Objective
The aim of this study was to determine the effects of sustained morning fasting or breakfast consumption on metabolism, energy intake, and appetite in healthy adults with obesity.
Methods
...An independent‐measures randomized controlled trial with baseline and follow‐up laboratory assessment days separated by a 6‐week intervention of either morning fasting (0 kcal until 12:00 pm) or daily breakfast (> 700 kcal by 11:00 am) was performed. Measures included metabolic outcomes (glucose, insulin, nonesterified fatty acids), hormones regulating appetite (total/acylated ghrelin, peptide YY, leptin), and energy expenditure (diet‐induced thermogenesis) parameters throughout a laboratory test day and ad libitum intake following a fixed breakfast.
Results
Allocation to fasting versus breakfast resulted in minimal adaptation as reflected by the metabolic outcomes or the majority of appetite regulatory outcomes for either area under curve or time‐course‐based measures (P > 0.05). Ad libitum lunch intake was not different (P = 0.13), nor was diet‐induced thermogenesis or a composite appetite score (both P > 0.10). However, there was a reduced total area under the curve for peptide YY (P = 0.05) and increased postprandial hunger ratings (P = 0.05) in the breakfast group.
Conclusions
There was little evidence of metabolic adaptation to acute feeding or negative consequences from sustained morning fasting. This indicates that previously observed differences between breakfast consumers and skippers may be acute effects of feeding or may have resulted from other lifestyle factors.
Low skeletal muscle mass (MM) and deteriorated function (sarcopenia) can be a frequent complication in paediatric inflammatory bowel disease (IBD).
To conduct a systematic review of the paediatric ...IBD literature on skeletal muscle function and mass and identify interventions that could affect them.
Systematic searches (EMBASE, Medline, Cochrane library central for registered control trials and Web of Science) were conducted using the terms ‘lean body mass’ (LM), ‘fat free mass' (FFM) or ‘MM’ and ‘IBD’.
Fourteenth studies were included, presenting data from 439 Crohn's disease (CD), 139 ulcerative colitis (UC) and 2 IBD-unclassified participants compared with healthy matched or unmatched groups or reference populations. Six out of 14 studies reported lower LM, whilst 7 studies observed lower MM and FFM in CD patients compared to healthy controls. Research in UC patients reported lower LM in 3 studies, lower MM in 3 studies and lower FFM in 4 studies. Three prospective studies measured the impact of enteral feeding and showed improvement on disease activity and LM or FFM, while one retrospective study did not show any impact on LM.
Despite the variety of experimental approaches and methods used to assess sarcopenia, most studies showed reduction in MM, LM and FFM in IBD. Nutritional intervention may have a positive effect on LM and FFM. Future research should focus on standardizing the terminology and methodologies used in assessing body composition and investigating sarcopenia in diseased and matched healthy control cohorts in adequately powered studies with a longitudinal design.
Adiposity and adipokines are implicated in the loss of skeletal muscle mass with age and in several chronic disease states. The aim of this study was to determine the effects of human obese and lean ...subcutaneous adipose tissue secretome on myogenesis and metabolism in skeletal muscle cells derived from both young (18-30 yr) and elderly (>65 yr) individuals. Obese subcutaneous adipose tissue secretome impaired the myogenesis of old myoblasts but not young myoblasts. Resistin was prolifically secreted by obese subcutaneous adipose tissue and impaired myotube thickness and nuclear fusion by activation of the classical NFκB pathway. Depletion of resistin from obese adipose tissue secretome restored myogenesis. Inhibition of the classical NFκB pathway protected myoblasts from the detrimental effect of resistin on myogenesis. Resistin also promoted intramyocellular lipid accumulation in myotubes and altered myotube metabolism by enhancing fatty acid oxidation and increasing myotube respiration and ATP production. In conclusion, resistin derived from human obese subcutaneous adipose tissue impairs myogenesis of human skeletal muscle, particularly older muscle, and alters muscle metabolism in developing myotubes. These findings may have important implications for the maintenance of muscle mass in older people with chronic inflammatory conditions, or older people who are obese or overweight.
Obesity and insulin resistance are associated with an impaired sensitivity to anabolic stimuli such as dietary protein (anabolic resistance). Omega-3 polyunsaturated fatty acids (n-3 PUFA) may be ...protective against the deleterious effects of saturated fatty acids (SFA) on insulin resistance. However, the contribution of excess fat consumption to anabolic and insulin resistance and the interaction between SFA and n-3 PUFA is not well studied.
The primary aim of this study was to investigate the effects of an oral fat pre-load, with or without the partial substitution of SFA with fish oil (FO)-derived n-3 PUFA, on indices of insulin and anabolic sensitivity in response to subsequent dietary protein and carbohydrate (dextrose) co-ingestion.
Eight middle-aged males with overweight or obesity (52.8 ± 2.0 yr, BMI 31.8 ± 1.4 kg·m−2) ingested either an SFA, or isoenergetic SFA and FO emulsion (FO), or water/control (Con), 4 h prior to a bolus of milk protein and dextrose.
Lipid ingestion (in particular FO) impaired the early postprandial uptake of branched chain amino acids (BCAA) into the skeletal muscle in response to protein and dextrose, and attenuated the peak glycaemic response, but was not accompanied by differences in whole body (Matsuda Index: Con: 4.66 ± 0.89, SFA: 5.10 ± 0.94 and FO: 4.07 ± 0.59) or peripheral (forearm glucose netAUC: Con: 521.7 ± 101.7; SFA: 470.2 ± 125.5 and FO: 495.3 ± 101.6 μmol·min−1·100 g lean mass·min t = 240–420 min) insulin sensitivity between visits. Postprandial whole body fat oxidation was affected by visit (P = 0.024) with elevated rates in SFA and FO, relative to Con (1.85 ± 0.55; 2.19 ± 0.21 and 0.65 ± 0.35 kJ·h−1·kg−1 lean body mass, respectively), however muscle uptake of free fatty acids (FFA) was unaffected.
Oral lipid preloads, consisting of SFA and FO, impair the early postprandial BCAA uptake into skeletal muscle, which occurs independent of changes in insulin sensitivity.
ClinicalTrials.gov Identifier NCT03146286.
It remains unknown whether sustained daily feeding-fasting patterns modify the acute response to specific feedings on a given day.
We conducted a randomized controlled trial to establish if daily ...breakfast consumption or fasting until noon modifies the acute metabolic and appetitive responses to a fixed breakfast and ad libitum lunch.
With the use of a parallel group design, we randomly assigned 31 healthy, lean men and women (22–56 y) to 6 wk of either consuming ≥700 kcal of self-selected items before 1100 or fasting (0 kcal) until 1200 daily. Following 48 h of diet and physical activity standardization, we examined metabolic and appetite responses to a standardized breakfast and ad libitum lunch before and after the intervention. Data were analyzed using 3- and 2-way ANCOVA.
Systemic concentrations of energy balance regulatory hormones total and acylated ghrelin, leptin, and peptide tyrosine-tyrosine) responded similarly to breakfast and lunch before and after 6 wk of either morning fasting or regular breakfast, with the exception of a tendency for increased glucagon-like peptide-1 concentrations from baseline to follow-up in the Breakfast Group compared with a decrease over that period in the Fasting Group P = 0.06, partial eta squared value (ƞ2) = 0.16. Subjective appetite sensations also did not differ over the course of the day, and ad libitum energy intake at lunch was not systematically affected by either intervention, decreasing by 27 kcal (95% CI: −203, 149 kcal) with fasting and by 77 kcal (95% CI: −210, 56 kcal) with breakfast. Similarly, glycemic, insulinemic, lipemic, and thermogenic responses to breakfast and lunch were very stable at baseline and follow-up and, thus, did not differ between treatment groups.
Our results indicate that a sustained period of either extended morning fasting or eating a daily breakfast has minimal effect upon acute metabolic and appetite responses in lean adults. This trial was registered at www.isrctn.org as ISRCTN31521726.
Fibroblast growth factor 21 (FGF21) is increased acutely by carbohydrate ingestion and is elevated in patients with type 2 diabetes (T2D). However, the physiological significance of increased FGF21 ...in humans remains largely unknown. We examined whether FGF21 contributed to the metabolic improvements observed following treatment of patients with T2D with either triple (metformin/pioglitazone/exenatide) or conventional (metformin/insulin/glipizide) therapy for 3 yr. Forty-six patients with T2D were randomized to receive either triple or conventional therapy to maintain HbA1c < 6.5%. A 2-h 75-g oral glucose tolerance test (OGTT) was performed at baseline and following 3 years of treatment to assess glucose tolerance, insulin sensitivity, and β-cell function. Plasma total and bioactive FGF21 levels were quantitated before and during the OGTT at both visits. Patients in both treatment arms experienced significant improvements in glucose control, but insulin sensitivity and β-cell function were markedly increased after triple therapy. At baseline, FGF21 levels were regulated acutely during the OGTT in both groups. After treatment, fasting total and bioactive FGF21 levels were significantly reduced in patients receiving triple therapy, but there was a relative increase in the proportion of bioactive FGF21 compared with that observed in conventionally treated subjects. Relative to baseline studies, triple therapy treatment also significantly modified FGF21 levels in response to a glucose load. These changes in circulating FGF21 were correlated with markers of improved glucose control and insulin sensitivity. Alterations in the plasma FGF21 profile may contribute to the beneficial metabolic effects of pioglitazone and exenatide in human patients with T2D.
In patients with T2D treated with a combination of metformin/pioglitazone/exenatide (triple therapy), we observed reduced total and bioactive plasma FGF21 levels and a relative increase in the proportion of circulating bioactive FGF21 compared with that in patients treated with metformin and sequential addition of glipizide and basal insulin glargine (conventional therapy). These data suggest that FGF21 may contribute, at least in part, to the glycemic benefits observed following combination therapy in patients with T2D.
PURPOSEIngested ethanol (EtOH) is metabolized gastrically and hepatically, which may influence resting and exercise metabolism. Previous exercise studies have provided EtOH intravenously rather than ...orally, altering the metabolic effects of EtOH. No studies to date have investigated the effects of EtOH ingestion on systemic and peripheral (e.g., skeletal muscle) exercise metabolism.
METHODSEight men (mean ± SD; age = 24 ± 5 yr, body mass = 76.7 ± 5.6 kg, height = 1.80 ± 0.04 m, V˙O2peak = 4.1 ± 0.2 L·min) performed two bouts of fasted cycling exercise at 55% V˙O2peak for 2 h, with (EtOH) and without (control) prior ingestion of EtOH 1 h and immediately before exercise (total dose = 0.1 g·kg lean body mass·h; 30.2 ± 1.1 g 40% ABV Vodka; fed in two equal boluses) in a randomized order, separated by 7–10 d.
RESULTSMuscle glycogen use during exercise was not different between conditions (mean normalized 95% confidence interval; EtOH, 229 156–302 mmol·kg dm, vs control, 258 185–331 mmol·kg dm; P = 0.67). Mean plasma glucose concentrations during exercise were similar (control, 5.26 5.22–5.30, vs EtOH, 5.34 5.30–5.38; P = 0.06). EtOH ingestion resulted in similar plasma nonesterified fatty acid concentrations compared with rest (control, 0.43 0.31–0.55 mmol·L, vs EtOH, 0.30 0.21–0.40 mmol·L) and during exercise. Plasma lactate concentration was higher during the first 30 min of rest after EtOH consumption (mean concentration; control, 0.83 0.77–0.90 mmol·L, vs EtOH, 1.00 0.93–1.07 mmol·L), but the response during exercise was similar between conditions.
CONCLUSIONSMuscle glycogen utilization was similar during exercise with or without prior EtOH ingestion, reflected in similar total whole-body carbohydrate oxidation rates observed.
Key points
In lean individuals, 6 weeks of extended morning fasting increases the expression of genes involved in lipid turnover (ACADM) and insulin signalling (IRS2) in subcutaneous abdominal ...adipose tissue.
In obese individuals, 6 weeks of extended morning fasting increases IRS2 expression in subcutaneous abdominal adipose tissue.
The content and activation status of key proteins involved in insulin signalling and glucose transport (GLUT4, Akt1 and Akt2) were unaffected by extended morning fasting. Therefore, any observations of altered adipose tissue insulin sensitivity with extended morning fasting do not necessarily require changes in insulin signalling proximal to Akt.
Insulin‐stimulated adipose tissue glucose uptake rates are lower in obese versus lean individuals, but this difference is abolished when values are normalised to whole‐body fat mass. This suggests a novel hypothesis which proposes that the reduced adipose glucose uptake in obesity is a physiological down‐regulation to prevent excessive de novo lipogenesis.
This study assessed molecular responses of human subcutaneous abdominal adipose tissue (SCAT) to 6 weeks of morning fasting. Forty‐nine healthy lean (n = 29) and obese (n = 20) adults provided SCAT biopsies before and after 6 weeks of morning fasting (FAST; 0 kcal until 12.00 h) or daily breakfast consumption (BFAST; ≥700 kcal before 11.00 h). Biopsies were analysed for mRNA levels of selected genes, and GLUT4 and Akt protein content. Basal and insulin‐stimulated Akt activation and tissue glucose uptake rates were also determined. In lean individuals, lipid turnover and insulin signalling genes (ACADM and IRS2) were up‐regulated with FAST versus BFAST (ACADM: 1.14 (95% CI: 0.97–1.30) versus 0.80 (95% CI: 0.64–0.96), P = 0.007; IRS2: 1.75 (95% CI: 1.33–2.16) versus 1.09 (95% CI: 0.67–1.51), P = 0.03, respectively). In obese individuals, no differential (FAST versus BFAST) expression was observed in genes involved in lipid turnover (all P > 0.1). GLUT4, Akt protein content and insulin‐stimulated Akt phosphorylation were unaffected by FAST versus BFAST in both lean and obese cohorts (all P > 0.1). Lower insulin‐stimulated glucose uptake rates in obese versus lean individuals were eradicated when normalised to whole‐body fat mass (P = 0.416). We conclude that morning fasting up‐regulates lipid turnover genes in SCAT of lean individuals. Secondly, altered SCAT insulin sensitivity with morning fasting is unlikely to be explained by signalling proximal to Akt. Finally, lower insulin‐stimulated SCAT glucose uptake rates in obese individuals are proportional to whole‐body fat mass, suggesting a compensatory down‐regulation, presumably to prevent excessive de novo lipogenesis in adipose tissue. This trial was registered as ISRCTN31521726.
Key points
In lean individuals, 6 weeks of extended morning fasting increases the expression of genes involved in lipid turnover (ACADM) and insulin signalling (IRS2) in subcutaneous abdominal adipose tissue.
In obese individuals, 6 weeks of extended morning fasting increases IRS2 expression in subcutaneous abdominal adipose tissue.
The content and activation status of key proteins involved in insulin signalling and glucose transport (GLUT4, Akt1 and Akt2) were unaffected by extended morning fasting. Therefore, any observations of altered adipose tissue insulin sensitivity with extended morning fasting do not necessarily require changes in insulin signalling proximal to Akt.
Insulin‐stimulated adipose tissue glucose uptake rates are lower in obese versus lean individuals, but this difference is abolished when values are normalised to whole‐body fat mass. This suggests a novel hypothesis which proposes that the reduced adipose glucose uptake in obesity is a physiological down‐regulation to prevent excessive de novo lipogenesis.
Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The ...aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese men 46.4 ± 1.4 yr, body mass index (BMI) 32.3 ± 5.4 kg/m
participated in the acute feeding study, which consisted of two randomized crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion), 4 h before the coingestion of milk protein, intrinsically labeled with 1-
Cphenylalanine, and dextrose. Nine overweight/obese men (44.0 ± 1.7 yr, BMI 30.1 ± 1.1 kg/m
) participated in the chronic study, which consisted of a baseline, 1-wk isocaloric diet, followed by a 2-wk high-fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was twofold higher (
< 0.05) in the lipid trial compared with control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, pyruvate dehydrogenase complex activity, and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle diacylglycerol C16:0 (
= 0.06) and ceramide C16:0 (
< 0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on the skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting that dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.
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