Postabsorptive Period Research Articles

Acute Effects of Cheddar Cheese Consumption on Circulating Amino Acids and Human Skeletal Muscle.

Cheddar cheese is a protein-dense whole food and high in leucine content. However, no information is known about the acute blood amino acid kinetics and protein anabolic effects in skeletal muscle in healthy adults. Therefore, we conducted a crossover study in which men and women (n = 24; ~27 years, ~23 kg/m2) consumed cheese (20 g protein) or an isonitrogenous amount of milk. Blood and skeletal muscle biopsies were taken before and during the post absorptive period following ingestion. We evaluated circulating essential and non-essential amino acids, insulin, and free fatty acids and examined skeletal muscle anabolism by mTORC1 cellular localization, intracellular signaling, and ribosomal profiling. We found that cheese ingestion had a slower yet more sustained branched-chain amino acid circulation appearance over the postprandial period peaking at ~120 min. Cheese also modestly stimulated mTORC1 signaling and increased membrane localization. Using ribosomal profiling we found that, though both milk and cheese stimulated a muscle anabolic program associated with mTORC1 signaling that was more evident with milk, mTORC1 signaling persisted with cheese while also inducing a lower insulinogenic response. We conclude that Cheddar cheese induced a sustained blood amino acid and moderate muscle mTORC1 response yet had a lower glycemic profile compared to milk.

Use of encapsulated L-lysine-HCl and DL-methionine improves postprandial amino acid balance in laying hens.

The supplementation of dietary limiting amino acids (AA) with crystalline AA makes the use of low-protein diets an option in poultry production. The differing absorption rates of crystalline and protein-bound AA may lead to temporally imbalanced AA in the postabsorptive period. In this study, two experiments were conducted to evaluate the effect of encapsulated L-lysine-HCl (L-Lys-HCl) and DL-methionine (DL-Met) on the laying performance of hens. In exp. 1, a total of 135 forty-seven-wk-old Hy-Line Brown hens were subjected to three dietary treatments for 8 wk: basal diet supplemented with 0.14% L-Lys-HCl and 0.17% DL-Met to satisfy the NRC (1994) total Lys and Met recommendation (control) and basal diet supplemented with encapsulated L-Lys-HCl and DL-Met at the levels of 60% (60CLM, 0.084% L-Lys-HCl and 0.102% DL-Met) or 80% of control (80CLM, 0.112% L-Lys-HCl and 0.136% DL-Met), respectively. In exp. 2, 24 fifty-five-wk-old Hy-Line Brown hens were individually reared in cages and subjected to the same treatments as in exp. 1. The plasma concentrations of free AA and nitrogen metabolites were measured 2, 4, and 6 h after fed. The results showed that dietary AA treatment had no significant influence on body weight (BW), feed intake, laying rate, egg weight, egg mass, or feed efficiency. The expression levels of AA transporters CAT-1, y+LAT1, b0,+AT, B0AT, rBAT, EAAT3, and PepT1 in the duodenum, jejunum, and ileum were not influenced (P > 0.05) by dietary treatment. There was an interaction of dietary AA treatment and time (P < 0.05) and the 80CLM hens exhibited higher concentrations of Lys (P < 0.05) than the controls at 2-h time point. In contrast, plasma Met concentration was not influenced (P > 0.05), while Cys was reduced in the 60CLM hens at every time point. The 80CLM hens had higher taurine concentrations than those receiving the control diet at every postprandial time point. In conclusion, these findings demonstrate that by using encapsulated form, the supplemental levels of synthetic L-Lys-HCl and DL-Met can be effectively reduced by approximately 20% with no negative effect on laying performance. The result suggests that encapsulated Lys and Met may ameliorate the postabsorptive AA balance and contribute to the reduced dietary AA supplemental levels.

Pre-sleep Or Post-exercise Protein Intake Does Not Augment Resistance Training Adaptations In Older Adults

Resistance training (RT) and protein consumption are recommended to attenuate decreases in muscle mass and strength with age. Immediate post-exercise (Post-ex) protein intake has been regarded as optimal for augmenting RT adaptations. However, nocturnal sleep is the longest post-absorptive period with muscle protein synthesis lower than basal rates. Thus, pre-sleep (Pre-sleep) protein intake may be more advantageous for older adults, who display blunted muscle anabolism, than Post-ex protein intake. PURPOSE: To examine the effects of pre-sleep versus post-exercise protein intake during 12 weeks of RT on muscle thickness (MT) and one-repetition maximum (1RM) strength in older adults. METHODS: 30 healthy, sedentary older males (age: 65.7±4.0 yrs, body mass: 85.9±13.1 kg) underwent the same 12-week whole-body RT program (2x/wk) and were randomly assigned to 1 of 3 groups, 1) consumed 40 g of protein immediately Post-ex (n=9), 2) consumed 40 g of protein 30 minutes Pre-sleep (n=11), or 3) did not consume additional protein supplementation (Ex only, n=10). MT was measured via ultrasound as the added values of the right rectus femoris, vastus intermedius, and vastus lateralis muscles. 1RM strength was assessed on the leg press machine. A 3x3 mixed-model ANOVA was used to analyze outcomes at pre-, mid-, and post-testing with significance at p≤0.05. RESULTS: There were significant main time effects for both MT (Pre: 6.29±0.98; Mid: 6.63±0.86; Post: 6.75±0.94 cm) and 1RM strength (Pre: 155.9±30.0; Mid: 170.1±36.0; Post: 184.2±47.1 kg). There were no group x time interactions or main group effects. Interestingly, only Post-ex significantly increased MT from pre to mid (Pre: 6.14±0.91; Mid: 6.67±0.88; Post 6.70±1.16 cm). CONCLUSION: During 12 weeks of RT in older adults, Post-ex protein intake increased MT in the first 6 weeks; however, after 12 weeks, improvements were similar to Pre-sleep protein intake and Ex only groups. Further, neither Post-ex nor Pre-sleep protein intake augmented RT-induced improvements in 1RM strength. Supported in part by Dymatize/ISSN Research Grant and Florida State University College of Human Sciences.

Sex-specific metabolic responses to 6 hours of fasting during the active phase in young mice.

Night time/active phase food restriction for 6 h impaired glucose intolerance in young male and female mice. Females displayed increased capacity for lipogenesis and triglyceride storage in response to a short daily fast. Females had lower fasting insulin levels and an increased potential for utilizing fat for energy through β-oxidation compared to males. The need for the inclusion of both sexes, and the treatment of sex as an independent variable, is emphasized within the context of this fasting regime. There is growing interest in understanding the mechanistic significance and benefits of fasting physiology in combating obesity. Increasing the fasting phase of a normal day can promote restoration and repair mechanisms that occur during the post-absorptive period. Most studies exploring the effect of restricting food access on mitigating obesity have done so with a large bias towards the use of male mice. Here, we disentangle the roles of sex, food intake and food withdrawal in the response to a short-term daily fasting intervention, in which food was removed for 6h in the dark/active phase of young, 8-week-old mice. We showed that the removal of food during the dark phase impaired glucose tolerance in males and females, possibly due to the circadian disruption induced by this feeding protocol. Although both sexes demonstrated similar patterns of food intake, body composition and various metabolic markers, there were clear sex differences in the magnitude and extent of these responses. While females displayed enhanced capacity for lipogenesis and triglyceride storage, they also had low fasting insulin levels and an increased potential for utilizing available energy sources such as fat for energy through β-oxidation. Our results highlight the intrinsic biological and metabolic disparities between male and female mice, emphasizing the growing need for the inclusion of both sexes in scientific research. Furthermore, our results illustrate sex-specific metabolic pathways that regulate lipogenesis, obesity and overall metabolic health.

Acute Response of Nutritive vs Non‐Nutritive Sweeteners in Sodas on Blood Glucose, Insulin and Levels of Satiety

Artificial sweeteners, both nutritive and non‐nutritive, are widely used in soft drinks and various food products in the United States. Claims have been made that non‐nutritive sweeteners used in a product like Diet Coke can have negative effects on blood sugar, satiety, and insulin release following consumption. However, the research on this is limited.PURPOSEThe purpose of this study was to evaluate the effects of a popular soda brand, both regular and diet, on how acute ingestion of these products affects blood glucose, insulin, and satiety levels.METHODSSixteen (age: 28.63 ± 5.55 yrs.; height: 169.75 ± 7.94 cm; weight: 84.65 ± 33.36 kg; body fat %: 19.49 ± 7.14 BF%; systolic BP: 115.94 ± 10.15 mm hg; diastolic BP: 68.97 ± 7.13 mm hg) males and females participated in this randomized, single‐blind crossover design. Participants reported to the lab fasted (10 hours) on two separate occasions and consumed either 24 fluid ounces of regular Coke (RC) or Diet Coke (DC) separated by one week. Fasting blood samples were obtained via venipuncture prior to consumption and participants remained in the lab in a rested state and had subsequent blood samples collected at 30, 60, 90 and 120‐minutes post‐ingestion. Satiety scale was administered at each time point prior to the blood collection. Glucose, insulin, and satiety were analyzed using 2 × 5 (condition × time) analysis of variance with repeated measures, follow‐up pairwise comparisons, and evaluation of partial eta‐squared (ηp2) effect sizes.RESULTSNo variables differed between conditions at baseline. Condition × time interactions were present for glucose (p=0.0001, ηp2=0.45) and insulin (p=0.0001, ηp2=0.42), but not satiety (p=0.80, ηp2=0.02). A time main effect (p=0.004, ηp2=0.32) was present for satiety. Follow‐up testing indicated that glucose concentration was significantly elevated 30 minutes after RC ingestion as compared to DC ingestion ([mean difference ± SE] 28.0 ± 4.6 mg/dL; p &lt;0.001), with no differences at other time points. In contrast, insulin concentrations were significantly higher at all post‐ingestion time points in the RC condition as compared to the DC condition (range: 3.6 ± 1.7 to 14.0 ± 1.7 μIU/mL; p ≤0.04 for all post‐ingestion time points). Satiety was significantly elevated at 30 minutes post‐ingestion (p=0.009) regardless of which drink was consumed but did not differ from baseline values for the remaining time points.CONCLUSIONIn conclusion, it appears that acute ingestion of RC increases both blood glucose and insulin levels in the post absorptive period with no differential effects than DC on levels of satiety. The significant sustained elevation in circulating insulin levels following the ingestion of a sugar sweetened beverage could lead to a sub‐optimal acute metabolic environment. This data suggests that acute consumption of non‐nutritive sweetened beverages does not have negative effects on blood glucose, insulin, or appetite in a healthy population and seems to be a better alternative to nutritive sweetened beverage options.Support or Funding InformationThis study was supported by a Graduate Faculty Research Grant at the University of Mary Hardin‐Baylor.

Basal and Postprandial Myofibrillar Protein Synthesis Rates Do Not Differ between Lean and Obese Middle-Aged Men

ABSTRACTBackgroundExcess lipid availability has been associated with the development of anabolic resistance. As such, obesity may be accompanied by impairments in muscle protein metabolism.ObjectiveWe hypothesized that basal and postprandial muscle protein synthesis rates are lower in obese than in lean men.MethodsTwelve obese men [mean ± SEM age: 48 ± 2 y; BMI (in kg/m2): 37.0 ± 1.5; body fat: 32 ± 2%] and 12 age-matched lean controls (age: 43 ± 3 y; BMI: 23.4 ± 0.4; body fat: 21 ± 1%) received primed continuous L-[ring-2H5]-phenylalanine and L-[ring-3,5-2H2]-tyrosine infusions and ingested 25 g intrinsically L-[1-13C]-phenylalanine labeled whey protein. Repeated blood and muscle samples were obtained to assess protein digestion and amino acid absorption kinetics, and basal and postprandial myofibrillar protein synthesis rates.ResultsExogenous phenylalanine appearance rates increased after protein ingestion in both groups (P < 0.001), with a total of 53 ± 1% and 53 ± 2% of dietary protein–derived phenylalanine appearing in the circulation over the 5-h postprandial period in lean and obese men, respectively (P = 0.82). After protein ingestion, whole-body protein synthesis and oxidation rates increased to a greater extent in lean men than in the obese (P-interaction < 0.05), resulting in a higher whole-body protein net balance in the lean than in the obese (7.1 ± 0.2 and 4.6 ± 0.4 µmol phenylalanine · h−1 · kg−1, respectively; P-interaction < 0.001). Myofibrillar protein synthesis rates increased from 0.030 ± 0.002 and 0.028 ± 0.003%/h in the postabsorptive period to 0.034 ± 0.002 and 0.035 ± 0.003%.h−1 in the 5-h postprandial period (P = 0.03) in lean and obese men, respectively, with no differences between groups (P-interaction = 0.58).ConclusionsBasal, postabsorptive myofibrillar protein synthesis rates do not differ between lean and obese middle-aged men. Postprandial protein handling, including protein digestion and amino acid absorption, and the postprandial muscle protein synthetic response after the ingestion of 25 g whey protein are not impaired in obese men. This trial was registered at www.trialregister.nl as NTR4060.

Metabolic and Inflammatory Effects of an ω-3 Fatty Acid-Based Eucaloric Ketogenic Diet in Mice With Endotoxemia.

Dietary strategies can aid in the management of critically ill patients. Very-low-carbohydrate diets have been shown to improve glucose control and the inflammatory response. We aimed to determine the effects of a eucaloric ketogenic diet (EKD) enriched with ω-3 fatty acids (O3KD) on glucose levels and inflammation in mice with endotoxemia. Adult mice were fed 1 of 3 diets (control diet [CD], EKD, or O3KD). After 4 weeks, each group received saline or Escherichia coli lipopolysaccharide (LPS) (5 mg/kg) intraperitoneally during the postprandial (PPP) or postabsorptive (PAP) periods. Blood glucose was measured at 0, 15, 30, 60, 90, 120, 180, and 240 minutes. Serum tumor necrosis factor (TNF)-α and interleukin (IL) 6 were measured by enzyme-linked immunosorbent assay. Distribution of serum fatty acids was determined by gas liquid chromatography. Hepatic expression of genes involved in inflammation, as well as glucose and lipid metabolism, were determined by quantitative polymerase chain reaction. During the PPP, glucose curves were comparable among the experimental groups. During the PAP, EKD showed a more pronounced increase in glucose levels at the first hour after LPS challenge compared with the CD-LPS group. During the PAP, IL6 was lower in O3KD-LPS compared with CD-LPS and EKD-LPS groups. These differences disappeared in the PPP. Similarly, TNF-α was lower in the O3KD-LPS group compared with the EKD-LPS group. The O3KD significantly increased the serum levels of the ω-3 eicosapentaenoic and docosahexaenoic acids and decreased the ω-6 arachidonic acid. An O3KD leads to reduced inflammation and maintains glucose homeostasis in mice with endotoxemia.

The role of intermittent fasting and meal timing in weight management and metabolic health.

Obesity remains a major public health concern and intermittent fasting is a popular strategy for weight loss, which may present independent health benefits. However, the number of diet books advising how fasting can be incorporated into our daily lives is several orders of magnitude greater than the number of trials examining whether fasting should be encouraged at all. This review will consider the state of current understanding regarding various forms of intermittent fasting (e.g. 5:2, time-restricted feeding and alternate-day fasting). The efficacy of these temporally defined approaches appears broadly equivalent to that of standard daily energy restriction, although many of these models of intermittent fasting do not involve fed-fasted cycles every other 24 h sleep-wake cycle and/or permit some limited energy intake outside of prescribed feeding times. Accordingly, the intervention period therefore may not regularly alternate, may not span all or even most of any given day, and may not even involve absolute fasting. This is important because potentially advantageous physiological mechanisms may only be initiated if a post-absorptive state is sustained by uninterrupted fasting for a more prolonged duration than applied in many trials. Indeed, promising effects on fat mass and insulin sensitivity have been reported when fasting duration is routinely extended beyond sixteen consecutive hours. Further progress will require such models to be tested with appropriate controls to isolate whether any possible health effects of intermittent fasting are primarily attributable to regularly protracted post-absorptive periods, or simply to the net negative energy balance indirectly elicited by any form of dietary restriction.

Consistency of Continuous Ambulatory Interstitial Glucose Monitoring Sensors.

Aims: The abdominal region is the most common location for continuous glucose monitor (CGM) sensor insertion. However, a paucity of post-marketing data is available to demonstrate intra-individual consistency of CGM readings at different abdominal insertion sites. Methods: Healthy adults (fasting glucose (FG) < 5.5 mmol/L; BMI < 30 kg/m2) were recruited and a CGM sensor was placed on each side of the abdomen. Postprandial and continuous 48-h interstitial glucose levels were analyzed. Results: There was no significant difference in the 3-h postprandial glucose (PPG) level derived from the left versus right CGM, which remained non-significant after adjusting for waist circumference or FG. Among the glucose levels recorded over 48-h, values on the left site were greater in 3.6% of the data points (p < 0.05). After adjusting for waist circumference, only 0.5% of the glucose values remained significantly greater on the left (p < 0.05). When adjusted for FG, similar results were observed. For both PPG and 48-h readings, the mean absolute relative difference was not significant between the two abdominal sites. Conclusions: CGM-derived glucose measures were highly consistent between the left and right abdomen during both the postprandial and post-absorptive periods.

The role of the kidneys in glucose homeostasis

Until recently, in was believed that degradation of insulin is the main function of the kidneys in maintaining glucose homeostasis. The results of numerous studies showed that the kidneys are involved in filling the energy needs of the body due to the following three key processes: gluconeogenesis, uptake and reabsorption of glucose molecules. The characteristic feature of gluconeogenesis that occurs in the kidneys lies in the fact that it depends on the time elapsed since the last meal. Thus, gluconeogenesis that occurs in the cortical substance of the kidneys provides up to 90% of the glucose entering the blood in the post-absorptive period and up to 60% in the postprandial period. Glucose reabsorption from the glomerular filtrate occurs in the proximal convoluted tubules assisted by sodium-glucose cotransporters, sodium-glucose cotransporters 2 (SGLT2) being the most important of them. It is known that the cells of the proximal convoluted tubules of the kidneys in patients with type 2 diabetes mellitus (DM2) contain significantly more SGLT2 proteins compared to those of healthy individuals. The discovery of the important role of the kidneys in glucose homeostasis led to investigation of the new links in DM2 pathogenesis and the development of a promising approach to its treatment using SGLT2 inhibitors.

Long-term intake of saccharin decreases post-absortive energy expenditure at rest and is associated to greater weight gain relative to sucrose in wistar rats

BackgroundNon-nutritive sweeteners (NNS) have been associated with increased prevalence of obesity. In previous studies, we demonstrated that saccharin could induce an increase in weight gain either when compared to sucrose or to a non-sweetened control at a similar total caloric intake. These data raised the hypothesis that reduced energy expenditure (EE) could be a potential mechanism explaining greater weight gain with saccharin use in rats. The aim of the present study was to compare long-term energy expenditure at rest between rats using saccharin or sucrose and correlate it with weight gain. MethodsIn the present study, we examine the potential impact of saccharin compared to sucrose in the EE of Wistar rats. In a controlled experiment of 17 weeks, 24 Wistar rats were divided into 2 groups: saccharin-sweetened yogurt (SAC) or sucrose-sweetened yogurt (SUC), plus a free chow diet. Only rats that consumed at least 70% of the offered yogurt were included. EE (kcal/day) was determined at rest through open circuit indirect calorimetry system in the early post-absorptive period with determinations of both VO2 consumption and CO2 production. Measurements were evaluated at baseline, 5 and 12 weeks of dietary intervention. Weight gain, caloric intake (from yogurt, from chow and total) were determined weekly.ResultsBody weight and EE were similar between groups at baseline: (p = .35) and (p = .67) respectively. At the end of the study, SAC increased total weight gain significantly more in relation to SUC (p = .03). Cumulative total caloric intake (yogurt plus chow) was similar between groups during the whole period (p = .54). At 12 weeks, the EE was smaller in SAC compared to SUC (p = .009). Considering both groups, there was a strong negative correlation between total weight gain and change in EE observed [r(20) = −.61, p = .003]. However, when analyzing the groups separately we found that SUC maintained this inverse correlation [r(8) = −.68, p = .03], while SAC did not [r(10) = −.33, p = .29].ConclusionThese data support the hypothesis that long-term use of saccharin may blunt post-absorptive EE at rest in Wistar rats, which is related to weight gain. On the other hand, long-term sucrose intake can increase energy expenditure in rats. This effect combined can explain, at least partially, the weight gain increases associated to saccharin in relation to sucrose in these animals.

The Individual Meal Pattern

in Mean BG but significantly different from all other strata. We might say that each subject is imprisoned in his/her own stratum and maintains a steady meal pattern to maintain a steady BG. Figure 1 shows Mean BGs in increasing sequence: The high Mean BGs are associated with insulin resistance. These assessments on Mean BG were taken before any training on Initial Hunger (IH) and again after 5 months from training. I was criticized by ASN for assessments based on portable devices. Portable devices are unreliable. When I started my long research, I considered single BG measurements as inconsistent and the BG wavering destitute any meaning to the measurements. The liver delivers glucose into blood every 12 minutes. Physical activity, a gram of sugar, a heavy concern, all increase BG. We do not know the onset of the post-absorptive period, that also declines lowly, slowly. I retained that we could better rely on the mean of many measurements during a period. Single measurements were incorporated in collective, weekly assessments (Mean BG). At recruitment, the BG means of 120 investigated subjects showed SDs of 5 to 10 mg/dL that corresponded to confidence limits of 3.84 mg/dL at P < 0.05. We could stratify the 120 subjects in ten small strata. Each stratum contained subjects without differences

Eucaloric Ketogenic Diet Reduces Hypoglycemia and Inflammation in Mice with Endotoxemia.

Dietary strategies to alter the immune response to acute inflammation have the potential to improve outcomes in critically ill patients. A eucaloric ketogenic diet (EKD), composed predominantly of fat with very small amounts of carbohydrate, can provide adequate caloric support while minimizing spikes in blood glucose and reducing oxidative stress. The purpose of this study was to evaluate the effects of an EKD on glycemic control and the inflammatory response after acute endotoxemia in mice. Mice received either an EKD or a carbohydrate-based control diet (CD) for 4weeks. Animals subsequently underwent either a 2-h fast (postprandial) or an overnight fast (postabsorptive), and half of the animals in each diet group were randomized to receive either intraperitoneal lipopolysaccharide (1mg/kg) or an equivalent volume of saline. Glycemic response, insulin resistance, inflammatory cytokine levels, and the expression of key inflammatory and metabolic genes were measured. After endotoxin challenge, hypoglycemia was more frequent in mice fed a CD than an EKD in the postprandial period. This was due in part to the preservation of hepatic glycogen stores despite endotoxin exposure and prolonged fasting in mice fed an EKD. Furthermore, mice fed the CD had higher levels of IL-6 and TNF-α in the postabsorptive period, with a fivefold higher expression of hepatic NFκB compared to mice fed the EKD in both fasting periods. These results suggest that the unique metabolic state induced by an EKD can alter the response to acute inflammation in mice.

Quantitative determination of FAM3D plasma protein in type 2 diabetes mellitus

Background Among the new cytokine Family with Sequence Similarity 3 (FAM3), a subfamily of proteins similar to cytokines known as FAM3D was identified. FAM3D is predominantly expressed in the gastrointestinal tract of normal individuals. Plasma concentrations of FAM3D range according to the nutritional status presenting a postprandial increase and a reduction in the later postabsorptive period. It might be speculated that FAM3D is an inhibitor of insulin secretion, as it has been observed a significant increase in patients with pancreatic adenocarcinoma associated with T2D.

Efeito de 12 semanas de treinamento aeróbio em jejum sobre o emagrecimento

This study aimed to verify 12 weeks of aerobic training effect on fasting weight loss performed between October 2014 and March 2015 at Pitagoras a city in Betim/MG. The sample was 33 sedentary women without metabolic diseases. Initially the volunteers were submitted to aerobic capacity test (Balke-Ware) and body composition evaluation. It was recorded the total body mass (TBM), muscle mass (MM), fat mass (FM) and percentage of body fat (PBF) by tetrapolar bioimpedance. Then the volunteers were randomly divided into three groups, who performed aerobic training in a treadmill. One group performed the training in fasting (FT) in the post-absorptive period, with low intensity (50% of the heart rate reserve), while another group performed the same training, but in fed state (PT). The third group ran the same distance from the other groups, but with higher intensity (HIT) (70% of the heart rate reserve) in fed state. To compare body composition and aerobic capacity before and after training it was used the paired t test, while to compare the percentage change of MCT and the PGC between groups it was used the ANOVA one-way test. The results showed that the aerobic capacity increased in all groups, but the increase was greater in the HIT. Further, the HIT presented a significant reduction in FM and PBF, while the FT and PT groups showed no significant changes in body composition. No significant differences were found between the groups in relation to variation of PGC and PBF. It was concluded that fasted aerobic training has no additional effect on weight loss.

Glucagon-Like Peptide 2 (GLP-2) Stimulates Postprandial Chylomicron Production and Postabsorptive Release of Intestinal Triglyceride Storage Pools via Induction of Nitric Oxide Signaling in Male Hamsters and Mice.

The intestinal overproduction of apolipoprotein B48 (apoB48)-containing chylomicron particles is a common feature of diabetic dyslipidemia and contributes to cardiovascular risk in insulin resistant states. We previously reported that glucagon-like peptide-2 (GLP-2) is a key endocrine stimulator of enterocyte fat absorption and chylomicron output in the postprandial state. GLP-2's stimulatory effect on chylomicron production in the postabsorptive state has been confirmed in human studies. The mechanism by which GLP-2 regulates chylomicron production is unclear, because its receptor is not expressed on enterocytes. We provide evidence for a key role of nitric oxide (NO) in mediating the stimulatory effects of GLP-2 during the postprandial and postabsorptive periods. Intestinal chylomicron production was assessed in GLP-2-treated hamsters administered the pan-specific NO synthase (NOS) inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), and in GLP-2-treated endothelial NOS knockout mice. L-NAME blocked GLP-2-stimulated apoB48 secretion and reduced triglycerides (TGs) in the TG-rich lipoprotein (TRL) fraction of the plasma in the postprandial state. Endothelial NOS-deficient mice were resistant to GLP-2 stimulation and secreted fewer large apoB48-particles. When TG storage pools were allowed to accumulate, L-NAME mitigated the GLP-2-mediated increase in TRL-TG, suggesting that NO is required for early mobilization and secretion of stored TG and preformed chylomicrons. Importantly, the NO donor S-nitroso-L-glutathione was able to elicit an increase in TRL-TG in vivo and stimulate chylomicron release in vitro in primary enterocytes. We describe a novel role for GLP-2-mediated NO-signaling as a critical regulator of intestinal lipid handling and a potential contributor to postprandial dyslipidemia.

Muscle p70S6K phosphorylation in response to soy and dairy rich meals in middle aged men with metabolic syndrome: a randomised crossover trial.

BackgroundThe mammalian target of rapamycin (mTOR) pathway is the primary regulator of muscle protein synthesis. Metabolic syndrome (MetS) is characterized by central obesity and insulin resistance; little is known about how MetS affects the sensitivity of the mTOR pathway to feeding.MethodsThe responsiveness of mTOR pathway targets such as p706Sk to a high protein meal containing either dairy or soy foods was investigated in healthy insulin sensitive middle-aged men and those presenting with metabolic syndrome (MetS). Twenty male subjects (10 healthy controls, 10 MetS) participated in a single-blinded randomized cross-over study. In a random sequence, subjects ingested energy-matched breakfasts composed predominately of either dairy-protein or soy-protein foods. Skeletal muscle biopsies were collected in the fasted state and at 2 and 4 h post-meal ingestion for the analysis of mTOR- and insulin-signalling kinase activation.ResultsPhosphorylated Akt and Insulin receptor substrate 1 (IRS1) increased during the postabsorptive period with no difference between groups. mTOR (Ser448) and ribosomal protein S6 phosphorylation increased 2 h following dairy meal consumption only. p70S6K (Thr389) phosphorylation was increased after feeding only in the control subjects and not in the MetS group.ConclusionsThese data demonstrate that the consumption of a dairy-protein rich but not a soy-protein rich breakfast activates the phosphorylation of mTOR and ribosomal protein S6, required for protein synthesis in human skeletal muscle. Unlike healthy controls, subjects with MetS did not increase muscle p70S6K(Thr389) phosphorylation in response to a mixed meal.Trial registrationThis trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) as ACTRN12610000562077.

“Fast proteins” with a unique essential amino acid content as an optimal nutrition in the elderly: Growing evidence

Adequate protein intake is crucial to maintain body protein content in elderly subjects, but quality of dietary proteins should be also considered since amino acid composition and rate of protein digestion modulate amino acid availability. This study investigates whether the efficacy of optimal protein intake levels for protein retention in the elderly is influenced by protein quality. We investigated the effect of a 10-day adequate-protein (AP) or high-protein (HP) diet together with the protein source as caseins (CAS) or soluble milk proteins (PRO) on whole-body (WB) protein synthesis (PS) and protein breakdown (PB) in 4 groups of healthy elderly men (mean ± SEM: 71.8 ± 24.4 yr). The study consisted of two periods of 4 h each: a post-absorptive period and a postprandial period. The fed state was defined by consumption every 20 min and for 4 h, of either 15 g or 30 g of PRO or CAS. Steady-state WB and splanchnic leucine kinetics were measured using a continuous infusion of L-[1-13C]leucine in the postabsorptive state and L-[1-13C]leucine infusion plus oral L-[5,5,5-2H3]leucine in the postprandial state. WB PS was stimulated by feeding only with HP diets, whereas WB PB corrected for splanchnic extraction showed a similar pattern of post-feeding decrease in all groups. Consequently, net leucine balance was greater in the postprandial state after HP meals than after AP meals, with PRO meals leading to a better postprandial leucine balance (3.63 ± 0.16 μmol kg FFM(-1) min(-1)vs. 2.77 ± 0.21 μmol kg FFM(-1) min(-1) for PRO HP and CAS HP, respectively; P = 0.005). Postprandial protein retention was better improved in elderly men by an increase in protein intake when the protein supplementation was provided as fast-digesting proteins that induce high leucine availability.

Effects of leucine and its metabolite β‐hydroxy‐β‐methylbutyrate on human skeletal muscle protein metabolism

Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses–fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is ‘sensed’ have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-13C2]Leu and [2H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A–V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70%vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling ≤90 min vs. ≤30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; −57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu.

Role of pituitary in K+ homeostasis: impaired renal responses to altered K+ intake in hypophysectomized rats

The kidneys maintain extracellular K⁺ homeostasis by altering K⁺ excretion to match K⁺ intake. Because this can occur without changes in plasma K⁺ concentrations ([K⁺]), how the kidneys sense K⁺ intake is unclear. We tested the hypothesis that the pituitary plays a critical role in signaling K⁺ intake to the kidneys. If this hypothesis is true, hypophysectomy would impair kidney responses to altered K⁺ intake. Hypophysectomized (Hypox) and sham-operated control rats (n = 8 each) were compared for their abilities to adjust K⁺ excretion during a transition from normal to reduced (to one-third of normal) K⁺ intake, followed by a reversal to normal K⁺ intake. Food was provided only at night, and renal K⁺ excretion was determined both for absorptive (night or feeding) and postabsorptive (day or nonfeeding) periods. In normal rats, both absorptive and postabsorptive renal K⁺ excretion were changed in parallel to the changes in K⁺ intake, indicating a rapid adaptation of normal kidneys to altered K⁺ intake. In Hypox rats, whereas absorptive renal K⁺ excretion was changed in response to changes in K⁺ intake, postabsorptive K⁺ excretion was not responsive (P < 0.001), indicating impaired renal responses to altered K⁺ intake. In addition, Hypox rats, compared with control rats, showed K⁺ intolerance (increases in plasma [K⁺]) upon feeding (i.e., K⁺ intake) at night or following an intravenous K⁺ infusion (P < 0.01), indicating an impairment of acute renal responses to K⁺ intake. These data support that the pituitary plays a key role in the signaling of K⁺ intake to the kidneys (and kidney responses to altered K⁺ intake).