Postabsorptive State Research Articles

Towards a dynamic model of indispensable amino acid requirements of the adult human: A factorial estimate of oxidative amino acid losses

BackgroundConsensus regarding the required intake of indispensable amino acids (IDAAs) and protein (representing total AAs) in the adult is lacking. Oxidation is a major, though not exclusive, source of IDAA loss in the human body and a primary factor determining requirements; a quantitative understanding of oxidative IDAA losses is required. ObjectiveTo develop a factorial diurnal model of total oxidative IDAA and protein losses in the adult human. MethodsA factorial diurnal model of oxidative losses of protein and each IDAA at maintenance was developed by estimating the magnitude and variability of sources of oxidative loss from existing literature: inevitable catabolism (constitutive oxidation of each absorbed dietary AA), and protein turnover in the postprandial and postabsorptive states. Total oxidative losses were calculated by summing individual losses, validated against published independent nitrogen balance data and compared to current IDAA requirements. ResultsThe factorial model predicted minimum oxidative total AA losses of 390±60 mg.kgBW-1.day-1, 59% of the EAR for protein. Inevitable AA oxidation and oxidation associated with postabsorptive protein turnover were the major sources of the oxidative loss for protein, at 40% and 44%, respectively. Summed oxidative IDAA losses ranged from 64% (isoleucine) to 91% (tryptophan) of current requirements. Total oxidative losses predicted by the model were significant predictors of actual experimental oxidative losses obtained by nitrogen balance (R2=0.66; p=0.049). ConclusionsThe use of a factorial model for estimation of minimum IDAA and protein oxidative losses in the adult human provides an essential starting point for an updated understanding of protein and IDAA requirements. Further iterations of the model will estimate total protein and IDAA requirements, and account for variations in dietary protein quantity and quality, as well as different populations and physiological states. Additional data, especially for inevitable oxidation in humans, and particularly with respect to individual IDAAs, are needed.

Metabolic Compensation Associated With Digestion in Response to the Latitudinal Thermal Environment Across Populations of the Prairie Lizard (Sceloporus consobrinus).

Environmental temperatures directly affect physiological rates in ectotherms by constraining the possible body temperatures they can achieve, with physiological processes slowing as temperatures decrease and accelerating as temperatures increase. As environmental constraints increase, as they do northward along the latitudinal thermal gradient, organisms must adapt to compensate for the slower physiological processes or decreased opportunity time. Evolving faster general metabolic rates is one adaptive response posited by the metabolic cold adaptation (MCA) hypothesis. Here we test the MCA hypothesis by examining metabolism of prairie lizard populations across the latitudinal thermal gradient. Our results show that populations from cooler environments have higher standard metabolic rates (SMRs), but these are explained by associated larger body sizes. However, metabolic rates of fed, postprandial individuals (MRFed) and metabolic energy allocated to digestion (MRΔ) were highest in the population from the coldest environment after accounting for the effect of body size. Our results suggest cold-adapted populations compensate for lower temperatures and shorter activity periods by increasing metabolic rates associated with physiological processes and thus support the MCA hypothesis. When examining energy expenditure, metabolic rates of individuals in a postprandial state (MRFed) may be more ecologically relevant than those in a postabsorptive state (SMR) and give a better picture of energy use in ectotherm populations.

High-Moisture Extrusion of a Dietary Protein Blend Impairs In Vitro Digestion and Delays In Vivo Postprandial Plasma Amino Acid Availability in Humans

BackgroundIndustrial processing can alter the structural complexity of dietary proteins and, potentially, their digestion and absorption upon ingestion. High-moisture extrusion (HME), a common processing method used to produce meat alternative products, affects in vitro digestion, but human data are lacking. We hypothesized that HME of a mycoprotein/pea protein blend would impair in vitro digestion and in vivo postprandial plasma amino acid availability. MethodsIn Study A, 9 healthy volunteers completed 2 experimental trials in a randomized, double-blind, crossover design. Participants consumed a beverage containing 25 g protein from a “dry” blend (CON) of mycoprotein/pea protein (39%/61%) or an HME content-matched blend (EXT). Arterialized venous blood samples were collected in the postabsorptive state and regularly over a 5-h postprandial period to assess plasma amino acid concentrations. In Study B, in vitro digestibility of the 2 beverages were assessed using bicinchoninic acid assay and optical fluorescence microscopy at baseline and during and following gastric and intestinal digestion using the INFOGEST model of digestion. ResultsProtein ingestion increased plasma total, essential (EAA), and branched-chain amino acid (BCAA) concentrations (time effect, P < 0.0001) but more rapidly and to a greater magnitude in the CON compared with the EXT condition (condition × time interaction, P < 0.0001). This resulted in greater plasma availability of EAA and BCAA concentrations during the early postprandial period (0–150 min). These data were corroborated by the in vitro approach, which showed greater protein availability in the CON (2150 ± 129 mg/mL) compared with the EXT (590 ± 41 mg/mL) condition during the gastric phase. Fluorescence microscopy revealed clear structural differences between the 2 conditions. ConclusionsThese data demonstrate that HME delays in vivo plasma amino acid availability following ingestion of a mycoprotein/pea protein blend. This is likely due to impaired gastric phase digestion as a result of HME-induced aggregate formation in the pea protein.This trial was registered at clinicaltrials.gov as NCT05584358.

Quantification and interpretation of postprandial whole-body protein metabolism using stable isotope methodology: a narrative review.

Stable isotopes are routinely applied to determine the impact of factors such as aging, disease, exercise, and feeding on whole-body protein metabolism. The most common approaches to quantify whole-body protein synthesis, breakdown, and oxidation rates and net protein balance are based on the quantification of plasma amino acid kinetics. In the postabsorptive state, plasma amino acid kinetics can easily be assessed using a constant infusion of one or more stable isotope labeled amino acid tracers. In the postprandial state, there is an exogenous, dietary protein-derived amino acid flux that needs to be accounted for. To accurately quantify both endogenous as well as exogenous (protein-derived) amino acid release in the circulation, the continuous tracer infusion method should be accompanied by the ingestion of intrinsically labeled protein. However, the production of labeled protein is too expensive and labor intensive for use in more routine research studies. Alternative approaches have either assumed that 100% of exogenous amino acids are released in the circulation or applied an estimated percentage based on protein digestibility. However, such estimations can introduce large artifacts in the assessment of whole-body protein metabolism. The preferred estimation approach is based on the extrapolation of intrinsically labeled protein-derived plasma bioavailability data obtained in a similar experimental design setting. Here, we provide reference data on exogenous plasma amino acid release that can be applied to allow a more accurate routine assessment of postprandial protein metabolism. More work in this area is needed to provide a more extensive reference data set.

Compartmental analysis: a new approach to estimate protein breakdown and meal response in health and critical illness.

This study aimed to discuss the use of the pulse stable isotope tracer approach to study changes in metabolism in healthy individuals and critically ill patients. We found that in the postabsorptive state and healthy condition, intracellular protein breakdown and net intracellular protein breakdown, when calculated using the pulse tracer approach, are about double what has previously been reported using the more traditional primed-constant and continuous stable isotope approaches (600 versus 300 grams of protein/day). In critically ill patients, protein breakdown is even higher and calculated to be approximately 900 grams of protein/day, using the pulse tracer approach. Based on these data, we hypothesize that reducing protein breakdown in the postabsorptive state is key when trying to improve the condition of critically ill patients. Moreover, we also used the pulse tracer approach during feeding to better estimate the intracellular metabolic response to feeding. Our first observation is that endogenous protein breakdown does not seem to be reduced during feeding. We also have shown that when consuming a meal with a certain amount of protein, the biological value of that protein meal can be calculated with the pulse tracer approach. In conclusion, using the pulse stable isotope tracer approach to study protein kinetics in the postabsorptive state and during feeding expands our understanding of how dietary proteins can affect human protein metabolism. The intracellular protein synthesis stimulatory effect of a meal is an important factor to consider when calculating the exact protein requirements and needs, particularly in critical illness.

Postprandial Increase of Adenosine 2B Receptor in Adipose Tissue Promotes Lipotoxicity

Obese adipose tissue is known to have higher basal rates of lipolysis than lean adipose tissue. This chronic outflow of lipids leads to the ectopic deposition of lipids into non-adipose, insulin-sensitive tissues such as the heart, liver, and skeletal muscle. This process, known as lipotoxicty, promotes the development of insulin resistance in these tissues. Therefor developing ways to control lipolysis in obese individuals is a useful intervention that would help curtail the development of type II diabetes. Adenosine, a nucleoside released from cells during metabolic stress or inflammation, may play an important role in this process. Our lab has discovered that adipocytes tightly regulate Adenosine receptor 2B (A2BR) expression during the transition from the postabsorptive (fasting) to postprandial (fed) state. QPCR data has confirmed that A2BR levels increase postprandially and decrease postabsorptively in adipose tissue, but not other insulin-sensitive organs. Administration of an A2BR agonist in mice yields a large lipolytic response in the postprandial, but not postabsorptive state. Genetic deletion of A2BR from adipose tissue confirms that this lipolytic response depends on A2BR signaling in the individual adipocytes. Importantly we have also shown that A2BR levels in obese mouse adipose tissue are constitutively high regardless of nutritional state, suggesting these cells are primed for lipolytic stimulation. Therefore, pharmacological antagonists of A2BR could reduce basal lipolysis in obese individuals and in turn improve whole body insulin sensitivity. 5T32GM139787-03 5R01GM136900-04. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute effects of a ketone monoester, whey protein, or their coingestion on mTOR trafficking and protein-protein colocalization in human skeletal muscle.

We recently demonstrated that acute oral ketone monoester intake induces a stimulation of postprandial myofibrillar protein synthesis rates comparable to that elicited following the ingestion of 10 g whey protein or their coingestion. The present investigation aimed to determine the acute effects of ingesting a ketone monoester, whey protein, or their coingestion on mechanistic target of rapamycin (mTOR)-related protein-protein colocalization and intracellular trafficking in human skeletal muscle. In a randomized, double-blind, parallel group design, 36 healthy recreationally active young males (age: 24.2 ± 4.1 yr) ingested either: 1) 0.36 g·kg-1 bodyweight of the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET + PRO). Muscle biopsies were obtained in the overnight postabsorptive state (basal conditions), and at 120 and 300 min in the postprandial period for immunofluorescence assessment of protein translocation and colocalization of mTOR-related signaling molecules. All treatments resulted in a significant (Interaction: P < 0.0001) decrease in tuberous sclerosis complex 2 (TSC2)-Ras homolog enriched in brain (Rheb) colocalization at 120 min versus basal; however, the decrease was sustained at 300 min versus basal (P < 0.0001) only in KET + PRO. PRO and KET + PRO increased (Interaction: P < 0.0001) mTOR-Rheb colocalization at 120 min versus basal; however, KET + PRO resulted in a sustained increase in mTOR-Rheb colocalization at 300 min that was greater than KET and PRO. Treatment intake increased mTOR-wheat germ agglutinin (WGA) colocalization at 120 and 300 min (Time: P = 0.0031), suggesting translocation toward the fiber periphery. These findings demonstrate that ketone monoester intake can influence the spatial mechanisms involved in the regulation of mTORC1 in human skeletal muscle.NEW & NOTEWORTHY We explored the effects of a ketone monoester (KET), whey protein (PRO), or their coingestion (KET + PRO) on mTOR-related protein-protein colocalization and intracellular trafficking in human muscle. All treatments decreased TSC2-Rheb colocalization at 120 minutes; however, KET + PRO sustained the decrease at 300 min. Only PRO and KET + PRO increased mTOR-Rheb colocalization; however, the increase at 300 min was greater in KET + PRO. Treatment intake increased mTOR-WGA colocalization, suggesting translocation to the fiber periphery. Ketone bodies influence the spatial regulation of mTOR.

Acute ingestion of a ketone monoester, whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of myofibrillar protein synthesis rates in young males: a double-blind randomized trial

BackgroundKetone bodies may have anabolic effects in skeletal muscle via their capacity to stimulate protein synthesis. Whether orally ingested exogenous ketones can stimulate postprandial myofibrillar protein synthesis (MyoPS) rates with and without dietary protein co-ingestion is unknown. ObjectivesThis study aimed to evaluate the effects of ketone monoester intake and elevated blood β-hydroxybutyrate (β-OHB) concentration, with and without dietary protein co-ingestion, on postprandial MyoPS rates and mechanistic target of rapamycin complex 1 (mTORC1) pathway signaling. MethodsIn a randomized, double-blind, parallel group design, 36 recreationally active healthy young males (age: 24.2 ± 4.1 y; body fat: 20.9% ± 5.8%; body mass index: 23.4 ± 2 kg/m2) received a primed continuous infusion of L-[ring-2H5]-phenylalanine and ingested one of the following: 1) the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET+PRO). Blood and muscle biopsy samples were collected during basal and postprandial (300 min) conditions to assess β-OHB, glucose, insulin, and amino acid concentrations, MyoPS rates, and mTORC1 pathway signaling. ResultsCapillary blood β-OHB concentration increased similarly during postprandial conditions in KET and KET+PRO, with both being greater than PRO from 30 to 180 min (treatment × time interaction: P < 0.001). Postprandial plasma leucine and essential amino acid (EAA) incremental area under the curve (iAUC) over 300 min was greater (treatment: both P < 0.001) in KET+PRO compared with PRO and KET. KET, PRO, and KET+PRO stimulated postprandial MyoPS rates (0–300 min) higher than basal conditions [absolute change: 0.020%/h; (95% CI: 0.013, 0.027%/h), 0.014%/h (95% CI: 0.009, 0.019%/h), 0.019%/h (95% CI: 0.014, 0.024%/h), respectively (time: P < 0.001)], with no difference between treatments (treatment: P = 0.383) or treatment × time interaction (interaction: P = 0.245). mTORC1 pathway signaling responses did not differ between treatments (all P > 0.05). ConclusionsAcute oral intake of a ketone monoester, 10 g whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of postprandial MyoPS rates in healthy young males.This trial was registered at clinicaltrials.gov as NCT04565444 (https://clinicaltrials.gov/study/NCT04565444).

Nasogastric bolus administration of a protein-rich drink augments insulinaemia and aminoacidaemia but not whole-body protein turnover or muscle protein synthesis versus oral administration.

Nasogastric feeding of protein-rich liquids is a nutritional support therapy that attenuates muscle mass loss. However, whether administration via a nasogastric tube per se augments whole-body or muscle protein anabolism compared with oral administration is unknown. Healthy participants were administered a protein-rich drink (225 ml containing 21 g protein) orally (ORAL; n=13; age 21 ± 1 year; BMI 22.2 ± 0.6 kg·m-2) or via a nasogastric tube (NG; n=13; age 21 ± 1 yr; BMI 23.9 ± 0.9 kg·m-2) in a parallel group design, balanced for sex. L-[ring-2H5]-phenylalanine and L-[3,3-2H2]-tyrosine were infused to measure postabsorptive and postprandial whole-body protein turnover. Skeletal muscle biopsies were collected at -120, 0, 120 and 300 min relative to drink administration to quantify temporal myofibrillar fractional synthetic rates (myoFSR). Drink administration increased serum insulin and plasma amino acid concentrations, and to a greater extent and duration in NG versus ORAL (all interactions P<0.05). Drink administration increased whole-body protein synthesis (P<0.01), suppressed protein breakdown (P<0.001), and created positive net protein balance (P<0.001), but to a similar degree in ORAL and NG (interactions P>0.05). Drink administration increased myoFSR from the postabsorptive state (P<0.01), regardless of route of administration in ORAL and in NG (interaction P>0.05). Nasogastric bolus administration of a protein-rich drink induces insulinaemia and aminoacidaemia to a greater extent than oral administration, but the postprandial increase in whole-body protein turnover and muscle protein synthesis was equivalent between administration routes. Nasogastric administration is a potent intervention to increase postprandial amino acid availability. Future work should assess its utility in overcoming impaired sensitivity to protein feeding, such as that seen in ageing, disuse, and critical care.

Characterisation of the Muscle Protein Synthetic Response to Resistance Exercise in Healthy Adults: A Systematic Review and Exploratory Meta-Analysis.

Five electronic databases (PubMed (Medline), Web of Science, Embase, Sport Discus, and Cochrane Library) were searched for controlled trials that assessed the MPS response to RE in healthy, adult humans, postabsorptive state. Individual study and random-effects meta-analysis arewere used to inform the effects of RE and covariates on MPS. Results from 79 controlled trials with 237 participants were analysed. Analysis of the pooled effects revealed robust increases in MPS following RE (weighted mean difference (WMD): 0.032% h-1, 95% CI: [0.024, 0.041] % h-1, I2 = 92%, k = 37, P < 0.001). However, the magnitude of the increase in MPS was lower in older adults (>50 y: WMD: 0.015% h-1, 95% CI: [0.007, 0.022] % h-1, I2 = 76%, k = 12, P = 0.002) compared to younger adults (<35 y: WMD: 0.041% h-1, 95% CI: [0.030, 0.052] % h-1, I2 = 88%, k = 25, P < 0.001). Individual studies have reported that the temporal proximity of the RE, muscle group, muscle protein fraction, RE training experience, and the loading parameters of the RE (i.e., intensity, workload, and effort) appeared to affect the MPS response to RE, whereas sex or type of muscle contraction does not. A single bout of RE can sustain measurable increases in postabsorptive MPS soon after RE cessation and up to 48 h post-RE. However, there is substantial heterogeneity in the magnitude and time course of the MPS response between trials, which appears to be influenced by participants' age and/or the loading parameters of the RE itself.

High-protein diet with excess leucine prevents inactivity-induced insulin resistance in women

Background and aimsMuscle inactivity leads to muscle atrophy and insulin resistance. The branched-chain amino acid (BCAA) leucine interacts with the insulin signaling pathway to modulate glucose metabolism. We have tested the ability of a high-protein BCAA-enriched diet to prevent insulin resistance during long-term bed rest (BR). MethodsStable isotopes were infused to determine glucose and protein kinetics in the postabsorptive state and during a hyperinsulinemic-euglycemic clamp in combination with amino acid infusion (Clamp+AA) before and at the end of 60 days of BR in two groups of healthy, young women receiving eucaloric diets containing 1 g of protein/kg per day (n=8) or 1.45 g of protein/kg per day enriched with 0.15 g/kg per day of BCAAs (leucine/valine/isoleucine=2/1/1) (n=8). Body composition was determined by Dual X-ray Absorptiometry. ResultsBR decreased lean body mass by 7.6±0.3% and 7.2±0.8% in the groups receiving conventional or high protein-BCAA diets, respectively. Fat mass was unchanged in both groups.At the end of BR, percent changes of insulin-mediated glucose uptake significantly (p=0.01) decreased in the conventional diet group from 155±23% to 84±10% while did not change significantly in the high protein-BCAA diet group from 126±20% to 141±27% (BR effect, p=0.32; BR/diet interaction, p=0.01; Repeated Measures ANCOVA). In contrast, there were no BR/diet interactions on proteolysis and protein synthesis Clamp+AA changes in the conventional diet and the high protein-BCAA diet groups. ConclusionA high protein-BCAA enriched diet prevented inactivity-induced insulin resistance in healthy women.

THU390 Case Report On Hirata Syndrome: A Rare Cause Of Hypoglycemia

Abstract Disclosure: M. Pranala: None. V. Kuttiyil Oommen: None. V. Sanker: None. S. Vallabhaneni: None. K. Ajith: None. A. Thomas: None. Introduction: Hirata's disease, also known as insulin autoimmune syndrome (IAS), is a rare cause of hypoglycemia that is characterized by episodes of spontaneous hypoglycemia and insulin autoantibodies in patients who have not received exogenous insulin. IAS has been associated with rheumatoid arthritis and Graves' disease in 96% of Japanese IAS patients, and it has also been associated with other autoimmune disorders like Graves' disease. Case History: We report a case of 73-year-old male presented with the complaints of episodes of profuse sweating, palpitation and numbness over his head. Patient was initially treated symptomatically and since the symptoms were not resolving further evaluation was done. Two hourly GRBS, c- peptide, insulin levels and serum cortisol of our patient was monitored. Patient had extremely high serum insulin levels. Serum insulin antibodies level was also high (&amp;gt;300 U/ml). CT abdomen ruled out pancreatic pathology. It has been speculated that hypoglycemia occurring in IAS is due to dissociation of insulin from its antibodies in the post absorptive state. Our patient was diagnosed with IAS based on the criteria of Hirata. The age at onset, sex, and duration of hypoglycemic attacks, outcome or treatment, medication taken prior to the onset of IAS and background disease were all taken into consideration. In our patient, hypoglycemia occurred spontaneously in the post-absorptive state 4–6 hours after meal rather than after a 72-hour fast test. Extremely high levels of insulin (&amp;gt;200 µIU/mL) and Serum insulin antibodies found to be &amp;gt;30 U/ml were constructive in the diagnosis of IAS. The patient improved on dietary management alone consisting of frequent small meals. Conclusion: In order to facilitate early recognition and prevent unnecessary investigations, this could be the most significant syndrome in the differential diagnosis of endogenous hyper-insulinemic hypoglycemia (EHH). In such patients with a high index of suspicion, insulin autoantibodies should be examined. IAA prevents insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia Presentation: Thursday, June 15, 2023

Sex related differences in muscle health and metabolism in chronic obstructive pulmonary disease

Sex differences in muscle function and mass, dyspnea, and clinical outcomes have been observed in patients with Chronic Obstructive Pulmonary Disease (COPD) despite a similar level of airflow obstruction. Protein and amino acid metabolism is altered in COPD, however, it remains unclear whether a difference in metabolic signature exists between males and females with COPD that may explain the observed differences in muscle health and clinical outcomes. In 234 moderate to severe COPD patients (males/females: 113/121) and 182 healthy controls (males/females: 77/105), we assessed, besides presence of comorbidities and clinical features, muscle function by handgrip and leg dynamometry, and body composition by dual-energy x-ray absorptiometry. In the postabsorptive state, a mixture of 18 stable isotopes of amino acids was administered by pulse and arterialized blood was sampled for 2h. Amino acid concentrations and enrichments were analyzed by LC-MS/MS to calculate whole body (net) protein breakdown (WBnetPB) and whole body production (WBP) rates (μmol/hour) of the amino acids playing a known role in muscle health. Statistics was done by ANCOVA to examine the effects of sex, COPD, and sex-by-COPD interaction with as covariates age and lean mass. Significance was set as p<0.05. Lung function was comparable between males and females with COPD. Being a female and presence of COPD were independently associated with lower appendicular lean mass, muscle strength, and WBnetPB (p<0.05). Being a male was associated with higher visceral adipose tissue, C-reactive protein (CRP) (p<0.05), and higher prevalence of heart failure and obstructive sleep apnea. Sex-by-COPD interactions were found indicating lower fat mass (p=0.0005) and WBPs of phenylalanine (measure of whole body protein turnover) and essential amino acids (p<0.05), particularly in COPD females. Higher visceral adipose tissue (p=0.025), CRP (p<0.0001), and WBP of tau-methylhistidine (p=0.010) (reflecting enhanced myofibrillar protein breakdown) were observed in COPD males. Presence of sex specific changes in protein and amino acid metabolism and cardiometabolic health in COPD need to be considered when designing treatment regimens to restore muscle health in males and females with COPD. www. gov, NCT01787682, NCT01624792, NCT02157844, NCT02065141, NCT02770092, NCT02780219, NCT03327181, NCT03796455, NCT01173354, NCT01154400.

An evaluation of basal metabolic rate among healthy individuals — a cross-sectional study

BackgroundThe main source of daily energy requirement in Asian societies is basal metabolic rate (BMR). Even though the reason for this fluctuation is debatable, prior research have shown that BMR is highly varied in individuals. All studies concur that variation in fat-free mass (FFM) is important, although the effects of fat mass (FM), age, sex, and the hormones leptin, triiodothyronine (T3), and thyroxine (T4) are still unknown.ObjectiveThe main objectives of the study are as follows:• To evaluate the basal metabolic rate among healthy individuals• To identify the risk factors on basal metabolic rate among healthy individualsMethodologyIn total, 50 individuals were consecutively enrolled in the study during the entrepreneurship studio on 29th June 2022 held at Garden City University (GCU). The inclusion criteria were age between 18 and 50 years, both males and females, students and professors of GCU, and healthy individuals. The exclusion criteria were subjects who had overt metabolic and/or endocrine diseases (e.g., diabetes, hypothyroidism, hypertension, amenorrhea) and those taking any drug known to influence energy metabolism. The convenient samples of 50 subjects were taken from this study.Outcome measuresBasal metabolic rate (BMR) and body mass index (BMI).ResultsThe demographic data, height, weight, BMI, and BMR were recorded. The mean and standard deviation of age are 25.81 ± 8.71 and 23.95 ± 6.67 of males and females, respectively. The mean and standard deviation of height are 1.68 ± 0.68 and 1.63 ± 0.07, respectively. The mean and standard deviation for weight are 63.8 ± 11.49 and 54.86 ± 10.43, respectively. The mean and standard deviation of BMI are males and females which are 22.3 ± 3.22 and 20.47 ± 3.62, respectively. The mean and standard deviation of BMR are males and females which are 1552.41 ± 127.3 and 1327.7 ± 147.9.ConclusionThe energy used up while lying still at rest and being awake during the nocturnal postabsorptive state is known as the basal metabolic rate (BMR). The values can be used as a reference for comparison with the normative values, and cardiorespiratory endurance training can be included in the rehabilitation program.

Short-term disuse does not affect postabsorptive or postprandial muscle protein fractional breakdown rates.

The decline in postabsorptive and postprandial muscle protein fractional synthesis rates (FSR) does not quantitatively account for muscle atrophy during uncomplicated, short-term disuse, when atrophy rates are the highest. We sought to determine whether 2days of unilateral knee immobilization affects mixed muscle protein fractional breakdown rates (FBR) during postabsorptive and simulated postprandial conditions. Twenty-three healthy, male participants (age: 22±1year; height: 179±1cm; body mass: 73.4±1.5kg; body mass index 22.8±0.5kg·m-2 ) took part in this randomized, controlled study. After 48h of unilateral knee immobilization, primed continuous intravenous l-[15 N]-phenylalanine and l-[ring-2 H5 ]-phenylalanine infusions were used for parallel determinations of FBR and FSR, respectively, in a postabsorptive (saline infusion; FAST) or simulated postprandial state (67.5mg·kg body mass-1 ·h-1 amino acid infusion; FED). Bilateral m. vastus lateralis biopsies from the control (CON) and immobilized (IMM) legs, and arterialized-venous blood samples, were collected throughout. Amino acid infusion rapidly increased plasma phenylalanine (59±9%), leucine (76±5%), isoleucine (109±7%) and valine (42±4%) concentrations in FED only (all P<0.001), which was sustained for the remainder of infusion. Serum insulin concentrations peaked at 21.8±2.2mU·L-1 at 15min in FED only (P<0.001) and were 60% greater in FED than FAST (P<0.01). Immobilization did not influence FBR in either FAST (CON: 0.150±0.018; IMM: 0.143±0.017%·h-1 ) or FED (CON: 0.134±0.012; IMM: 0.160±0.018%·h-1 ; all effects P>0.05). However, immobilization decreased FSR (P<0.05) in both FAST (0.071±0.004 vs. 0.086±0.007%·h-1 ; IMM vs CON, respectively) and FED (0.066±0.016 vs. 0.119±0.016%·h-1 ; IMM vs CON, respectively). Consequently, immobilization decreased net muscle protein balance (P<0.05) and to a greater extent in FED (CON: -0.012±0.025; IMM: -0.095±0.023%·h-1 ; P<0.05) than FAST (CON: -0.064±0.020; IMM: -0.072±0.017%·h-1 ). We conclude that merely 2days of leg immobilization does not modulate postabsorptive and simulated postprandial muscle protein breakdown rates. Instead, under these conditions the muscle negative muscle protein balance associated with brief periods of experimental disuse is driven near exclusively by reduced basal muscle protein synthesis rates and anabolic resistance to amino acid administration.

Predicting resting energy expenditure: a critical appraisal.

The most commonly used prediction models for resting energy expenditure (REE) are Harris-Benedict (1919), Schofield (1985), Owen (1986), and Mifflin-St Jeor (1990), based on height, weight, age and gender, and Cunningham (1991), based on body composition. Here, the five models are compared with reference data, consisting of individual REE measurements (n = 353) from 14 studies, covering a large range of participant characteristics. For white adults, prediction of REE with the Harris-Benedict model approached measured REE most closely, with estimates within 10% for more than 70% of the reference population. Sources of differences between measured and predicted REE include measurement validity and measurement conditions. Importantly, a 12- to 14-h overnight fast may not be sufficient to reach post-absorptive conditions and may explain differences between predicted REE and measured REE. In both cases complete fasting REE may not have been achieved, especially in participants with high energy intake. In white adults, measured resting energy expenditure was closest to predicted values with the classic Harris-Benedict model. Suggestions for improving resting energy expenditure measurements, as well as prediction models, include the definition of post-absorptive conditions, representing complete fasting conditions with respiratory exchange ratio as indicator.

Postabsorptive muscle protein synthesis is higher in outpatients as compared to inpatients.

Several factors affect muscle protein synthesis (MPS) in the postabsorptive state. Extreme physical inactivity (e.g., bedrest) may reduce basal MPS, whereas walking may augment basal MPS. We hypothesized that outpatients would have a higher postabsorptive MPS than inpatients. To test this hypothesis, we conducted a retrospective analysis. We compared 152 outpatient participants who arrived at the research site the morning of the MPS assessment with 350 Inpatient participants who had an overnight stay in the hospital unit before the MPS assessment the following morning. We used stable isotopic methods and collected vastus lateralis biopsies ∼2 to 3 h apart to assess mixed MPS. MPS was ∼12% higher (P < 0.05) for outpatients than inpatients. Within a subset of participants, we discovered that after instruction to limit activity, outpatients (n = 13) took 800 to 900 steps in the morning to arrive at the unit, seven times more steps than inpatients (n = 12). We concluded that an overnight stay in the hospital as an inpatient is characterized by reduced morning activity and causes a slight but significant reduction in MPS compared with participants studied as outpatients. Researchers should be aware of physical activity status when designing and interpreting MPS results.NEW & NOTEWORTHY The postabsorptive muscle protein synthesis rate is lower in the morning after an overnight inpatient hospital stay compared with an outpatient visit. Although only a minimal amount of steps was conducted by outpatients (∼900), this was enough to increase postabsorptive muscle protein synthesis rate.

Improved glycemic control either alone, or combined with antioxidant supplementation, fails to restore blood glutathione or markers of oxidative stress in adolescents with poorly controlled type 1 diabetes

In earlier studies, we showed that adolescents with type 1 diabetes mellitus (T1DM) have significant glutathione (GSH) depletion and that GSH is reciprocally related to glycemic control. In both the general population and in those with diabetes, the use of over-the-counter antioxidant supplements is widespread. We hypothesized that improved glycemic control, alone or in combination with dietary antioxidants, would restore blood GSH pool. The study included 41 participants who were 15.8 ± 2.4 years of age (mean ± standard deviation) and with poorly controlled T1DM (hemoglobin A1c [HbA1c] 8.2 ± 0.6%). Erythrocyte GSH, and 3-nitrotyrosine, F2-isoprostane, and 8-hydroxy-2′-deoxy-guanosine (as markers of protein, lipid, and DNA oxidative stress, respectively) were determined in the postabsorptive state after blood glucose was maintained overnight near euglycemia. Participants were then randomized to a mix of antioxidants (vitamin C, selenium, zinc, vitamin E, β-carotene) or placebo for 3 to 6 months, and diabetes management was intensified using CSII (n = 30) or multiple daily injections (n = 11) coupled with CDE phone calls and visits with a Nutritionist. A second, identical study was performed when/if a drop in HbA1c ≥0.5% was achieved. HbA1c levels dropped similarly in both groups (from 8.9 ± 1.0% to 7.9 ± 0.9% and 8.5 ± 0.6% to 7.7 ± 0.7% in placebo and antioxidant group, respectively). Neither total nor reduced GSH was altered by improved metabolic control. Markers of protein, lipid, and DNA oxidation remained unaltered. We conclude that, in youngsters with T1DM, neither a significant improvement in diabetes control over a 3-month period nor the regimen of dietary antioxidant supplied in the current study can mitigate oxidative stress. These findings suggest that, in adolescents with T1DM, (1) more sustained improvement of diabetes control may be needed to alleviate oxidative stress and (2) the putative benefit of antioxidant supplements remains to be proven.

Direct and systemic actions of growth hormone receptor (GHR)-signaling on hepatic glycolysis, de novo lipogenesis and insulin sensitivity, associated with steatosis

BackgroundEvidence is accumulating that growth hormone (GH) protects against the development of steatosis and progression of non-alcoholic fatty liver disease (NAFLD). GH may control steatosis indirectly by altering systemic insulin sensitivity and substrate delivery to the liver and/or by the direct actions of GH on hepatocyte function. ApproachTo better define the hepatocyte-specific role of GH receptor (GHR) signaling on regulating steatosis, we used a mouse model with adult-onset, hepatocyte-specific GHR knockdown (aHepGHRkd). To prevent the reduction in circulating insulin-like growth factor 1 (IGF1) and the subsequent increase in GH observed after aHepGHRkd, subsets of aHepGHRkd mice were treated with adeno-associated viral vectors (AAV) driving hepatocyte-specific expression of IGF1 or a constitutively active form of STAT5b (STAT5bCA). The impact of hepatocyte-specific modulation of GHR, IGF1 and STAT5b on carbohydrate and lipid metabolism was studied across multiple nutritional states and in the context of hyperinsulinemic:euglycemic clamps. ResultsChow-fed male aHepGHRkd mice developed steatosis associated with an increase in hepatic glucokinase (GCK) and ketohexokinase (KHK) expression and de novo lipogenesis (DNL) rate, in the post-absorptive state and in response to refeeding after an overnight fast. The aHepGHRkd-associated increase in hepatic KHK, but not GCK and steatosis, was dependent on hepatocyte expression of carbohydrate response element binding protein (ChREBP), in re-fed mice. Interestingly, under clamp conditions, aHepGHRkd also increased the rate of DNL and expression of GCK and KHK, but impaired insulin-mediated suppression of hepatic glucose production, without altering plasma NEFA levels. These effects were normalized with AAV-mediated hepatocyte expression of IGF1 or STAT5bCA. Comparison of the impact of AAV-mediated hepatocyte IGF1 versus STAT5bCA in aHepGHRkd mice across multiple nutritional states, indicated the restorative actions of IGF1 are indirect, by improving systemic insulin sensitivity, independent of changes in the liver transcriptome. In contrast, the actions of STAT5b are due to the combined effects of raising IGF1 and direct alterations in the hepatocyte gene program that may involve suppression of BCL6 and FOXO1 activity. However, the direct and IGF1-dependent actions of STAT5b cannot fully account for enhanced GCK activity and lipogenic gene expression observed after aHepGHRkd, suggesting other GHR-mediated signals are involved. ConclusionThese studies demonstrate hepatocyte GHR-signaling controls hepatic glycolysis, DNL, steatosis and hepatic insulin sensitivity indirectly (via IGF1) and directly (via STAT5b). The relative contribution of these indirect and direct actions of GH on hepatocytes is modified by insulin and nutrient availability. These results improve our understanding of the physiologic actions of GH on regulating adult metabolism to protect against NAFLD progression.

Influence of Fasting until Noon (Extended Postabsorptive State) on Clock Gene mRNA Expression and Regulation of Body Weight and Glucose Metabolism.

The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an "extended postabsorptive state", has the potential to cause a deleterious effect on clock gene expression and to disrupt regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, and appetite, and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases and the consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantages of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.