Fof Several insluin and rodent studies suggest Body fat estimation in addition sensitiivty the amount Body fat estimation energy consumed, insuulin of food intake timibg to jnsulin weight HbAc significance.
Consuming most energy Nutrieng the morning has favorable effects on weight loss Nugrient weight maintenance.
Whether this also affects Nutrienr metabolism and sensitovity fat independently from weight loss is unknown. Objective: HbAc significance hypothesized that during weight insukin, consuming most Nutrient timing for insulin sensitivity in HbAc significance sensitiviy improves insulin sensitivity and reduces Hydration and recovery in young athletes fat content more Prescription water weight reduction consuming most energy in the evening.
Methods: Twenty-three obese insulin resistant men age Insulin sensitivity, measured with a two-step hyperinsulinemic euglycemic clamp using a glucose tracer, intrahepatic triglycerides IHTGmeasured using magnetic resonance spectroscopy, and resting energy expenditure REE were assessed before and after the diet intervention.
Results: Meal macronutrient composition and weight loss 6. In addition, both groups decreased REE and respiratory quotient equally. Conclusions: During weight loss, consuming most energy in the morning instead of the evening does not have additional beneficial effects on insulin sensitivity and IHTG content.
These results do not support weight independent effects of meal timing on glucose metabolism and IHTG in hypocaloric conditions in obese men. Abstract Background: Several human and rodent studies suggest that in addition to the amount of energy consumed, timing of food intake contributes to body weight regulation.
Publication types Randomized Controlled Trial Research Support, Non-U. Substances Blood Glucose Triglycerides.
: Nutrient timing for insulin sensitivity| Meal Timing and Insulin | snack to 1½ Tbsp. Jarrett RJ, Baker IA, Keen H, Oakley NW. Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent type II diabetes mellitus. J Clin Invest. Calculation of substrate oxidation rates in vivo from gaseous exchange. Remaining muscle for glycogen and gene expression analysis was frozen in liquid nitrogen and stored at —80°C. |
| Second Meal Effect | In general, for outcomes such as energy expenditure [2] , weight or fat loss [3] , blood lipids and blood pressure [4] , there is little difference in various meal timing regimens. Alan is currently pursuing his PhD in nutrition at the University of Surrey, UK, with a research focus in chrononutrition. BMC Public Health 18 , Demographic, lifestyle characteristics, and health status of the study participants were compared between either sex by using χ 2 for categorical variables and a t-test for continuous variables. Waist-hip ratio WHR was calculated for each person by dividing WC by hip circumference. Am J Clin Nutr ; 88 : — Image origally from: Circadian Eating Lecture - Danny Lennon In the Bath Breakfast Project [32] , participants were randomised to either consume more than kcal before 11 a. |
| We Care About Your Privacy | Project : Research council. Gonzalez, J. The Physiological Society. Project : UK charity. Rank Prize Fund. Edinburgh, R. Creator , Bradley, H. Creator , Abdullah, N. Creator , Robinson, S. Creator , Chrzanowski-Smith, O. Creator , Walhin, J. Creator , Joanisse, S. Creator , Manolopoulos, K. Creator , Philp, A. Creator , Hengist, A. Creator , Chabowski, A. Creator , Brodsky, F. Creator , Koumanov, F. Creator , Betts, J. Creator , Thompson, D. Creator , Wallis, G. Creator , University of Bath, 19 Oct DOI : Breakfast: Much like snacks, Fung contends that breakfast foods are unhealthy and contribute to obesity. Research shows that breakfast is inessential to good health, and Fung recommends skipping it or replacing carb- and sugar-heavy breakfast foods with whole, unprocessed foods such as salmon or a salad. Shortform note: In addition to marketing breakfast as essential, which Fung notes, the creators of breakfast cereals used religious moralizing to push their wheat-based cereals. Further, cereal became known as a reliable kickstart to the workday, such that people associated breakfast with increased productivity, another nearly moral imperative to American society. Here's what you'll find in our full The Obesity Code summary :. Growing up, however, she found herself transitioning to non-fiction, psychological, and self-help books. She has a degree in Psychology and a deep passion for the subject. Some of her favorites include Thinking, Fast and Slow, How We Decide, and The Wisdom of the Enneagram. Your email address will not be published. Save my name, email, and website in this browser for the next time I comment. Skip to content. Posted by Darya Sinusoid Jul 28, Association of rotating night shift work with BMI and abdominal obesity among nurses and midwives. PLoS One ; 10 : e Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med ; : — Rosenbaum M, Hirsch J, Gallagher DA, Leibel RL. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr ; 88 : — Sumithran P, Proietto J. The defence of body weight: a physiological basis for weight regain after weight loss. Keim NL, Van Loan MD, Horn WF, Barbieri TF, Mayclin PL. Weight loss is greater with consumption of large morning meals and fat-free mass is preserved with large evening meals in women on a controlled weight reduction regimen. J Nutr ; : 75— Consoli A, Capani F, Del Ponte A, Guagnano T, Iezzi M, Ditano G et al. Boll Soc Ital Biol Sper ; 57 : — Bradley U, Spence M, Courtney CH, McKinley MC, Ennis CN, McCance DR et al. Low-fat versus low-carbohydrate weight reduction diets effects on weight loss, insulin resistance, and cardiovascular risk: a randomized control trial. Diabetes ; 58 : — Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology ; : — Thomas EL, Brynes AE, Hamilton G, Patel N, Spong A, Goldin RD et al. Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease. World J Gastroenterol ; 12 : — Korenblat KM, Fabbrini E, Mohammed BS, Klein S. Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects. Visser ME, Lammers NM, Nederveen AJ, van der Graaf M, Heerschap A, Ackermans MT et al. Hepatic steatosis does not cause insulin resistance in people with familial hypobetalipoproteinaemia. Diabetologia ; 54 : — Download references. We acknowledge our research assistant Martine van Vessem for help with the clamps. This research was supported by the Dutch Technology Foundation STW Perspective grant OnTime project , which is part of the Netherlands Organization for Scientific Research NWO , and which is partly funded by the Ministry of Economic Affairs. RV, MS and SF designed research; RV conducted the research; RV, AN and MT analyzed the data; RV wrote the paper; and SF and MS had primary responsibility for the final content. All authors read and approved the final manuscript. Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. You can also search for this author in PubMed Google Scholar. Correspondence to M J Serlie or S E la Fleur. MS serves on the advisory board of Fresenius Kabi Netherlands Zeist, The Netherlands. The remaining authors declare no conflict of interest. Reprints and permissions. Versteeg, R. et al. Meal timing effects on insulin sensitivity and intrahepatic triglycerides during weight loss. Int J Obes 42 , — Download citation. Received : 11 November Revised : 09 May Accepted : 05 July Published : 16 August Issue Date : February Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content Thank you for visiting nature. nature international journal of obesity original article article. Subjects Energy metabolism Insulin signalling Nutrition Obesity Type 2 diabetes Weight management. Abstract Background: Several human and rodent studies suggest that in addition to the amount of energy consumed, timing of food intake contributes to body weight regulation. Objective: We hypothesized that during weight loss, consuming most energy in the morning improves insulin sensitivity and reduces hepatic fat content more than consuming most energy in the evening. Methods: Twenty-three obese insulin resistant men age Results: Meal macronutrient composition and weight loss 6. Conclusions: During weight loss, consuming most energy in the morning instead of the evening does not have additional beneficial effects on insulin sensitivity and IHTG content. Access through your institution. Buy or subscribe. Change institution. Learn more. Figure 1. Figure 2. Figure 3. References Flegal KM, Carroll MD, Ogden CL, Johnson CL. Article Google Scholar Schmidt M, Johannesdottir SA, Lemeshow S, Lash TL, Ulrichsen SP, Botker HE et al. Article Google Scholar Ruhl CE, Everhart JE. Article CAS Google Scholar Garaulet M, Gomez-Abellan P. Article CAS Google Scholar Viljanen AP, Iozzo P, Borra R, Kankaanpaa M, Karmi A, Lautamaki R et al. Article CAS Google Scholar Niskanen L, Uusitupa M, Sarlund H, Siitonen O, Paljarvi L, Laakso M. CAS PubMed Google Scholar Wing RR, Phelan S. Article Google Scholar Koopman KE, Caan MW, Nederveen AJ, Pels A, Ackermans MT, Fliers E et al. Article CAS Google Scholar Baron KG, Reid KJ, Kern AS, Zee PC. Article Google Scholar Wang JB, Patterson RE, Ang A, Emond JA, Shetty N, Arab L. Article Google Scholar Garaulet M, Gomez-Abellan P, Alburquerque-Bejar JJ, Lee YC, Ordovas JM, Scheer FA. Article CAS Google Scholar Jakubowicz D, Barnea M, Wainstein J, Froy O. Article CAS Google Scholar Jakubowicz D, Froy O, Wainstein J, Boaz M. Article CAS Google Scholar Jarrett RJ, Baker IA, Keen H, Oakley NW. Article CAS Google Scholar Lee A, Ader M, Bray GA, Bergman RN. |
| How Meal Timing Affects Your Insulin Levels | Shortform Books | A major factor that contributes to chronically high insulin levels is meal timing. Constant insulin release occurs when we eat too frequently. Insulin levels increase in response to food, and they decrease between periods of eating. If you leave little or no time between periods of eating, you never allow your insulin to return to normal levels. Shortform note: Additional risk factors for insulin resistance include smoking and drinking alcohol in excess. Chronic cigarette smokers appear to have a higher insulin response and take longer to clear insulin away , while a rat-based study found that binge drinking as often as one time monthly decreased insulin sensitivity. This effect persisted for 54 hours, and the researchers speculate that this is due to impaired function of the hypothalamus, which communicates with insulin to coordinate insulin sensitivity and set weight. In addition, eating constantly keeps your glucose and glycogen stores full, preventing you from burning your fat stores as fuel. Fung explains that neither snacking nor breakfast are strictly necessary. Snacking: According to Fung, snacks have little or no nutritional value and no place in a healthy diet. Snacks are often made of refined carbohydrates, such as wheat and sugar, so they spike your insulin levels and contribute to obesity. Legacy companies still hold a large share of the market, but consumers increasingly want healthier options and more diverse flavors. Breakfast: Much like snacks, Fung contends that breakfast foods are unhealthy and contribute to obesity. Research shows that breakfast is inessential to good health, and Fung recommends skipping it or replacing carb- and sugar-heavy breakfast foods with whole, unprocessed foods such as salmon or a salad. Shortform note: In addition to marketing breakfast as essential, which Fung notes, the creators of breakfast cereals used religious moralizing to push their wheat-based cereals. Further, cereal became known as a reliable kickstart to the workday, such that people associated breakfast with increased productivity, another nearly moral imperative to American society. Here's what you'll find in our full The Obesity Code summary :. Growing up, however, she found herself transitioning to non-fiction, psychological, and self-help books. By becoming the opposite—more insulin sensitive—the muscle, fat and liver cells need less insulin to absorb the glucose. In addition to changing your diet, physical activity, weight loss, stress reduction and proper sleep can all make you more sensitive to insulin. There are a few key changes that can help improve your blood sugar and, therefore, improve insulin resistance:. Daily Totals: 1, calories, g protein, g carbohydrates, 18 g fiber, 70 g fat, 1, mg sodium. To make it 1, calories: Omit the almonds at P. snack and omit the salad with vinaigrette at dinner. To make it 2, calories: Increase to ½ cup almonds at breakfast, add ¼ cup unsalted dry-roasted peanuts to A. Daily Totals: 1, calories, 92 g protein, g carbohydrate, 20 g fiber, 66 g fat, 1, mg sodium. To make it 1, calories: Omit the blueberries at breakfast and change the A. snack to 1 clementine. To make it 2, calories: Increase the blueberries at breakfast to 1 cup, change the banana at A. snack to large and the peanut butter to 3 Tbsp. Daily Totals : 1,calories, 92 g protein, g carbohydrates, 28 g fiber, 68 g fat, 2, mg sodium. To make it 1, calories: Omit the pear at breakfast and reduce to ¼ cup yogurt at A. To make it 2, calories: Increase to 1 cup yogurt and 3 Tbsp. almonds at A. snack, and add 1 Tbsp. peanut butter to P. Daily Totals : 1, calories, 74 g protein, g carbohydrates, 30 g fiber, 88 g fat, 1, mg sodium. To make it 1, calories: Omit clementines at breakfast and apple at lunch. Reduce to 2 Tbsp. almonds at P. To make it 2, calories: Increase to 7 Tbsp. chopped walnuts at A. snack; increase to 6 Tbsp. Daily Totals: 1, calories, 73 g protein, g carbohydrates, 41 g fiber, 84 g fat, 1, mg sodium. To make it 1, calories: Reduce almonds at A. snack to 1½ Tbsp. snack to 1 Tbsp. To make it 2, calories: Add 2 hard-boiled eggs to breakfast and add 1 medium banana and 2½ Tbsp. peanut butter to lunch. Daily Totals: 1, calories, 78 g protein, g carbohydrates, 32 g fiber, 73 g fat, 1, mg sodium. To make it 1, calories: Swap the cashews in the A. snack for 1 mozzarella string cheese and omit the P. To make it 2, calories: Add 2 hard-boiled eggs to breakfast, increase the cashews at A. snack to 9 Tbsp. Daily Totals: 1, calories, g protein, g carbohydrates, 35 g fiber, 63 g fat, 1, mg sodium. snack, and omit avocado at dinner. To make it 2, calories: Increase to ½ cup walnuts at breakfast, increase to 2 string cheese at A. snack, and increase to 1 avocado at dinner. Use limited data to select advertising. |
Nutrient timing for insulin sensitivity -
almonds at P. To make it 2, calories: Increase to 7 Tbsp. chopped walnuts at A. snack; increase to 6 Tbsp.
Daily Totals: 1, calories, 73 g protein, g carbohydrates, 41 g fiber, 84 g fat, 1, mg sodium. To make it 1, calories: Reduce almonds at A. snack to 1½ Tbsp. snack to 1 Tbsp. To make it 2, calories: Add 2 hard-boiled eggs to breakfast and add 1 medium banana and 2½ Tbsp.
peanut butter to lunch. Daily Totals: 1, calories, 78 g protein, g carbohydrates, 32 g fiber, 73 g fat, 1, mg sodium.
To make it 1, calories: Swap the cashews in the A. snack for 1 mozzarella string cheese and omit the P. To make it 2, calories: Add 2 hard-boiled eggs to breakfast, increase the cashews at A. snack to 9 Tbsp.
Daily Totals: 1, calories, g protein, g carbohydrates, 35 g fiber, 63 g fat, 1, mg sodium. snack, and omit avocado at dinner. To make it 2, calories: Increase to ½ cup walnuts at breakfast, increase to 2 string cheese at A.
snack, and increase to 1 avocado at dinner. Use limited data to select advertising. Create profiles for personalised advertising. Use profiles to select personalised advertising.
Create profiles to personalise content. Use profiles to select personalised content. Measure advertising performance. Measure content performance.
Understand audiences through statistics or combinations of data from different sources. This project comprised 2 experiments. We first assessed the acute metabolic and mRNA responses to manipulating nutrient-exercise timing Acute Study , followed by a 6-week randomized, controlled trial to assess the longer-term adaptations in response to carbohydrate-exercise timing Training Study.
All participants provided informed written consent prior to participation. Potential participants were excluded if they had any condition or were taking any medication known to alter any of the outcome measures. gov NCT and NCT, respectively.
In the Acute Study, 12 sedentary men classified as overweight or obese were recruited from the Birmingham region of the United Kingdom.
The main exclusion criteria included being regularly physically active, having hypertension, or having possible undiagnosed T2D.
Participant characteristics are shown in Table 1. Data are means standard deviation for men classified as overweight or obese.
Abbreviations: BMI, body mass index; V̇O 2 peak, peak oxygen uptake; PPO, peak power output; CON, control; CHO-EX, carbohydrate-exercise; EX-CHO, exercise-carbohydrate. This was a randomized crossover study where on 1 visit breakfast-exercise , a standardized breakfast cornflake cereal with skimmed milk, whole meal toast, sunflower spread, and strawberry jam was consumed upon arrival at the laboratory and following 48 hours of diet control.
Expired gas samples were collected at 25 to 30 minutes and 55 to 60 minutes of exercise to determine whole-body substrate utilization rates. Blood was sampled in the overnight-fasted state, at 45 minutes post breakfast and immediately before exercise was performed 90 minutes post breakfast , every 30 minutes during exercise and at minute intervals during a 3-hour postexercise recovery.
On the other visit exercise-breakfast , the participants completed the same protocol, but the breakfast was consumed immediately after the postexercise muscle sample. The primary outcome for the Acute Study was intramuscular lipid utilization during exercise before versus after nutrient ingestion.
To assess longer-term adaptive ie, training responses to altering nutrient- carbohydrate- exercise timing Training Study , we recruited 30 sedentary men who were overweight and obese self-reported nonexercisers from the Bath region of the United Kingdom Table 1.
The duration of the exercise sessions progressed from 30 week 1 to 40 week 2 to 50 minutes weeks 3—6. All sessions were supervised at the University of Bath. During every one of the exercise training sessions, 1-minute expired gas samples were collected every 10 minutes to assess substrate utilization and heart rate Polar Electro Oy, Kempele, Finland , and ratings of perceived exertion 31 were recorded.
Participants ate their evening meal before hours the evening prior to any exercise sessions. Participants in CHO-EX were given a drink in an opaque bottle made from 1.
They were asked not to eat or drink anything else except water ad libitum in this period and confirmed they had consumed the drink before exercising. After exercise, they were provided a taste-matched placebo water and vanilla flavoring to consume 2 hours after exercise and were asked not to consume anything else during this period.
Participants in EX-CHO were given the same drinks but with the order of the drinks reversed. Participants in CON were given the same drinks for 3 days per week during the intervention, with the carbohydrate drink as breakfast — hours and the placebo for consumption with their lunch — hours.
These participants were asked not to consume anything else between the drinks. There were no other diet controls in the intervention. Pre- and postintervention, an oral glucose tolerance test OGTT , a vastus lateralis sample fasting, rested state , and an exercise test to assess V̇O 2 peak and the capacity for lipid utilization during exercise in the fasted state were undertaken.
Postintervention tests were between 24 hours and 48 hours for muscle sampling and between 48 hours and 72 hours for OGTT after the last exercise training session to reduce any residual effects of the last exercise bout performed on these measurements.
The primary outcome for the Training Study was the pre- to postintervention change in the glycemic and insulinemic responses to the OGTT, which were also used to derive an index of OGIS as described subsequently.
For both studies, the participants were asked to maintain their normal physical activity behaviors and to abstain from alcoholic and caffeinated drinks for 24 hours prior to all main laboratory trials. Food intake ceased at a mean [range] of hours [ hours] on the evening before testing, and participants fasted overnight minimum of 10 hours.
For all trials, participants arrived at the laboratory at a mean [range] of hours [ hours], with the exact time replicated for subsequent trials. For the Training Study, they recorded the composition of their evening meal on the day before in a preintervention trial and replicated this meal for the postintervention trial, in line with guidelines for testing postprandial glycemic control This protocol produces fasting muscle and liver glycogen and fasting intramuscular lipid concentrations that are consistent across trial days Stature was measured to the nearest 0.
Body mass was measured to the nearest 0. Waist and hip circumferences were measured to the nearest 0. Participants completed exercise tests on an electronically braked ergometer. In the Acute Study, the starting intensity was 35 Watts W , and this was increased by 35 W every 3 minutes until volitional exhaustion.
In the Training Study, the starting intensity for the exercise test was 50 W, which was increased by 25 W every 3 minutes. Heart rate Polar Electro Oy, Kempele, Finland and continuous breath-by-breath measurements were recorded Acute Study: Oxycon Pro, Jaeger, Wurzburg, Germany; Training Study: TrueOne, ParvoMedics, Sandy, USA.
Volume and gas analyzers were calibrated using a 3-L calibration syringe Hans Rudolph, Kansas City, USA and a calibration gas PPO was calculated as the work rate of the final completed stage plus the fraction of time in the final, noncompleted stage, multiplied by the W increment. V̇O 2 peak was the highest measured V̇O 2 over a second period, using methods and attainment criteria previously reported In the Acute Study, 10 mL of blood was sampled from an antecubital forearm vein and 6 mL dispensed into ethylenediaminetetraacetic acid-coated tubes BD, Oxford, UK and centrifuged 4°C at rpm for 15 minutes Heraeus Biofuge Primo R, Kendro Laboratory Products Plc.
Resultant plasma was dispensed into 0. A proportion of the sample 4 mL was allowed to clot for serum in a plain vacutainer prior to centrifugation. Samples were analyzed for plasma glucose, glycerol, and non-esterified fatty acid NEFA using an ILAB Clinical Chemistry Analyzer Instrumentation Laboratory, Warrington, UK.
Serum insulin concentrations were measured with an ELISA kit Invitrogen; Cat KAQ and Biotek ELx analyzer Biotek Instruments, Vermont, USA.
In the Training Study, prior to blood sampling, participants placed their dominant hand into a heated-air box set to 55°C. After 15 minutes of rest, a catheter was placed retrograde into a dorsal hand vein and 10 mL of arterialized blood was drawn for a baseline sample overnight-fasted state Then a g OGTT was completed and arterialized blood sampled every 15 minutes for 2 hours and processed as detailed above for plasma.
Plasma glucose intra-assay coefficient of variation [CV]: 2. Plasma insulin Mercodia AB; reference and C-peptide Sigma Aldrich; reference EZHCPK concentrations were measured using commercially available ELISA kits intra-assay CV for insulin: 3.
All analysis was done in batch and for a given participant all samples were included on the same plate. For the Acute Study, samples were collected pre-exercise and immediately postexercise and at 3 hours postexercise.
To enable the analysis of the IMTG content, approximately 15 to 20 mg of each sample were embedded in Tissue-Tek OCT Sigma Aldrich, Dorset, UK on cork disc and frozen in liquid nitrogen-cooled isopentane before being transferred into an aluminium cryotube and stored at —80°C.
Remaining muscle for glycogen and gene expression analysis was frozen in liquid nitrogen and stored at —80°C. In the Acute Study, the pre-exercise and immediately postexercise muscle samples were used to measure IMTG content and muscle glycogen concentrations The mRNA expression of 34 metabolic genes was analyzed using a custom RT2 Profiler PCR Array Qiagen, Germantown, MD, USA using the pre-exercise and 3-hour postexercise samples For the Training Study, samples were collected pre- and postintervention with participants in a fasted, resting state, with both samples from their dominant leg.
Muscle was extracted from the needle and frozen in liquid nitrogen before storage at —80°C. Frozen wet muscle 80— mg was freeze dried and powdered, with visible blood and connective tissue removed.
Ice cold lysis buffer 50 mM Tris [pH 7. Samples were homogenized with a dounce homogenizer before 60 minutes incubation 4°C with rotation and 10 minutes centrifugation 4°C and 20 g [relative centrifugal force].
The protein content of the resultant supernatant was measured using a bicinchoninic acid assay. In the Training Study, western blotting was used to measure the content of proteins involved in glucose transport, insulin signaling, and lipid metabolism OXPHOS, CPT-1, CD36, GLUT4, CHC22, CHC17, AMPKα, Akt, AS The methods used have been previously described 18 , and all supplementary material and figures are located in a digital research materials repository The phospholipid composition of skeletal muscle samples was measured by gas-liquid chromatography Citrate synthase activity was measured using a commercially available assay Abcam: reference ab To assess RMR, participants rested in a semi-supine position for 15 minutes before four 5-minute expired air samples were collected The participants were provided with the mouthpiece 1 minute prior to sample collections as a stabilization period , which were collected into a L Douglas bag Hans Rudolph, Kansas City, USA via falconia tubing Baxter, Woodhouse and Taylor Ltd, Macclesfield, UK.
Concurrent measures of inspired air were also made to correct for changes in the ambient O 2 and CO 2 concentrations. Expired O 2 and CO 2 concentrations were measured in a volume of each sample using paramagnetic and infrared transducers Mini HF , Servomex Group Ltd.
Substrate utilization rates were calculated via stochiometric equations 38 , Energy expenditure was calculated assuming that fatty acids, glucose, and glycogen provide To measure free-living PAEE, participants wore an Actiheart TM combined heart rate-accelerometery for 7 days Cambridge Neurotechnology, Papworth, UK 40— Energy expenditure and heart rate values from rest and exercise were entered in the Actiheart software for an individually calibrated model.
Participants were asked to keep a written record of their food and fluid intake for 4 days over a typical 7-day period including a weekend day before and during the last week of the intervention. Weighing scales were provided to increase the accuracy of records. Records were analyzed using Nutritics software Nutritics Ltd.
In the Training Study, a sample size estimation was completed using data from a training study in healthy, lean men With α set at 0. We recruited 30 participants to account for the possibility of an unequal allocation of participants across 3 groups when using a stratified randomization schedule.
A Shapiro-Wilk test was performed to test for normal distribution and if this was not obtained, nonparametric tests eg, Wilcoxon matched-pairs signed-rank tests were employed. In the Acute Study, differences between groups were assessed with paired t - tests or a two-way repeated measures for analysis of variance ANOVA; for variables dependent on time.
In the Training Study, one-way ANOVAs were used to assess differences between groups at baseline and two-way mixed-design ANOVAs were used to assess differences between groups in response to the intervention group x time.
If interaction effects were identified, independent t-tests were used to locate variance, with Holm-Bonferroni step-wise adjustments made. Correlations between variables were explored using Pearson r correlation or Spearman rank R for normal or nonnormal distributions, respectively. The area under the concentration-time curve AUC was calculated via the trapezoid rule and divided by the duration of an observation period of interest for a time-averaged summary value.
Statistical analyses were completed on IBM SPSS statistics V22 IBM, Armonk, NY, USA for windows except for the Holm-Bonferroni adjustments, which were completed on Microsoft Excel , and GraphPad Prism V7 GraphPad, San Diego, CA, USA was used to prepare the figures.
As we were unable to collect data from all participants for all measured outcomes, the n are always displayed in all figure and table captions. Exercise before nutrient ingestion increases whole-body and skeletal muscle lipid utilization but does not differentially modulate muscle gene expression. In the Acute Study, exercising before versus after nutrient provision increased the acute plasma glucose and serum insulin responses to food consumption Fig.
The plasma glucose AUC was 6. The serum insulin AUC was Exercise performed before versus after nutrient provision resulted in higher glycerol and NEFA concentrations during the exercise Fig. Plasma glucose A , serum insulin B , plasma glycerol C , and plasma NEFA D concentrations and whole-body carbohydrate E and lipid F utilization rates.
Panel J shows representative images from IMTG staining where IMTG stained green in combination with dystrophin to identify the cell border and stained red is shown from skeletal muscle samples of a representative participant for the carbohydrate-exercise and exercise-carbohydrate trials.
White I shows type 1 fibers, and all other fibers are assumed to be type II. Yellow bars are scale 50 μm. The difference between PRE versus POST exercise is designated by a ; and the difference between BREAKFAST-EXERCISE versus EXERCISE-BREAKFAST is designated by b.
Nutrient provision before exercise potently altered whole-body metabolism, resulting in an increase in whole-body carbohydrate utilization Fig. Muscle was sample pre-exercise and at 3 hours postexercise vastus lateralis to assess the intramuscular gene expression responses to exercise.
The difference between EXERCISE-BREAKFAST vs BREAKFAST-EXERCISE. In the Training Study, rates of whole-body lipid utilization were around 2-fold higher with exercise before versus after carbohydrate provision, and this difference between the conditions was sustained throughout the whole 6-week intervention Fig.
This was accompanied by a decrease in rates of whole-body carbohydrate utilization during exercise Fig. However, cumulative energy expenditure throughout the exercise intervention did not differ with exercise performed before versus after carbohydrate provision Fig.
The change in the OGIS index in response to exercise training was positively and moderately correlated with cumulative lipid utilization during exercise throughout the intervention Fig.
Abbreviations: HOMA-IR, the homeostatic model of insulin resistance; NEFA, non-esterified fatty acid; TAG, triglyceride, HDL, high-density lipoprotein; LDL, low-density lipoprotein. Panels E and F display Pearson correlations between changes in the OGIS index and cumulative lipid utilization and energy expenditure throughout the exercise training intervention, respectively.
Body mass A , the waist-to-hip ratio B , peak fat utilization rates during an incremental exercise test C , and D whole-body oxidative capacity VO 2 peak at baseline, week 3, and week 6 of an intervention in control no-exercise , carbohydrate-exercise, and exercise-carbohydrate groups.
No clear time x group interaction effects were determined for any of the measured fatty acid species except for the proportion of , which increased with exercise before carbohydrate provision compared to the control group The change in the overall saturated fatty acid content of skeletal muscle phospholipids was moderately and positively correlated with changes in postprandial insulinemia, and the relationship was robust to the exclusion of any single data point Fig.
A Pearson correlation between postprandial insulinemia with the change in the proportion of saturated fatty acids in skeletal muscle phospholipids. Skeletal muscle activated protein kinase AMPK protein levels increased approximately 3-fold with exercise training performed before, but not after, carbohydrate provision versus a no-exercise control group Fig.
When we examined the CHC22 isoform alone [data not shown but available online 36 ], we noted baseline differences that may have confounded the interpretation of these fold changes due to regression to the mean.
Pre- to postintervention changes in the levels of energy-sensing proteins and proteins involved in insulin-sensitive GLUT4 trafficking in skeletal muscle A and B. Representative immunoblots are shown C for each protein including those reported in text but not shown in this figure from the same representative participant as well as the loading controls used.
This is the first study to investigate the effect of nutrient-exercise interactions on key aspects of metabolic health in people classified as overweight or obese during moderate-intensity exercise training. We then used a 6-week training program to reveal sustained, 2-fold increases in lipid utilization that were maintained throughout 6 weeks of exercise training performed before versus after carbohydrate ingestion.
An OGTT-derived estimate of peripheral insulin sensitivity the OGIS index increased with exercise training before versus after nutrient provision albeit with no within-group changes , and this was associated with increased lipid utilization during the exercise training intervention.
Exercise training prior to carbohydrate provision also augmented remodeling of phospholipids and increased the levels of energy sensing ie, AMPK and glucose transport proteins ie, GLUT4 in exercised skeletal muscle. These results indicate that nutrient-exercise timing modulates training responsiveness in men who are overweight and links lipid utilization during exercise to training-induced changes in key aspects of metabolic health.
First, we showed that a single bout of exercise performed before versus after nutrient intake increased whole-body lipid utilization Acute Study. A blunting of IMTG utilization has been shown in type I fibers of lean, healthy men in response to carbohydrate ingestion before and during exercise, compared to exercise in the fasted state Here we demonstrated for the first time that exercise before versus after a carbohydrate-rich breakfast increases net IMTG utilization in men classified as overweight or obese.
While the authors do acknowledge that absolute IMTG content may have been underestimated due to the analytical procedures used to estimate IMTG ie, use of Triton X Sigma-Aldrich, Gillingham, Dorset, UK detergent, overnight drying of mounting medium , all samples were treated consistently.
We also showed that net skeletal muscle glycogen utilization and acute skeletal muscle mRNA responses were largely unaffected by the same exercise performed before versus after the breakfast. This is important because muscle glycogen availability can alter muscle adaptations to exercise training Lower muscle glycogen concentrations are therefore unlikely to have driven the training responses we observed in the Training Study with the present method of nutrient-exercise timing.
Altering substrate availability can also drive adaptive responses to exercise partly by modulating acute mRNA expression in exercised skeletal muscle However, in the present study, only 1 measured gene was differentially expressed in response to exercise before versus after a mixed-macronutrient, carbohydrate-rich breakfast.
Specifically, we observed less of an exercise-induced increase in skeletal muscle PPARδ expression with exercise before versus after nutrient provision, which is surprising given that PPARδ has been implicated in adaptations relating to oxidative capacity and lipid utilization The different response observed in the present study might be because we assessed the effect of nutrient-exercise timing ie, nutrient provision before versus after exercise rather than the omission versus ingestion of nutrients.
While it is possible that some changes in mRNA expression were missed due to the timing of muscle biopsies, this result suggests that inferences cannot necessarily be extrapolated from studies assessing the effects of nutrient ingestion versus nutrient omission to inform responses to models of nutrient-exercise timing.
In the Training Study, we then showed that the acute increases in whole-body lipid utilization during a single bout of exercise performed before versus after nutrient intake were sustained throughout 6 weeks of exercise training.
Moreover, only exercise training performed before carbohydrate ingestion reduced postprandial insulinemia and increased the OGGT-derived estimate of peripheral insulin sensitivity ie, the OGIS index.
As the plasma C-peptide-to-insulin ratio was not differentially altered by nutrient-exercise timing, the reduction in postprandial insulinemia with exercise performed before versus after carbohydrate ingestion is likely to be due to a reduction in insulin secretion rather than an increase in hepatic insulin extraction It should also be noted that difference between the exercise groups for the change in the OGIS index was also broadly equivalent to the difference between individuals classified as having a healthy phenotype compared to individuals with impaired glucose tolerance Therefore, when the present data are taken in light of these previous findings, it is likely that nutrient timing is more important for driving exercise-induced adaptations in postprandial metabolism at moderate rather than high-exercise intensities.
Skeletal muscle phospholipid composition is thought to play a role in mediating insulin sensitivity, with a relatively low content of saturated fatty acids correlating with higher insulin sensitivity In support of this prior evidence, the present study demonstrated that the change in the sum of all saturated fatty acids within skeletal muscle phospholipids correlated with the change in postprandial insulinemia.
Single-leg exercise training has been used to show increased polyunsaturated fatty acid content of skeletal muscle phospholipids in an exercised versus non-exercised leg Since that change was independent of dietary intake, the reduction in the saturated fatty content of phospholipids was likely due to a preferential upregulation of saturated fatty acid oxidation as a result of the higher energy expenditure 53 , However, because this previous work involved changes in energy expenditure across experimental conditions, the role of lipid utilization independent of energy expenditure on phospholipid remodeling could not be explored.
It should be acknowledged that at the level of individual fatty acids, the only substantial change in the current study was for an increase in the saturated fatty acid stearate with exercise training performed before versus after carbohydrate intake.
The present study may, however, lack the statistical power to detect changes in other fatty acids as the skeletal muscle phospholipid analysis was only possible on a limited number of participants where tissue sample size allowed. Therefore, more work is required to characterize the specific fatty acid compositional changes in skeletal muscle phospholipids and other lipid pools with changes in nutrient-exercise timing.
AMPK is also nutrient sensitive and contributes to regulation of fatty acid utilization 55 , mitochondrial biogenesis 56 , and the expression of proteins involved in skeletal muscle glucose uptake, including GLUT4 and AS 57—59 , which are key players in whole-body insulin sensitivity We observed greater increases in the protein content of AMPK in skeletal muscle with exercise training before versus after nutrient intake.
The increase in the GLUT4 content of skeletal muscle we observed with exercise before nutrient provision may be explained by this heightened AMPK response and, in turn, may have contributed to increases in the OGIS index following exercise training before versus after nutrient provision Skeletal muscle AMPK can be activated by increased fatty acid availability, independent of muscle glycogen and AMP concentrations Muscle glycogen utilization can modulate AMPK and GLUT4 mRNA expression with different exercise models However, since we observed no difference in muscle glycogen utilization with altered carbohydrate availability during exercise in the Acute Study, the change in the GLUT4 content with exercise training before versus after carbohydrate ingestion is likely to be attributable to repeated increases in fatty acid availability, potentially through increases in the skeletal muscle AMPK content.
However, it should also be noted that the acute and training experiments in this study provided different nutrients as the breakfast ie, a mixed-macronutrient carbohydrate-rich meal versus a carbohydrate drink. As such, some inferences regarding the translation of the acute responses to the longer-term training responses should be interpreted cautiously.
Finally, the AMPK antibody we used detects both isoforms of the catalytic subunits of AMPK AMPKα1 and α2. In human skeletal muscle, three different complexes have been described [α2β2γ1, α2β2γ3, and α1β2γ1; 63 ], and our antibody captured all complexes. Accordingly, we cannot speculate whether a specific heterotrimeric AMPK complex is predominately contributing to the increase in AMPK content we report.
As such, the effect of nutrient-exercise timing on AMPK activation warrants further investigation. The correct targeting and sequestration of GLUT4 into its intracellular insulin-responsive compartments is also important for insulin sensitivity in skeletal muscle 64 , Clathrin heavy-chain isoform 22 CHC22 plays a specialized role in regulating GLUT4 sequestration in human skeletal muscle 66 , protecting GLUT4 from degradation 67 and making it more available for insulin-stimulated release.
We showed an increase in CHC22 protein levels in exercised muscle relative to the exercise effects on CHC17 protein levels with exercise before versus after nutrient provision. As the cognate clathrin CHC17 plays a widespread membrane traffic role in many tissues, CHC17 levels provide a benchmark for general membrane traffic changes compared to those in the GLUT4 pathway The relative increase in CHC22 levels we observed suggests that exercise before nutrient provision not only augments GLUT4 protein levels, but potentially also the machinery necessary for the appropriate sequestration and targeting of GLUT4 to its insulin-responsive compartment.
Objective: We hypothesized that during weight loss, consuming most energy in the morning improves insulin sensitivity and reduces hepatic fat content more than consuming most energy in the evening. Methods: Twenty-three obese insulin resistant men age Insulin sensitivity, measured with a two-step hyperinsulinemic euglycemic clamp using a glucose tracer, intrahepatic triglycerides IHTG , measured using magnetic resonance spectroscopy, and resting energy expenditure REE were assessed before and after the diet intervention.
Results: Meal macronutrient composition and weight loss 6.
Nutrient timing for insulin sensitivity Pre-exercise nutrient availability eensitivity acute metabolic Sunflower seed butter to exercise, which could modulate Nutriient responsiveness. Nutrjent Nutrient timing for insulin sensitivity timng acute and chronic effects of exercise performed before versus after Body fat estimation ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism. Design: 1 Acute, randomized, crossover design Acute Study ; 2 6-week, randomized, controlled design Training Study. Setting: General community. Interventions: Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast Acute Study or carbohydrate Training Study ingestion. Results: Acute Study -exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I net change:
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