The Effect of High-Fat Diet on Intramyocellular Lipid Content in Healthy Adults: A Systematic Review, Meta-Analysis, and Meta-Regression.

Fatty acids are stored within the muscle as intramyocellular lipids (IMCL). Some, but not all, studies indicate that following a high-fat diet (HFD), IMCL may accumulate and affect insulin sensitivity. This systematic review and meta-analysis aimed to quantify the effects of an HFD on IMCL. It also explored the potential modifying effects of HFD fat content and duration, IMCL measurement technique, physical activity status, and the associations of IMCL with insulin sensitivity. Five databases were systematically searched for studies that examined the effect of ≥3 d of HFD (>35% daily energy intake from fat) on IMCL content in healthy individuals. Meta-regressions were used to investigate associations of the HFD total fat content, duration, physical activity status, IMCL measurement technique, and insulin sensitivity with IMCL responses. Changes in IMCL content and insulin sensitivity (assessed by hyperinsulinemic-euglycemic clamp) are presented as standardized mean difference (SMD) using a random effects model with 95% confidence intervals (95% CIs). Nineteen studies were included in the systematic review and 16 in the meta-analysis. IMCL content increased following HFD (SMD = 0.63; 95% CI: 0.31, 0.94, P = 0.001). IMCL accumulation was not influenced by total fat content (P = 0.832) or duration (P = 0.844) of HFD, physical activity status (P = 0.192), or by the IMCL measurement technique (P > 0.05). Insulin sensitivity decreased following HFD (SMD = -0.34; 95% CI: -0.52, -0.16; P = 0.003), but this was not related to the increase in IMCL content following HFD (P = 0.233). Consumption of an HFD (>35% daily energy intake from fat) for ≥3 d significantly increases IMCL content in healthy individuals regardless of HFD total fat content and duration of physical activity status. All IMCL measurement techniques detected the increased IMCL content following HFD. The dissociation between changes in IMCL and insulin sensitivity suggests that other factors may drive HFD-induced impairments in insulin sensitivity in healthy individuals. This trial was registered at PROSPERO as CRD42021257984.

Anorexia of ageing is associated with elevated fasted and lower post-prandial ghrelin, independent of ghrelin O-acyltransferase.

The role of ghrelin metabolism in anorexia of ageing is unclear. The aim of this study was to determine acyl-ghrelin, total ghrelin, and ghrelin O-acyltransferase concentrations when fasted and in responses to feeding in older adults exhibiting anorexia of ageing. Twenty-five older adults (OA; 15f, 74 ± 7 years, 24.5 kg·m-2) and twelve younger adults (YA; 6f, 21 ± 2 years, 24.4 kg·m-2) provided a fasted measure of subjective appetite and fasted blood sample (0 min) before consuming a standardised porridge breakfast meal (450 kcal). Appetite was measured every 30 min for 240 min and blood was sampled at 30, 60, 90, 120, 180 and 240 min while participants rested. At 240 min, an ad libitum pasta-based lunch meal was consumed. Older adults were identified as those with healthy appetite (HA-OA) or low appetite (LA-OA), based on habitual energy intake, self-report appetite, BMI, and ad libitum lunch intake. YA ate more at lunch (1108 ± 235 kcal) than HA-OA (653 ± 133 kcal, p = 0.007) and LA-OA (369 ± 168 kcal; p < 0.001). LA-OA, but not HA-OA, had higher fasted concentrations of acyl- and total ghrelin than YA (acyl-ghrelin: 621 ± 307 pg·mL-1 vs. 353 ± 166 pg·mL-1, p = 0.047; total ghrelin: 1333 ± 702 pg·mL-1 vs. 636 ± 251 pg·mL-1, p = 0.006). Acyl-ghrelin (60 min and 90 min) and total ghrelin (90 min) were suppressed to a greater extent for LA-OA than for YA (p < 0.05). No differences were observed in subjective appetite, acyl-to-total ghrelin ratio, or plasma GOAT content (p > 0.1). Higher fasting ghrelin and an augmented ghrelin response to feeding in LA-OA, but not HA-OA, suggests that alterations to ghrelin metabolism are not functions of ageing per se and may be independent causal mechanisms of anorexia of ageing.

Appetite, food intake, and gut hormone responses to glycomacropeptide protein ingestion in older adults: A feasibility, acceptability, and pilot study.

Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.

Augmented gut hormone response to feeding in older adults exhibiting low appetite.

Age-related changes in gut hormones may play a role in anorexia of ageing. The aim of this study was to determine concentrations of ghrelin, PYY, and GLP-1 in older adults exhibiting an anorexia of ageing phenotype. Thirteen older adults with healthy appetite (OA-HA; 8f, 75 ± 7 years, 26.0 ± 3.2 kg m-2), fifteen older adults with low appetite (OA-LA; 10f, 72 ± 7 years, 23.6 ± 3.1 kg m-2), and twelve young adults (YA; 6f, 22 ± 2 years, 24.4 ± 2.0 kg m-2) completed the study. Healthy appetite and low appetite were determined based on BMI, habitual energy intake, self-reported appetite, and laboratory-assessed ad libitum lunch intake. Participants provided a fasted measure of subjective appetite and blood sample (0 min) before consuming a standardised breakfast (450 kcal). Appetite was measured and blood samples were drawn throughout a 240-min rest period. At 240 min, an ad libitum lunch meal was consumed. Relative intake at lunch (expressed as percentage of estimated total energy requirement) was lower for OA-LA (19.8 ± 7.7%) than YA (41.5 ± 9.2%, p < 0.001) and OA-HA (37.3 ± 10.0%, p < 0.001). Ghrelin suppression was greater for OA-LA (net AUC, -78719 ± 74788 pg mL-1·240min-1) than both YA (-23899 ± 27733 pg mL-1·240min-1, p = 0.016) and OA-HA (-21144 ± 31161 pg mL-1·240min-1, p = 0.009). There were trends for higher GLP-1 concentrations in OA-LA compared with YA at 90 min (8.85 ± 10.4 pM vs. 1.88 ± 4.63 pM, p = 0.073) and 180 min (5.00 ± 4.71 pM vs. 1.07 ± 2.83 pM, p = 0.065). There was a trend for a greater PYY response for OA-LA compared with OA-HA (net AUC p = 0.062). "Anorexigenic response score" - a composite score of gut hormone responses to feeding - showed greater anorexigenic response in OA-LA, compared with YA and OA-HA. No differences were seen in subjective appetite. These observations suggest augmented anorexigenic responses of gut hormones to feeding may be causal mechanisms of anorexia of ageing.

The Frequency and Severity of Gastrointestinal Symptoms in Rugby Players.

This study aimed to assess the self-reported frequency and severity of gastrointestinal symptoms (GIS) at rest and around rugby training and match play in male and female rugby union players. An online questionnaire was sent to registered rugby union players (sevens or fifteens). Thirteen GIS were assessed alongside perceptions of appetite around rugby and rest using Likert and visual analog scales. Questions investigating a range of medical and dietary factors were included. Three hundred and twenty-five players (male n=271, female n=54) participated in the study. More frequent GIS (at least one GIS experienced weekly/more often) was reported by players at rest (n=203; 62%) compared to around rugby (n=154; 47%). The overall severity of GIS was low (mild discomfort), but a portion of players (33%) did report symptoms of moderate severity around rugby. Female players reported more frequent and severe symptoms compared to male counterparts (p<0.001). Self-reported appetite was significantly lower after matches compared to training. There were no dietary or medical factors associated with GIS severity scores. This study describes GIS characteristics in male and female rugby union players. Half of the players assessed experienced some form of GIS that may affect nutrition, training, or performance, and should thus be a consideration for practitioners supporting this cohort.

APPetite: Validation of a smartphone app-based tool for the remote measure of free-living subjective appetite.

This study determined the validity, reproducibility and usability of a smartphone app - APPetite - for the measure of free-living, subjective appetite. Validity was assessed compared with the criterion tool of pen-and-paper visual analogue scale (VAS) (n=22). Appetite was recorded using APPetite and VAS, one immediately after the other, upon waking and every hour thereafter for twelve hours. This was repeated the next day with the order of tool reversed. Agreement between tools was assessed using Bland-Altman analysis. Reproducibility and usability were assessed in a separate experiment (n=22) of two trials (APPetite vs. VAS), separated by seven days. Appetite was recorded in duplicate upon waking and every hour for twelve hours using APPetite or VAS. Agreement between duplicate measures was assessed using Bland-Altman analysis and coefficient of variation (CV) was compared between tools. Usability was assessed by comparing compliance and by qualitative evaluation. APPetite demonstrated good criterion validity with trivial bias of 1.65 units/mm·hr-1 between APPetite- and VAS-derived AUC appetite scores. Limits of agreement were within a maximum allowed difference of 10%. However, proportional bias was observed. APPetite demonstrated high reproducibility, with minimal bias (-0.578 units·hr-1) and no difference in CV between APPetite and VAS (1.29±1.42% vs 1.54±2.36%, p = 0.64). Compliance was high with APPetite (92.7±8.0%) and VAS (91.6±20.4%, p = 0.81). Ninety percent of participants preferred APPetite, citing greater accessibility, simplified process and easier/quicker use. While proportional bias precludes using APPetite and VAS interchangeably, APPetite appears a valid, reproducible and highly usable tool for measuring free-living appetite in young-to-middle-aged adults.

The effects of an acute resistance exercise bout on appetite and energy intake in healthy older adults.

Ageing is associated with reductions in appetite and food intake leading to unintentional weight loss. Such weight loss, particularly through muscle mass reduction, is associated with muscle weakness and functional decline, which represent predictors of poor health outcomes and contribute to frailty in older adults. Exercise-induced anorexia is an established phenomenon in young adults; however appetite and energy intake (EI) responses to resistance exercise are unknown in older adults. Twenty healthy older adults (68 ± 5 years, BMI 26.2 ± 4.5 kg m-2) undertook two 5-h experimental trials. Participants rested for 30 min before being provided with a standardised breakfast (196 kcal, 75.2% carbohydrate, 8.9% protein and 15.9% fat). Participants then rested for 1-h before completing: 1-h resistance exercise bout followed by 2-h of rest (RE) or, a control condition (CON) where participants rested for 3 h, in a randomised crossover design. Appetite perceptions were measured throughout both trials and on cessation, an ad libitum meal was provided to assess EI. A repeated-mesures ANOVA revealed no significant condition x time interaction for subjective appetite (p = 0.153). However, area under the curve for appetite was significantly lower in the RE compared with CON (49 ± 8 mm h-1 vs. 52 ± 9 mm h-1, p = 0.007, d = 0.27). There was no difference in EI (RE = 681 ± 246 kcal; CON = 673 ± 235 kcal; p = 0.865), suggesting that resistance exercise does not affect EI 2 h post-exercise in older adults despite a significant but modest reduction in appetite over a 5-h period. In conclusion, resistance exercise may be an appropriate means for optimising muscle mass adaptations without attenuating acute EI of older adults.

Galactose Ingested with a High-Fat Beverage Increases Postprandial Lipemia Compared with Glucose but Not Fructose Ingestion in Healthy Men.

BACKGROUND: Fructose ingestion with a high-fat beverage increases postprandial lipemia when compared with glucose. It is unknown whether other sugars, such as galactose, also increase postprandial lipemia. OBJECTIVES: The objective was to assess whether galactose ingestion within a high-fat beverage increases postprandial lipemia relative to glucose or fructose. METHODS: Two experiments were conducted, which contrasted different test drinks under otherwise standardized conditions. In Experiment 1, 10 nonobese men (age: 22 ± 1 y; BMI, 23.5 ± 2.2 kg/2) ingested either galactose or glucose (0.75 g supplemented carbohydrate per⋅kilogram body mass) within a high-fat test drink (0.94 g fat per kilogram body mass). In Experiment 2, a separate group of 9 nonobese men (age: 26 ± 6 y; BMI: 23.5 ± 2.6 kg/m2) ingested either galactose or fructose (identical doses as those in Experiment 1) within the same high-fat test drink. Capillary blood was sampled before and at frequent intervals after ingestion of the test drinks for a 300-min period to determine plasma triacylglycerol, glucose, lactate, nonesterified fatty acid, and insulin concentrations. Paired t tests and 2-way, repeated-measures ANOVA were used to compare conditions within each experiment. RESULTS: The incremental AUC for triacylglycerol was greater following galactose ingestion compared with glucose (127 ± 59 compared with 80 ± 48 mmol⋅L-1 × 300 min, respectively; P = 0.04) but not compared with fructose (136 ± 74 compared with 133 ± 63 mmol⋅L-1 ×300 min, respectively; P = 0.91). Plasma lactate concentrations also increased to a greater extent with galactose compared with glucose ingestion (time-condition interaction: P < 0.001) but not fructose ingestion (time-condition interaction: P = 0.17). CONCLUSIONS: Galactose ingestion within a high-fat beverage exacerbates postprandial lipemia and plasma lactate concentrations compared with glucose but not fructose in nonobese men. These data suggest that galactose metabolism may be more similar to fructose than to glucose, providing a rationale to reassess the metabolic fate of galactose ingestion in humans. This trial was registered at clinicaltrials.gov as NCT03439878.

Differences in circulating appetite-related hormone concentrations between younger and older adults: a systematic review and meta-analysis.

Ageing is associated with reduced appetite and energy intakes. However, the mechanisms underlying this phenomenon are not fully understood. This systematic review and meta-analysis quantified differences in circulating concentrations of appetite-related hormones between healthy older and younger adults. Six databases were searched through 12th June 2018 for studies that compared appetite-related hormone concentrations between older and younger adults. Data were pooled using random-effects meta-analysis and are presented as standardised mean difference (Hedges' g) with 95% confidence intervals (95% CI). Thirty-five studies were included involving 710 older adults (mean ± SD; age: 73 ± 5 years) and 713 younger adults (age: 28 ± 7 years). Compared with younger adults, older adults exhibited higher fasted and postprandial concentrations of the anorectic hormones cholecystokinin (Fasted: SMD 0.41 (95% CI 0.24, 0.57); p < 0.001. Postprandial: SMD 0.41 (0.20, 0.62); p < 0.001), leptin [Fasted: SMD 1.23 (0.15, 2.30); p = 0.025. Postprandial: SMD 0.62 (0.23, 1.01); p = 0.002] and insulin [Fasted: SMD 0.24 (- 0.02, 0.50); p = 0.073. Postprandial: SMD 0.16 (0.01, 0.32); p = 0.043]. Higher postprandial concentrations of peptide-YY were also observed in older adults compared with younger adults [SMD 0.31 (- 0.03, 0.65); p = 0.075]. Compared with younger adults, older adults had lower energy intakes [SMD - 0.98 (- 1.74, - 0.22); p = 0.011], and lower hunger perceptions in the fasted [SMD - 1.00 (- 1.54, - 0.46); p < 0.001] and postprandial states [SMD - 0.31, (- 0.64, 0.02); p = 0.064]. Higher circulating concentrations of insulin, leptin, cholecystokinin and peptide-YY accord with reduced appetite and energy intakes in healthy older adults. Interventions to reduce circulating levels of these hormones may be beneficial for combatting the anorexia of ageing.

A single day of mixed-macronutrient overfeeding does not elicit compensatory appetite or energy intake responses but exaggerates postprandial lipaemia during the next day in healthy young men.

Discrete episodes of overconsumption may induce a positive energy balance and impair metabolic control. However, the effects of an ecologically relevant, single day of balanced macronutrient overfeeding are unknown. Twelve healthy men (of age 22 (sd 2) years, BMI 26·1 (sd 4·2) kg/m2) completed two 28 h, single-blind experimental trials. In a counterbalanced repeated measures design, participants either consumed their calculated daily energy requirements (energy balance trial (EB): 10 755 (sd 593) kJ) or were overfed by 50 % (overfeed trial (OF): 16 132 (sd 889) kJ) under laboratory supervision. Participants returned to the laboratory the next day, after an overnight fast, to complete a mixed-meal tolerance test (MTT). Appetite was not different between trials during day 1 (P>0·211) or during the MTT in the fasted or postprandial state (P>0·507). Accordingly, plasma acylated ghrelin, total glucagon-like peptide-1 and total peptide YY concentrations did not differ between trials during the MTT (all P>0·335). Ad libitum energy intake, assessed upon completion of the MTT, did not differ between trials (EB 6081 (sd 2260) kJ; OF 6182 (sd 1960) kJ; P=0·781). Plasma glucose and insulin concentrations were not different between trials (P>0·715). Fasted NEFA concentrations were lower in OF compared with EB (P=0·005), and TAG concentrations increased to a greater extent on OF than on EB during the MTT (P=0·009). The absence of compensatory changes in appetite-related variables after 1 d of mixed macronutrient overfeeding highlights the limited physiological response to defend against excess energy intake. This supports the concept that repeated discrete episodes of overconsumption may promote weight gain, while elevations in postprandial lipaemia may increase CVD risk.