed. GI peptide, SCFA and lactate concentrations were then modeled using a linear mixed-effects model.The subjective feelings of hunger, satisfaction, and desire to eat were evaluated using visual analogue scales (VAS), which were analyzed as incremental areas under the curve (iAUC) during the satiation and satiety periods.ResultsWe found that PDX supplementation increased plasma GLP-1 levels more than the placebo treatment (P = 0.02). In the whole group, GLP-1 concentrations found in participants older than 40 years old were significantly lower (P = 0.01) as compared to those aged 40 years or less. There were no statistically significant differences in postprandial ghrelin, CCK, or PYY responses. The lactic acid concentrations were significantly (P = 0.01) decreased in the PDX group, while no significant changes in SCFAs were found. PDX reduced iAUC for hunger by 40% (P = 0.03) and marginally increased satisfaction by 22.5% (P = 0.08) during the post-meal satiety period.ConclusionPolydextrose increased the postprandial secretion of the satiety hormone GLP-1 and reduced hunger after a high-fat meal. PDX also reduced the elevated postprandial lactic acid levels in plasma. Therefore, PDX may offer an additional means to regulate inter-meal satiety and improve postprandial metabolism in obese participants.

Desaturation index versus isotopically measured de novo lipogenesis as an indicator of acute systemic lipogenesis.

BackgroundHigh carbohydrate feeding is known to increase plasma triglycerides as well as hepatic de novo lipogenesis (DNL) and may be implicated in the development of hepatic insulin resistance and fatty liver. Unfortunately, it is technically challenging to determine what proportion of circulating plasma triglycerides have been derived from the newly synthesized fatty acids in the postprandial period. The aims of this study were to 1) characterize the changes in the plasma postprandial total fatty acid pool in beagles following the consumption of meals containing 44% (Control) and 74% (High Sucrose) carbohydrate and 2) determine if changes in plasma fatty acid concentration and delta-9 desaturation index (DI) would be useful as simple and easy to measure biomarkers of systemic DNL.FindingsNo differences in plasma total palmitic acid (16:0), stearic acid (18:0) and oleic acid (18:1) concentrations or delta-9 DI for the total 18:0 and 18:1 pools between High Sucrose and Controls were observed. However, newly synthesized 16:0 (2.6 ± 0.2% vs. 8.8 ± 2.0%; p = 0.016), 18:0 (0.93 ± 0.2% vs. 4.1 ± 1.7%; p = 0.007) and 18:1 (0.29 ± 0.09% vs. 3.5 ± 1.2%; p = 0.017) were higher in High Sucrose versus Control animals, respectively. Also, the delta-9 DI for the newly synthesized 18:0 and 18:1 pools was higher at 2 and 6 hours postprandial, with a pattern of change which supports the increased stearoyl-CoA desaturase (SCD-1) activity following high carbohydrate feeding followed by a down regulation of this enzyme.ConclusionsOur data show that high sucrose meals increase the relative contribution of systemic DNL produced fatty acids to the total postprandial plasma fatty acid pool. These data also show that a different pattern of both fatty acid synthesis and disposal occurs depending on energy and macronutrient profile of the meal. These changes are in spite of no observable changes in the plasma concentrations or ratios of the total fatty acid pool opposed to the observed changes in the newly synthesized fatty acid pool.

Some issues of the diagnosis and treatment of gastroesophageal reflux disease

The clinical inefficacy of proton pump inhibitors (PPIs) is very frequently encountered in nonerosive gastroesophageal reflux disease (NERD) in particular. Postprandial acid pocket, weak-acid or alkaline reflux, etc. are one of the causes of resistance to antisecretory drugs. Alginates serve as a good alternative to PPIs in treating NERD and gastroesophageal reflux in children and pregnant women. The alginate test may help diagnose NERD.

Post-prandial amino acid and leucine responses to serum albumin concentrate compared to whey protein concentrate in healthy subjects

Background Supplemental protein sources vary in composition in regards to size, structure, and amino acid composition of the varying individual proteins. Serum albumin concentrate (SA) is a new protein source extracted from edible-grade bovine plasma, which was recently made available on commercial scale. As compared to the low MW proteins in whey protein concentrate (WPC), SA consists of higher MW protein constituents such as albumin (66kD, >60%) and globulin proteins (130 kD, >10%), which contain a high quality amino acid composition. These differences in the protein profile of SA may both delay and sustain amino acid absorption in comparison to WPC. The objective of this study was to determine the post-prandial amino acid response to oral ingestion of SA and to compare the response to that of WPC. Methods Eight healthy, 20-30 year old, male (n=4, 80.3 kg BW) and female (n=4, 63.7 kg BW) volunteers participated in an open label, clinical study utilizing a cross-over design (Clinicaltrials.gov: NCT01643265). The volunteers received each of the two protein sources in a random order with a 7 d washout period between treatments. After a 12 h overnight fast, 7 mL of blood was collected from a catheter inserted into a forearm vein. Baseline amino acid values at 30 and 15 min were determined prior to administration of the experimental protein sources. Twenty grams of either WPC or SA was provided in 335 mL of water. Subsequent blood samples were collected at 15, 30, 45, 60, 90, 120, 180, and 210 min after ingestion for analysis of individual amino acid concentrations. An EZ:faastTM amino acid analysis kit was used for sample pretreatment and chromatographic separation was conducted using a Agilent 6460 triple quadrupole LC/MS system. Data were analyzed using repeated measures and General Linear Models procedures from SAS (Version 9.2) including treatment, gender, and test period as independent variables in the statistical model. Significance is reported as P<0.05 and P<0.01. Consent to publish the results was obtained from all participants. Results Total plasma amino acid concentration at baseline was found to be higher (P<0.01) at baseline in male subjects (2,633 nmoles/mL) compared to female subjects (2,153 nmoles/mL). In contrast, plasma leucine concentration was found to be higher (P<0.05) in female subjects (156 nmoles/mL) compared to male subjects (103 nmoles/mL). Rises in post-prandial individual amino acid concentration were observed for both WPC and SA (P<0.01). The rises reflect the amino acid pattern of the protein source ingested. The ingestion of whey protein concentrate increased plasma total amino acid concentration 30 min post-prandially compared to SA (P<0.05) by 10%, without differences in leucine. In contrast, the ingestion of SA promoted 14% higher leucine concentrations 120 min post-prandially than did WPC (P<0.05). Conclusion Individual post-prandial amino acids reflect the amino acid pattern and characteristics of the protein source ingested. The digestion and absorption of the protein and amino acid composition of serum albumin concentrate

Effect of plant proteins and crystalline amino acid supplementation on postprandial plasma amino acid profiles and metabolic response in rainbow trout (Oncorhynchus mykiss)

The use of aquafeeds formulated with plant protein sources supplemented with crystalline amino acids (CAAs) is believed to influence amino acid (AA) uptake patterns and AA metabolic fate. Oxygen consumption and ammonia excretion rates were measured in rainbow trout (468.5 ± 86.5 g) force fed 0.75 % of their body mass with a diet based on either (1) fish meal (FM), (2) pea protein concentrate (PPC), or (3) pea protein concentrate supplemented with histidine, lysine, methionine and threonine (PPC+) to mimic FM AA profile. The specific dynamic action and nitrogen quotient (NQ) were calculated for 48 h of the postprandial period. In parallel, plasma AA concentrations were measured in blood samples withdrawn from the caudal vein before and then 2, 4, 6, 8, 12, 20, 32 and 48 h after feed administration. The unbalanced diet PPC had a significantly higher NQ compared to FM (0.29 ± 0.09 and 0.18 ± 0.04, respectively), and plasma profiles of essential AAs reflected the dietary deficiencies. Supplementation with CAA in diet PPC+ resulted in an intermediary NQ (0.21 ± 0.04) and significantly affected plasma AA profiles, presenting greater and faster rises followed by sharp decreases compared to FM. The strongest effect was observed for methionine, presenting threefold higher concentrations at peak time for PPC+ compared to FM (297.0 ± 77.0 and 131.8 ± 39.0 nmol ml−1, respectively). The differences in AA availability and metabolic profile in the pea diets compared to the FM diet were believed to be caused by an unbalanced dietary AA profile and CAA supplementation, rather than inclusion of plant protein concentrate.

OP026: Intensive Exercise Hampers the Postprandial Citrulline Bioavailability Following Casein Bolus Feeding

Rationale: Metabolic stress like surgery and intensive exercise have been reported to increase intestinal permeability. It is not known whether intensive exercise also influences gut metabolic functioning. The effects of intensive exercise on intestinal permeability, postprandial amino acid (AA) bioavailability and intestinal enterocyte metabolic mass were determined in the human intervention study Protege.

The gastric mucosa 25 years after proximal gastric vagotomy

Objective. Vagotomy causes inhibition of basal and post-prandial acid secretion in humans, but the knowledge about the trophic effect of the vagal nerves is limited. Vagotomy is known to induce hypergastrinemia and we aimed to study the long-term effects of proximal gastric vagotomy (PGV) on the oxyntic mucosa and the enterochromaffin-like (ECL) cell density in particular. Material and methods. Eleven patients operated with PGV because of duodenal ulcer and age- and sex-matched controls were examined 26 to 29 years postoperatively by gastroscopy with biopsies from the antrum and oxyntic mucosa. Neuroendocrine cell volume densities were calculated after immunohistochemical labeling of gastrin, the general neuroendocrine cell marker chromogranin A (CgA) and the ECL cell marker vesicular monoamine transporter 2 (VMAT2). Gastritis was graded and Helicobacter pylori (H. pylori) status was determined by polymerase chain reaction of gastric biopsies. Fasting serum gastrin and CgA were measured. Results. Serum gastrin was higher in the PGV group compared to controls (median 21.0 [interquartile range (IQR) = 22.0] pmol/L vs 13.0 [IQR = 4.0] pmol/L, p = 0.04). However, there was neither a significant difference in serum CgA or in CgA (neuroendocrine) nor VMAT2 (ECL cell) immunoreactive cell volume density in the oxyntic mucosa. There was significantly more inflammation and atrophy in H. pylori-positive patients, but PGV did not influence the grade of gastritis. Conclusion. Despite higher serum gastrin concentrations, patients operated with PGV did not have higher ECL cell mass or serum CgA. Vagotomy may prevent the development of ECL cell hyperplasia caused by a moderate hypergastrinemia.

Dietary Medium Chain Fatty Acid Supplementation Leads to Reduced VLDL Lipolysis and Uptake Rates in Comparison to Linoleic Acid Supplementation

Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51±7 years; BMI 28.5±0.8 kg/m2), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a wash-out period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates.

Gaviscon Double Action Liquid (antacid & alginate) is more effective than antacid in controlling post-prandial oesophageal acid exposure in GERD patients: a double-blind crossover study.

Recent studies have shown that Gaviscon Double Action Liquid (a combination alginate-antacid) administered post-prandially co-localises with the acid pocket, the 'reservoir' for post-prandial acid reflux. To compare the effectiveness of Gaviscon Double Action Liquid to an equivalent strength antacid without alginate in controlling post-prandial acid reflux in GERD patients. Fourteen GERD patients undertook two 3.5-h high-resolution manometry/pH-impedance studies during which they ate a standardised meal. In a double-blinded randomised crossover design they then took Gaviscon or CVS brand antacid, each with ~18mmol/L acid neutralising capacity. The primary outcome was distal oesophageal acid exposure; secondary outcomes were number of reflux events, proximal extent of reflux, nadir pH of the refluxate, mechanism of reflux and reflux symptoms scored with a validated instrument. Ten patients completed the study. Gaviscon studies had significantly less distal oesophageal acid exposure and greater nadir refluxate pH in the 30-150min post-prandial period than antacid studies. There were no differences in the number of reflux events (acid or weakly acidic) or the number of proximal reflux events (15-17cm above the LES) with either study medication. Gaviscon Double Action Liquid is more effective than an antacid without alginate in controlling post-prandial oesophageal acid exposure. However, the number and spatial distribution of reflux events within the oesophagus are similar. This suggests that Gaviscon main effectiveness relates to its co-localisation with and displacement/neutralisation of the post-prandial acid pocket, rather than preventing reflux.

Effect of baclofen on the acid pocket at the gastroesophageal junction.

Previous studies established that a pocket of highly acidic gastric juice is present postprandially at the gastroesophageal junction in man. The GABA-B agonist baclofen inhibits postprandial reflux events through its effects on the lower esophageal sphincter (LES). The aim of the current study was to investigate whether baclofen would affect the location and the extent of the postprandial acid pocket in healthy volunteers. Twelve healthy volunteers underwent acid pocket studies on two different occasions, at least 1 week apart. LES position was determined preprandially with pull-through manometry. Dual pH electrode and manometry probe stepwise pull-through (1 cm/minute, LES-10 to +5 cm) was performed at 30-minute intervals for 150 minutes, with administration of placebo or baclofen 40 mg after the first and ingestion of a liquid meal after the second pull-through. After placebo, a significant drop in intragastric gastric pH was present at the gastroesophageal junction after the meal, reflecting the acid pocket, and this was associated with a drop in LES pressure. Baclofen did not affect the presence of the acid pocket, but prevented the postprandial drop in LES pressure, and the extent of the acid pocket above the upper margin of the manometrically located LES was significantly decreased by baclofen (1.6 ± 0.7 vs. 0.3 ± 0.4 cm at 60 minutes, 2.2 ± 0.6 vs. 0.2 ± 0.6 at 90 minutes, and 1.5 ± 0.5 vs. 0.7 ± 0.7 cm at 120 minutes, all P < 0.05). Baclofen does not alter the intragastric acid pocket, but limits its extension into the distal esophagus, probably through an increase in postprandial LES pressure.

Effects of 3-nitrooxypropanol on methane emission, digestion, and energy and nitrogen balance of lactating dairy cows

The objective was to measure effects of 3-nitrooxypropanol (3NP) on methane production of lactating dairy cows and any associated changes in digestion and energy and N metabolism. Six Holstein-Friesian dairy cows in mid-lactation were fed twice daily a total mixed ration with maize silage as the primary forage source. Cows received 1 of 3 treatments using an experimental design based on two 3×3 Latin squares with 5-wk periods. Treatments were a control placebo or 500 or 2,500mg/d of 3NP delivered directly into the rumen, via the rumen fistula, in equal doses before each feeding. Measurements of methane production and energy and N balance were obtained during wk 5 of each period using respiration calorimeters and digestion trials. Measurements of rumen pH (48 h) and postprandial volatile fatty acid and ammonia concentrations were made at the end of wk 4. Daily methane production was reduced by 3NP, but the effects were not dose dependent (reductions of 6.6 and 9.8% for 500 and 2,500mg/d, respectively). Dosing 3NP had a transitory inhibitory effect on methane production, which may have been due to the product leaving the rumen in liquid outflow or through absorption or metabolism. Changes in rumen concentrations of volatile fatty acids indicated that the pattern of rumen fermentation was affected by both doses of the product, with a decrease in acetate:propionate ratio observed, but that acetate production was inhibited by the higher dose. Dry matter, organic matter, acid detergent fiber, N, and energy digestibility were reduced at the higher dose of the product. The decrease in digestible energy supply was not completely countered by the decrease in methane excretion such that metabolizable energy supply, metabolizable energy concentration of the diet, and net energy balance (milk plus tissue energy) were reduced by the highest dose of 3NP. Similarly, the decrease in N digestibility at the higher dose of the product was associated with a decrease in body N balance that was not observed for the lower dose. Milk yield and milk fat concentration and fatty acid composition were not affected but milk protein concentration was greater for the higher dose of 3NP. Twice-daily rumen dosing of 3NP reduced methane production by lactating dairy cows, but the dose of 2,500mg/d reduced rumen acetate concentration, diet digestibility, and energy supply. Further research is warranted to determine the optimal dose and delivery method of the product.

Improved Cardiopulmonary Functional Capacity Following a One-Year Lifestyle Intervention Regimen Does Not Explain Improved Postprandial Myocardial Dietary Fatty Acid Metabolism in Patients with Impaired Glucose Tolerance

s / Can J Diabetes 38 (2014) 151e153 153 exposed to HG in normoxia (P1⁄40.0204 for PDGF) and in hypoxia. We observed that HG inhibited PDGF-induced vSMC migration, an effect that was amplifiedwhen exposed to hypoxia. Intriguingly, we did not observed any change in insulinor PDGF-stimulated Akt or ERK activation in cells treated with HG and/or hypoxia. In conclusion, hyperglycemia affects vSMC proliferation and migration in hypoxic condition. However, more experiments are needed to determine the mechanisms involved in this phenomenon. Funding: This work was supported by the Canadian association of diabetes (CDA) operating grant (P.G.). P.G is a recipient of a Canada Research Chair in Diabetes and Vascular Complications and Canadian Diabetes Association Scholar Award. M.P. is the recipient of a scholarship from Diabete Quebec.

Hepatocyte-specificPtpn6deletion promotes hepatic lipid accretion, but reduces NAFLD in diet-induced obesity: Potential role of PPARγ

Hepatocyte-specific Shp1 knockout mice (Ptpn6(H-KO)) are protected from hepatic insulin resistance evoked by high-fat diet (HFD) feeding for 8 weeks. Unexpectedly, we report herein that Ptpn6(H-KO) mice fed an HFD for up to 16 weeks are still protected from insulin resistance, but are more prone to hepatic steatosis, as compared with their HFD-fed Ptpn6(f/f) counterparts. The livers from HFD-fed Ptpn6(H-KO) mice displayed 1) augmented lipogenesis, marked by increased expression of several hepatic genes involved in fatty acid biosynthesis, 2) elevated postprandial fatty acid uptake, and 3) significantly reduced lipid export with enhanced degradation of apolipoprotein B (ApoB). Despite more extensive hepatic steatosis, the inflammatory profile of the HFD-fed Ptpn6(H-KO) liver was similar (8 weeks) or even improved (16 weeks) as compared to their HFD-fed Ptpn6(f/f) littermates, along with reduced hepatocellular damage as revealed by serum levels of hepatic enzymes. Interestingly, comparative microarray analysis revealed a significant up-regulation of peroxisome proliferator-activated receptor gamma (PPARγ) gene expression, confirmed by quantitative polymerase chain reaction. Elevated PPARγ nuclear activity also was observed and found to be directly regulated by Shp1 in a cell-autonomous manner. These findings highlight a novel role for hepatocyte Shp1 in the regulation of PPARγ and hepatic lipid metabolism. Shp1 deficiency prevents the development of severe hepatic inflammation and hepatocellular damage in steatotic livers, presenting hepatocyte Shp1 as a potential novel mediator of nonalcoholic fatty liver diseases in obesity.

Lactobacillus gasseri SBT2055 reduces postprandial and fasting serum non-esterified fatty acid levels in Japanese hypertriacylglycerolemic subjects

BackgroundLactobacillus gasseri SBT2055 (LG2055) inhibits dietary fat absorption in rats and exerts preventive effects on abdominal adiposity in rats and humans. The present study aimed to evaluate the effects of LG2055 on postprandial serum lipid responses in Japanese subjects with hypertriacylglycerolemia after the intake of oral fat-loading test (OFLT) meals.MethodsWe conducted a single-blind, placebo-controlled, within-subject, repeated-measure intervention trial. Twenty subjects initially ingested the fermented milk (FM) without LG2055 for 4 weeks (control FM period), followed by a 4-week washout period, and then consumed FM containing LG2055 for 4 weeks (active FM period). The subjects were asked to consume FM at 200 g/day. At the end of each 4-week period, an 8-h OFLT was conducted. Blood samples were collected at fasting and every hour for 8 h after OFLT meal intake. Thereafter, postprandial serum non-esterified fatty acid (NEFA) and triacylglycerol (TAG) levels and fasting blood parameters were measured.ResultsThe OFLT showed that the postprandial serum NEFA levels from 120 to 480 min and the postprandial serum TAG level at 120 min in the active FM period were significantly (P < 0.05) lower than those in the control FM period. The fasting serum NEFA level in the active FM period significantly (P < 0.001) decreased at week 4 from the initial period compared with the control FM period.ConclusionsThe consumption of probiotic LG2055 reduced postprandial and fasting serum NEFA levels, suggesting its possible contribution to the reduction of the risk for obesity and type 2 diabetes mellitus.Trial registrationUMIN000011605

Comparison of metabolic abnormalities in patients with new-diagnostic polycystic ovary syndrome and with new-diagnostic Type 2 diabetes mellitus

Background: Metabolic abnormalities have been widely studied in women with polycystic ovary syndrome (PCOS) and in patients with Type 2 diabetes mellitus (T2DM). However, there are few studies on the comparison of the metabolic disturbances between the two diseases although they have partly common pathogenesis. This study compares the metabolic parameters of PCOS and T2DM, and evaluates the association between metabolic parameters and gonadotropic hormones. Methods: Fifity newly diagnosed PCOS women and 56 newly diagnosed Type 2 diabetes women were enrolled in the study. The metabolic parameters including body mass index, waist to hip ratio, blood pressure, total cholesterol, triglycerides, high-density and low-density lipoprotein cholesterol, fasting and postprandial plasma glucose, fasting and postprandial plasma insulin, HOMA-IR index and uric acid, along with the gonadal and gonadotropic hormones were analyzed between the two groups. The lutein hormone (LH) responses to the GnRH stimulating test were compared between different glucose tolerance groups in PCOS women. The peak values of LH in the GnRH test are studied with metabolic parameters using Pearson correlation analysis. Results: PCOS patients have higher body weight index, waist to hip ratio, fasting and postprandial insulin, HOMA-IR and uric acid than T2DM patients. There are no significant differences in lipid metabolism excluding the age influence. On the other hand, T2DM patients have significantly higher systolic blood pressure and plasma glucose than those in PCOS patients. But there is less clinical significance in the level of plasma glucose. After GnRH injection in PCOS women, there are significant differences in LH reaction between the three groups with different glucose tolerance. Conclusion: Women with PCOS have more severe metabolic disturbance than women with T2DM except for systolic blood pressure. Insulin resistance affects the function of thalamus-pituitary-gonad axis.

Effects of resistant starch on behaviour, satiety-related hormones and metabolites in growing pigs

Resistant starch (RS) has been suggested to prolong satiety in adult pigs. The present study investigated RS-induced changes in behaviour, satiety-related hormones and metabolites in catheterized growing pigs to explore possible underlying mechanisms for RS-induced satiety. In a cross-over design with two 14-day periods, 10 pigs (initial BW: 58 kg) were assigned to two treatments comprising diets containing either 35% pregelatinized starch (PS) or 34% retrograded starch (RS). Diets were isoenergetic on gross energy. Pigs were fed at 2.8× maintenance. Postprandial plasma response of satiety-related hormones and metabolites was measured at the end of each period using frequent blood sampling. Faecal and urinary energy losses were measured at the end of each period. Behaviour was scored 24 h from video recordings using scan sampling. Energy digestibility and metabolizability were ~6% lower in RS compared with PS diet (P<0.001), and metabolizable energy (ME) intake was ~3% lower in RS-fed than in PS-fed pigs (P<0.001). RS-fed pigs showed less feeder-directed (P=0.001) and drinking (P=0.10) behaviours than PS-fed pigs throughout the day. Postprandial peripheral short-chain fatty acid (SCFA) levels were higher in RS-fed than in PS-fed pigs (P<0.001). Postprandial glucose and insulin responses were lower in RS-fed than in PS-fed pigs (P<0.001). Triglyceride levels were higher in RS-fed than in PS-fed pigs (P<0.01), and non-esterified fatty acid levels did not differ between diets (P=0.90). Glucagon-like peptide-1 (GLP-1) levels were lower in RS-fed than in PS-fed pigs (P<0.001), and peptide tyrosine tyrosine (PYY) levels did not differ between diets (P=0.90). Blood serotonin levels were lower (P<0.001), whereas monoamine oxidase activity (P<0.05) and tryptophan (P<0.01) levels were higher in RS-fed than in PS-fed pigs. Despite a lower ME intake, RS seemed to prolong satiety, based on behavioural observations. Possible underlying mechanisms for RS-induced satiety include increased 24 h plasma SCFA levels, and decreased postprandial glucose and insulin responses. GLP-1 and PYY seemed not to play a role in RS-induced satiety. Low blood serotonin levels in RS-fed pigs suggested a difference in intestinal serotonin release between treatments. Increased postprandial plasma triglyceride levels corresponded with increased SCFA levels, but it is unclear whether triglycerides may have signalled satiety in RS-fed pigs.