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Breakfast is considered an important meal for daily appetite control. We examined the effect of high-protein breakfasts on within-day appetite sensations and subsequent ad libitum intake, in men and women. Twenty subjects attended on 4 occasions, to consume in a randomised order high-protein (30% energy) breakfast meals, as, 1) maintenance (MTD) fed to energy requirements (2.67 MJ), 2) a weight-loss (WL) bacon-based meal breakfast (WL-B, 2.13 MJ), 3) a WL-chicken salad (WL-CS, 2.13 MJ) and 4) a WL-smoothie (WL-S, 2.08 MJ). The 3 HP-WL breakfasts elicited differences in hunger (p = 0.007), fullness (p = 0.029), desire to eat (p = 0.006) and prospective consumption (p = 0.020). The WL-B meal reduced hunger (p = 0.002) and enhanced fullness (p = 0.02), compared with the two other WL breakfasts. Although these differences were not reflected in ad libitum energy intake later in the day, a HP breakfast can modify morning satiety, which is important during dieting.

While recent studies in humans indicate that fat-free mass (FFM) is closely associated with energy intake (EI) when in energy balance, associations between fat mass (FM) and EI are inconsistent.The present study used a cross-sectional design to examine the indirect and direct effects of FFM, FM and resting metabolic rate (RMR) on EI in individuals at or close to energy balance.Data for 242 individuals (114 males; 128 females; BMI = 25.7 ± 4.9 kg/mAfter adjusting for age, sex and study, linear regression and mediation analyses indicated that the effect of FFM on EI was mediated by RMR (P 0.05). FM also independently predicted EI, with path analysis indicating a positive indirect association (mediated by RMR; P 0.05), and a stronger direct negative association (P 0.05). Leptin, insulin and insulin resistance failed to predict EI, but cognitive restraint was a determinant of EI and partially mediated the association between FM and EI (P 0.05).While the association between FFM and EI was mediated by RMR, FM influenced EI via two separate and opposing pathways; an indirect 'excitatory' effect (again, mediated by RMR), and a stronger direct 'inhibitory' effect. Psychological factors such as cognitive restraint remain robust predictors of EI when considered alongside physiological determinants of EI, and indeed, have the potential to play a mediating role in the overall expression of EI.

Sustainable diets have low environmental impacts; contribute to food and nutrition security and to healthy life for present and future generations; are protective and respectful of biodiversity and ecosystems; culturally acceptable; accessible; economically fair and affordable; nutritionally adequate, safe and healthy; while optimizing natural and human resources. Globally, 795 million people suffer from hunger, 2 billion people suffer from micronutrient deficiencies. Incongruously, at the very same time, over 1.9 billion adults worldwide are overweight of which 600 million are obese. It is clear that dietary patterns worldwide must change if we are to achieve a sustainable diet. The “Double Food-Environmental Pyramid” shows that human health and environmental protection can fit into one single food model. In the United Kingdom, it has been suggested that with a healthy balanced diet, an environmentally friendly diet could also be accomplished; involving an reduction of meat and processed meat, and an increase in plant-based foods. The consumption of high levels of animal protein and red meat could be detrimental to gut health and associated with increased cardiovascular diseases and cancer mortality in the long term. High-protein plants are ideal to supplement meat-based products in the human diet and will justify the transition towards plant-based protein supplementations. In this context this chapter reviews nutritional, health, and wellbeing aspects of consumption of plant-based foods including aspects of systemic and gut health, satiety, and weight management. The chapter also provides commentaries on the social implications on meat replacement.

With the increasing obesity epidemic comes the search for effective dietary approaches for calorie restriction and weight loss. Here I examine whether fasting is the latest 'fad diet' as portrayed in popular media and discuss whether it is a safe and effective approach or whether it is an idiosyncratic diet trend that promotes short-term weight loss, with no concern for long-term weight maintenance. Fasting has long been used under historical and experimental conditions and has recently been popularised by 'intermittent fasting' or 'modified fasting' regimes, in which a very low-calorie allowance is allowed, on alternate days (ADF) or 2 days a week (5:2 diet), where 'normal' eating is resumed on non-diet days. It is a simple concept, which makes it easy to follow with no difficult calorie counting every other day. This approach does seem to promote weight loss, but is linked to hunger, which can be a limiting factor for maintaining food restriction. The potential health benefits of fasting can be related to both the acute food restriction and chronic influence of weight loss; the long-term effect of chronic food restriction in humans is not yet clear, but may be a potentially interesting future dietary strategy for longevity, particularly given the overweight epidemic. One approach does not fit all in the quest to achieve body weight control, but this could be a dietary strategy for consideration. With the obesity epidemic comes the search for dietary strategies to (i) prevent weight gain, (ii) promote weight loss and (iii) prevent weight regain. With over half of the population of the United Kingdom and other developed countries being collectively overweight or obese, there is considerable pressure to achieve these goals, from both a public health and a clinical perspective. Certainly not one dietary approach will solve these complex problems. Although there is some long-term success with gastric surgical options for morbid obesity, there is still a requirement for dietary approaches for weight management for the overweight and obese population, particularly as invasive interventions carry post-operative risk of death due to complications. Effective dietary interventions are required that promote long-term adherence and sustained beneficial effects on metabolic and disease markers. In general, such interventions need to be palatable and satiating, meet minimal nutritional requirements, promote loss of fat and preserve lean body mass, ensure long-term safety, be simple to administer and monitor and have widespread public health utility. Intermittent fasting or alternate day fasting may be an option for achieving weight loss and maintenance.

There is growing interest in understanding how diet affects the intestinal microbiota, including its possible associations with systemic diseases such as metabolic syndrome. Here we report a comprehensive and deep microbiota analysis of 14 obese males consuming fully controlled diets supplemented with resistant starch (RS) or non-starch polysaccharides (NSPs) and a weight-loss (WL) diet. We analyzed the composition, diversity and dynamics of the fecal microbiota on each dietary regime by phylogenetic microarray and quantitative PCR (qPCR) analysis. In addition, we analyzed fecal short chain fatty acids (SCFAs) as a proxy of colonic fermentation, and indices of insulin sensitivity from blood samples. The diet explained around 10% of the total variance in microbiota composition, which was substantially less than the inter-individual variance. Yet, each of the study diets induced clear and distinct changes in the microbiota. Multiple Ruminococcaceae phylotypes increased on the RS diet, whereas mostly Lachnospiraceae phylotypes increased on the NSP diet. Bifidobacteria decreased significantly on the WL diet. The RS diet decreased the diversity of the microbiota significantly. The total 16S ribosomal RNA gene signal estimated by qPCR correlated positively with the three major SCFAs, while the amount of propionate specifically correlated with the Bacteroidetes. The dietary responsiveness of the individual’s microbiota varied substantially and associated inversely with its diversity, suggesting that individuals can be stratified into responders and non-responders based on the features of their intestinal microbiota.

This study investigated the impact of either type 2 diabetes or obesity, separately or in combination, on the absolute amounts of microparticles (MP) and the pathways by which these are associated with either condition. The concentrations of circulating MP derived from platelets (PMP), leukocytes (LMP) and monocytes (MMP), together with their specific activation markers, were compared in 30 subjects who were characterised across 4 cohorts as obese or type 2 diabetes. The subjects with type 2 diabetes had elevated concentrations of total PMP (P = 0.003), and PMP that were fibrinogen-positive (P = 0.04), tissue factor-positive (P

This study investigated if additional non-starch polysaccharide (NSP) or resistant starch (RS), above that currently recommended, leads to better improvement in insulin sensitivity (IS) than observed with modest weight loss (WL). Obese male volunteers (n = 14) were given an energy-maintenance (M) diet containing 27 g NSP and 5 g RS daily for one week. They then received, in a cross-over design, energy-maintenance intakes of either an NSP-enriched diet (42 g NSP, 2.5 g RS) or an RS-enriched diet (16 g NSP, 25 g RS), each for three weeks. Finally, a high protein (30% calories) WL diet was provided at 8 MJ/day for three weeks. During each dietary intervention, endogenous glucose production (EGP) and IS were assessed. Fasting glycaemia was unaltered by diet, but plasma insulin and C-peptide both decreased with the WL diet (p < 0.001), as did EGP (−11%, p = 0.006). Homeostatis model assessment of insulin resistance improved following both WL (p < 0.001) and RS (p < 0.05) diets. Peripheral tissue IS improved only with WL (57%–83%, p < 0.005). Inclusion of additional RS or NSP above amounts currently recommended resulted in little or no improvement in glycaemic control, whereas moderate WL (approximately 3 kg fat) improved IS.

Aims In the UK, lifestyle intervention is first-line management in Type 2 diabetes. It is unclear what type of diet is most efficacious for improving glycaemic control. This study investigated the effects of an oat-enriched diet on glycaemic control, postprandial glycaemia, inflammation and oxidative stress compared with standard dietary advice. Methods In a randomized crossover design, 27 volunteers with Type 2 diabetes, managed on diet and lifestyle only, were observed for two consecutive 8-week periods following either the oat-enriched diet or re-enforced standard dietary advice. Volunteers attended at baseline (habitual intake) and 8 and 16 weeks. Measurements included basic clinical measurements and fasted and postprandial (3-h) glucose and insulin in response to a healthy test meal. Markers of inflammation and oxidative stress, including high-sensitivity C-reactive protein, interleukin 6, interleukin 18, tumour necrosis factor-alpha, adiponectin, thiobarbituric acid reactive substances, oxygen radical antioxidant capacity, oxidized LDL and urinary isoprostanes, were also measured at fasting and in the postprandial period. Results There were no diet-related effects on glycaemic control or glycaemic or insulinaemic responses to the test meal. Total cholesterol (5.1 ± 1.0 vs. 4.9 ± 0.8 mmol/l, P = 0.019) concentrations declined following the oat-enriched diet compared with standard dietary advice. There was a postprandial decline in adiponectin concentration (P = 0.009), but no effect of dietary intervention. None of the measures of oxidative stress or inflammation were altered by the oat-enriched diet compared with standard dietary advice. Conclusion The oat-enriched diet had a modest impact on lipid lowering, but did not impact on oxidative stress or inflammation in these volunteers with Type 2 diabetes.

Summary SATIN, or SATiety INnovation, is a 5-year European-funded research project to develop and test new food products with satiating qualities to help control appetite, manage weight and combat obesity. It is a €6 million Framework 7 project funded by the European Commission, designed to develop foods that regulate appetite by reducing hunger, accelerating within-meal satiation and enhancing between meal satiety. The SATIN project employs novel food processing methods to modify food structure to produce functional foods for weight management. This article provides a useful summary of the work plans and describes how industry and academia will work together to produce products ready to commercialise and with proven consumer benefits. The SATIN project involves seven small- to medium-sized enterprises, four industry and seven academic partners. SATIN will also seek to educate consumers and other stakeholders about satiety to optimise the impact of weight management outcomes.

Bacterial β-glucuronidase in the human colon plays an important role in cleaving liver conjugates of dietary compounds and xenobiotics, while other glycosidase activities are involved in the conversion of dietary plant glycosides. Here we detected an increase in β-glucuronidase activity in faecal samples from obese volunteers following a high-protein moderate carbohydrate weight-loss diet, compared with a weight maintenance diet, but little or no changes were observed when the type of fermentable carbohydrate was varied. Other faecal glycosidase activities showed little or no change over a fivefold range of dietary NSP intake, although α-glucosidase increased on a resistant starch-enriched diet. Two distinct groups of gene, gus and BG, have been reported to encode β-glucuronidase activity among human colonic bacteria. Degenerate primers were designed against these genes. Overall, Firmicutes were found to account for 96% of amplified gus sequences, with three operational taxonomic units particularly abundant, whereas 59% of amplified BG sequences belonged to Bacteroidetes and 41% to Firmicutes. A similar distribution of operational taxonomic units was found in a published metagenome dataset involving a larger number of volunteers. Seven cultured isolates of human colonic bacteria that carried only the BG gene gave relatively low β-glucuronidase activity that was not induced by 4-nitrophenyl-β-D-glucuronide. By comparison, in three of five isolates that possessed only the gus gene, β-glucuronidase activity was induced.

A recent Cochrane review concluded that low glycaemic index (GI) diets are beneficial in glycaemic control for patients with type 2 diabetes mellitus (T2DM). There are limited UK data regarding the dietary GI in free-living adults with and without T2DM. We measured the energy and macronutrient intake and the dietary GI in a group (n = 19) of individuals with diet controlled T2DM and a group (n = 19) without diabetes, matched for age, BMI and gender. Subjects completed a three-day weighed dietary record. Patients with T2DM consumed more daily portions of wholegrains (2.3 vs. 1.1, P = 0.003), more dietary fibre (32.1 vs. 20.9 g, P < 0.001) and had a lower diet GI (53.5 vs. 57.7, P = 0.009) than subjects without T2DM. Both groups had elevated fat and salt intake and low fruit and vegetable intake, relative to current UK recommendations.CONCLUSIONS:Patients with T2DM may already consume a lower GI diet than the general population but further efforts are needed to reduce dietary GI and achieve other nutrient targets.

With an ageing population, dietary approaches to promote health and independence later in life are needed. In part, this can be achieved by maintaining muscle mass and strength as people age. New evidence suggests that current dietary recommendations for protein intake may be insufficient to achieve this goal and that individuals might benefit by increasing their intake and frequency of consumption of high-quality protein. However, the environmental effects of increasing animal-protein production are a concern, and alternative, more sustainable protein sources should be considered. Protein is known to be more satiating than other macronutrients, and it is unclear whether diets high in plant proteins affect the appetite of older adults as they should be recommended for individuals at risk of malnutrition. The review considers the protein needs of an ageing population (>40 years old), sustainable protein sources, appetite-related implications of diets high in plant proteins, and related areas for future research.

The cellular model of body composition divides the body in body cell mass (BCM), extracellular solids and extracellular fluids. This model has been infrequently applied for the evaluation of weight loss (WL) programmes.(1) To assess changes in body compartments in obese men undergoing fasting, very low calorie diet (VLCD) and low calorie diet (LCD); (2) to evaluate two cellular models for the determination of changes in BCM, fat mass (FM) and body fluids.Three groups of six, obese men participated in a total fast (F) for 6 days, a VLCD (2.5 MJ per day) for 3 weeks or an LCD (5.2 MJ per day) for 6 weeks. Body composition was measured at baseline and after small ( approximately 5%) and moderate ( approximately 10%) WL. FM was measured using a four-compartment model. Total body water (TBW) and extracellular water (ECW) were, respectively, measured by deuterium and sodium bromide dilution and intracellular water (ICW) calculated by difference. Two cellular models were used to measure BCM, FM and body fluids distribution.After about 5%WL changes in TBW were F=-3.2+/-1.2 kg (P0.01), VLCD=-1.2+/-0.6 kg (P0.01), LCD=-0.3+/-0.9 kg(n.s.). The contribution of TBW to total body mass loss was indirectly associated with FM loss. ECW increased during fasting (+1.5+/-3.1 kg, n.s.), decreased during the VLCD (-2.0+/-1.5 kg, P0.05) and remained unchanged at the end of the LCD (-0.3+/-1.6 kg, n.s.). ICW significantly decreased during fasting (-4.7+/-3.9 kg, P0.05) but did not change in the LCD and VLCD groups. The loss of BCM was more significant in the fasting group and it was directly associated with changes in ICW.After a 6-day period of fasting we observed more ICW losses and less fat mobilization compared with VLCD and LCD. The cellular model of body composition is suitable for the characterization of changes in body fluids distribution during WL.

The effects of incremental exercise on appetite, energy intake (EI), expenditure (EE) and balance (EB) in lean men and women were examined. Six men (age 29·7 (sd5·9) years, weight 75·2 (sd15·3) kg, height 1·75 (sd0·11) m) and six women (age 24·7 (sd5·9) years, weight 66·7 (sd9·10) kg, height 1·70 (sd0·09) m) were each studied three times during a 16 d protocol, corresponding to no additional exercise (Nex), moderate-intensity exercise (Mex; 1·5–2·0 MJ/d) and high-intensity exercise (Hex; 3·0–4·0 MJ/d) regimens. Subjects were fed to EB during days 1–2, and during days 3–16 they fedad libitumfrom a medium-fat diet of constant composition. Daily EE, assessed using the doubly labelled water method, was 9·2, 11·6 and 13·7 MJ/d (P sed0·45) for the women and 12·2, 14·0 and 16·7 MJ/d (P = 0·007;sed1·11) for the men on the Nex, Mex and Hex treatments, respectively. EI was 8·3, 8·6 and 9·9 MJ/d (P = 0·118;sed0·72) for the women and 10·6, 11·6 and 12·0 MJ/d (P = 0·031;sed0·47) for the men, respectively. On average, subjects compensated for about 30 % of the exercise-induced energy deficit. However, the degree of compensation varied considerably among individuals. The present study captured the initial compensation in EI for exercise-induced energy deficits. Total compensation would take a matter of weeks.

It has been proposed that the development of obesity in humans is influenced by the relative proportions of the two major phyla of bacteria (Bacteroidetes and Firmicutes) present in the large intestine. To examine the relationships between body mass index, weight loss and the major bacterial groups detected in fecal samples. Major groups of fecal bacteria were monitored using fluorescent in situ hybridization (FISH) in obese and non-obese subjects under conditions of weight maintenance, and in obese male volunteers undergoing weight loss on two different reduced carbohydrate weight-loss diets given successively for 4 weeks each. We detected no difference between obese and non-obese individuals in the proportion of Bacteroidetes measured in fecal samples, and no significant change in the percentage of Bacteroidetes in feces from obese subjects on weight loss diets. Significant diet-dependent reductions in a group of butyrate-producing Firmicutes were, however, detected in fecal samples from obese subjects on weight loss diets. Diets designed to achieve weight loss in obese subjects can significantly alter the species composition of the gut microbiota, but we find no evidence that the proportions of Bacteroidetes and Firmicutes among fecal bacteria have a function in human obesity.

The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO(2)max) and energy intake. There was no significant association between the FTO genotype and BMR or VO(2)max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild-type TT genotype and 10.2 and 9.5 MJ for the "at risk" AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.

The dramatic increase in obesity and associated diseases has focused interest on the influence of dietary ingredients in controlling satiety. Dietary resistant starch (RS), which undergoes colonic ...

High-protein diets are an effective means for weight loss (WL), but the mechanisms are unclear. One hypothesis relates to the release of gut hormones by either protein or amino acids (AA). The present study involved overweight and obese male volunteers (n18, mean BMI 36·8 kg/m2) who consumed a maintenance diet for 7 d followed by fully randomised 10 d treatments with three iso-energetic WL diets, i.e. with either normal protein (NP, 15 % of energy) or high protein (HP, 30 %) or with a combination of protein and free AA, each 15 % of energy (NPAA). Psychometric ratings of appetite were recorded hourly. On day 10, plasma samples were taken at 30 min intervals over two consecutive 5 h periods (covering post-breakfast and post-lunch) and analysed for AA, glucose and hormones (insulin, total glucose-dependent insulinotropic peptide, active ghrelin and total peptide YY (PYY)) plus leucine kinetics (first 5 h only). Composite hunger was 16 % lower for the HP diet than for the NP diet (Pi) for insulin, ghrelin or PYY. No strong correlations were observed between composite hunger scores and net AUCifor either AA or gut peptides. Regulation of hunger may involve subtle interactions, and a range of signals may need to be integrated to produce the overall response.

Comparing reported energy intakes with estimated energy requirements as multiples of basal metabolic rate (Ein:BMR) is an established method of identifying implausible food intake records. The present study aimed to examine the validity of self-reported food intakes believed to be plausible.One hundred and eighty men and women were provided with all food and beverages for two consecutive days in a residential laboratory setting. Subjects self-reported their food and beverage intakes using the weighed food diary method (WDR). Investigators covertly measured subjects' actual consumption over the same period. Subjects also reported intakes over four consecutive days at home. BMR was measured by indirect calorimetry.Average reported energy intakes were significantly lower than actual intakes (11.2 and 11.8 MJ/d, respectively, P0.001). Two-thirds (121) of the WDR were under-reported to varying degrees. Only five of these were considered as implausible using an Ein:BMR cut-off value of 1.03*BMR. Under-reporting of food and beverage intakes, as measured by the difference between reported and actual intake, was evident at all levels of Ein;BMR. Reported energy intakes were lower still (10.2 MJ/d) while subjects were at home.Under-recording of self-reported food intake records was extensive but very few under-reported food intake records were identified as implausible using energy intake to BMR ratios. Under-recording was evident at all levels of energy intake.

The most commonly used predictive equation for basal metabolic rate (BMR) is the Schofield equation, which only uses information on body weight, age and sex to derive the prediction. However, because body composition is a key influencing factor, there will be error in calculating an individual's basal requirements based on this prediction. To investigate whether adding additional anthropometric measures to the standard measures can enhance the predictability of BMR and to cross-validate this within a separate subgroup. Cross-sectional study of 150 Caucasian adults from Scotland, with a body mass index range of 16.7–49.3 kg/m2. All subjects underwent measurement of BMR, body composition, and 148 also had basic skinfold and circumference measures taken. The resultant equation was tested in a subgroup of 39 obese males. The average difference between the predicted (Schofield equation) and measured BMR was 502 kJ/day. There was a slight systematic bias in this error, with the Schofield equation underestimating the lowest values. The average discrepancy between predicted and actual BMR was reduced to 452 kJ/day, with the addition of fat mass, fat-free mass, an overall 10% improvement on the Schofield equation (P=0.054). Using an equation derived from principal components analysis of anthropometry measurements similarly decreased the difference to 458 kJ/day (P=0.039). Testing the equation in a separate group indicated a 33% improvement in predictability of BMR, compared to the Schofield equation. In the absence of detailed information on body composition, utilizing anthropometric data provides a useful alternative methodology to improve the predictability of BMR beyond that achieved from the standard Schofield prediction equation. This should be confirmed in more individuals, both within the obese and normal weight category.

Background:Basalmetabolicrate(BMR)isthelargestcomponent of daily energy demand in Western societies. Previous studies indicated that BMR is highly variable, but the cause of this variation is disputed. All studies agree that variation in fat-free mass (FFM) plays a major role, but effects of fat mass (FM), age, sex, and the hormones leptin, triiodothyrionine (T3), and thyroxine (T4) remain uncertain. Objective: We partitioned the variance in BMR into within- and between-subject effects and explored the roles of FFM, FM, bone mineral content, sex, age, and circulating concentrations of plasma leptin, T3, and T4. Design: This was a cross-sectional study of 150 white adults from northeast Scotland, United Kingdom. Results: Only 2% of the observed variability in BMR was attributable to within-subject effects, of which 0.5% was analytic error. Of the remaining variance, which reflected between-subject effects, 63% was explained by FFM, 6% by FM, and 2% by age. The effects of sex and bone mineral content were not significant (P 0.05). Twenty-sixpercentofthevarianceremainedunexplained.Thisvariation was not associated with concentrations of circulating leptin or T3 .T 4 was not significant in women but explained 25% of the residual variance in men. Conclusions: Our data confirm that both FFM and FM are significant contributors to BMR. When the effect of FM on BMR is removed,anyassociationwithleptinconcentrationsdisappears,which suggests that previous links between circulating leptin concentrations and BMR occurred only because of inadequate control for the effects of FM. Am J Clin Nutr 2005;82:941–8.

A great deal of attention has focused on the central role of alpha melanocyte-stimulating hormone (alpha-MSH) and its antagonism at the melanocortin-4 receptor (MC4R) by agouti related protein (AgRP) in the regulation of energy balance. However, very little is known regarding the function of circulating AgRP and alpha-MSH in humans. We aimed to determine whether circulating alpha-MSH and AgRP are responsive to long-term perturbations in energy balance, in a manner consistent with their central putative functions.Circulating alpha-MSH, AgRP and leptin were measured in both lean (n = 11) and obese (n = 18) male volunteers, some of whom (lean n = 11, obese n = 12) were then allocated one of two weight-loss dietary strategies to achieve about 5% weight loss. This was achieved by either total starvation (for 4-6 days) for rapid weight loss or a very low calorie diet (VLCD, 2.6 MJ/day) (11-12 days) for less rapid weight loss, in both the lean and obese volunteers.At baseline, prior to any weight loss both plasma alpha-MSH (15.8 +/- 1.2 vs. 5.8 +/- 1.0 pmol/l +/- SEM; P0.001) and AgRP (49.4 +/- 2.4 vs. 10.1 +/- 0.9 pg/ml +/- SEM; P0.001) were elevated in obese subjects compared with lean. In both cases this correlated closely with fat mass (P0.001), percentage body fat (P0.001) and leptin (P0.05). Plasma AgRP increased significantly during a 6-day fast in lean individuals (11.1 +/- 1.6 vs. 21.6 +/- 3.1 pg/ml +/- SEM; P0.05) but not in the VLCD subjects or in the obese, while alpha-MSH was not affected by any changes in energy balance in either the lean or the obese volunteers.We show a difference in alpha-MSH and AgRP in lean and obese subjects that correlates closely with body fat at baseline. We demonstrate an increase in plasma AgRP during a 6-day fast in lean individuals that is coincident with a decrease in plasma leptin. This increase in AgRP was not due to weight loss per se as there was no change in AgRP as a result of the same weight loss in the VLCD intervention in lean individuals. The source of the increase in plasma AgRP and its physiological function in the periphery remains to be elucidated but we suggest that the dynamics of the change in plasma leptin may determine the elevation in fasting plasma AgRP in lean subjects.

We assessed the effect of no exercise (Nex; control) and high exercise level (Hex; approximately 4 MJ/day) and two dietary manipulations [a high-fat diet (HF; 50% of energy, 700 kJ/100 g) and low-fat diet (LF; 20% of energy, 300 kJ/100 g)] on compensatory changes in energy intake (EI) and energy expenditure (EE) over 7-day periods. Eight lean men were each studied four times in a 2 x 2 randomized design. EI was directly quantified by weight of food consumed. EE was assessed by heart rate (HR) monitoring. Body weight was measured daily. Mean daily EE was 17.6 and 11.5 MJ/day (P0.001) on the pooled Hex and Nex treatments, respectively. EI was higher on HF diets (13.4 MJ/day pooled) compared with the LF diets (9.0 MJ/day). Regression analysis showed that these energy imbalances induced significant compensatory changes in EB over time of approximately 0.3-0.4 MJ/day (P0.05). These were due to changes in both EI and EE in the opposite direction to the perturbation in energy balance. These changes were significant, small but persistent, amounting to approximately 0.2 and approximately 0.35 MJ/day for EI and EE, respectively.

Objectives: Obesity is associated with increased inactivation of cortisol by hepatic A-ring 5a- and 5b-reductases, impaired hepatic regeneration of cortisol from cortisone by 11b-hydroxysteroid dehydrogenase type 1 (11HSD1), but increased subcutaneous adipose 11HSD1 activity enhancing local cortisol levels in fat. Cause and effect between obesity and abnormal cortisol metabolism is untested. Design: Acute weight loss was induced by very low calorie diet (VLCD) or starvation in obese men. Methods: Otherwise healthy males (aged 20 – 55 years; body mass index (BMI) 30 – 40 kg/m 2 ) were studied after 6 days on a weight maintenance diet; then after either 6 days of starvation (n ¼ 6) or 3 weeks of VLCD (2.55 MJ; n ¼ 6); then after 1 week of weight maintenance; and finally after 2 weeks of being allowed to feed ad libitum. Plasma samples were obtained from indwelling cannulae at 0930 h and 1815 h and a 24 h urine collection was completed for analysis of cortisol metabolites by gas chromatography/mass spectrometry. Results: Data are mean^S.E.M. BMI fell (kg/m 3 ) from 34.8^0.8 at baseline to 31.8^1.4 on VLCD and 32.7^1.1 on starvation. Starvation caused a rise in plasma cortisol (at 0930 h from 143^17 to 216^11 nM, P , 0.001) but no change in total urinary cortisol metabolites. VLCD did not alter plasma cortisol and markedly reduced cortisol metabolite excretion (from 15.8^1.1 mg/day at baseline to 7.0^1.1 mg/day, P , 0.001). Relative excretion of 5a-reduced cortisol metabolites fell on both diets, but there were no changes in cortisol/cortisone metabolite ratios reflecting 11HSD activities. Conclusions: Weight loss with VLCD in obesity reverses up-regulation of hepatic A-ring reductases and normalises cortisol production rate; in contrast, starvation produces acute stress and further activation of cortisol secretion. We suggest that activation of cortisol secretion is not an irreversible intrinsic abnormality in obese patients, and speculate that dietary content has an important influence on the neuroendocrine response to weight loss. European Journal of Endocrinology 150 185–194

Coronary heart disease is the leading cause of death worldwide and accounts for almost 70 000 deaths annually in the UK alone.1 The modifiable lifestyle risk factors contributing to coronary heart disease have been extensively researched and they include poor dietary choices, physical inactivity and smoking. In contrast to the often recommended heart healthy diet, it has perhaps been both a surprise and a delight to many that recent research has suggested that chocolate in both its milky and dark disguises may have a protective effect against coronary artery disease.2 ,3 Cocoa has the richest flavanol content of all foods on a per-weight basis including high levels of epicatechin.4 The health benefits of eating chocolate have increasingly been attributed to their flavan-3-ol content, found in the highest concentration in dark chocolate.5 Indeed, flavanol-rich cocoa is thought to activate nitric oxide synthesis which could explain findings of beneficial effects of chocolate on endothelial cell function and blood pressure control.4 ,5 Chocolate consumption has also been associated with improved platelet function, reduced insulin resistance and a healthier serum lipid profile.4 This may be attributed to the high levels of oleic acid found in dark chocolate—a monounsaturated fat known to have a positive effect on blood lipids. The most recent Swedish study found an inverse association between chocolate consumption and myocardial infarction risk with those eating ≥3–4 servings/week of chocolate having a 13% relative risk reduction (HR 0.87 (95% CI 0.77 to 0.98, p=0.04)) compared with non-consumers.2 The authors acknowledge that chocolate consumption was only assessed by a single question in a baseline food frequency questionnaire with no distinction made between types or quantity. This is particularly important bearing in mind the possible dose-dependent relationship …

It is well established that in human subjects a proportion of urea production undergoes hydrolysis in the gastrointestinal tract with release of N potentially available for amino acid synthesis. Previous studies have suggested adaptive changes in urea kinetics, with more urea-N retained within the metabolic pool during reduced dietary intakes of energy and protein. We therefore investigated the effect of rate and extent of weight loss on adaptive changes in urea kinetics in two groups (eachn6) of obese men (mean age 43 (sd12) years, BMI 34·8 (sd2·9)kg/m2) during either total starvation for 6d or a very-low-energy diet (2·55MJ/d) for 21d. Subjects were resident in the Human Nutrition Unit of the Rowett Research Institute (Aberdeen, Scotland, UK) and lost 6 and 9% initial body weight within the starvation and dieting groups respectively. Changes in urea-N metabolism were assessed by stable isotope tracer kinetics using [15N15N]urea infused intravenously for 36h before, during and after weight loss. In response to weight loss, urea production decreased (P

We assessed the effect of no exercise (Nex; control) and high exercise level (Hex; ∼4 MJ/day) and two dietary manipulations [a high-fat diet (HF; 50% of energy, 700 kJ/100 g) and low-fat diet (LF; ...

Post-prandial hyperglycaemia is predictive of cardiovascular disease risk. Therefore, the International Diabetes Federation (IDF) recommends that 2-hour post-meal glucose should not exceed 7.8mmol/L. There are limited data regarding the extent of post-prandial hyperglycaemia in those with well-controlled type 2 diabetes and how this relates to HbA1c values. Twenty-nine volunteers with diet-controlled type 2 diabetes were recruited (mean HbA1c 50mmol/mol [6.7%], SD 6.5 [0.6]); mean age 62 years [SD 5.8]; mean BMI 31.9kg/m2 [SD 5.3]), and underwent a three-day period of continuous glucose monitoring (CGMS) at home. Compared with volunteers with an HbA1c >48mmol/mol (6.5%), those with an HbA1c ≤48mmol/mol (6.5%) – mean HbA1c 54 (7.1%) vs 44.9mmol/mol (6.3%), p 8mmol/L (703.1 vs 338.5 min, p=0.01). HbA1c showed reasonable correlation with time spent with glucose >8mmol/L (r2=0.48, p

We assessed the effect of graded increases in exercised-induced energy expenditure (EE) on appetite, daily energy intake (EI), total daily EE and body weight in six lean women using a within-subject, repeated measures design.Subjects were each studied three times during 7 day treatments, corresponding to no-exercise (control; Nex; 0 MJ/day), medium exercise level (Mex; approximately 1.9 MJ/day) and high exercise level (Hex; approximately 3.4 MJ/day), with 2 day maintenance beforehand. Subjects self-weighed ad libitum food intake. EE was assessed by continual heart rate monitoring. During waking hours subjects recorded hourly sensations of hunger and appetite.EE amounted to 9.2, 11.0 and 12.1 MJ/day (F (2, 10)=5.67; P=0.023 (s.e.d.=0.87)) on the Nex, Mex and Hex treatments, respectively. The corresponding values for EI were 8.9, 9.2 and 10.0 MJ/day (F (2, 10)=4.80; P=0.035 (s.e.d.=0.36)). There were very weak treatment effects on hunger. Weight loss was significantly different from zero on the Mex and Hex treatments.Markedly increasing EE through exercise produced significant but partial compensations in EI ( approximately 33% of EE due to exercise). Accurate adjustments of El to acute increases in EE are likely to take weeks rather than days.

Objective: To assess the effect of graded increases in exercised-induced energy expenditure (EE) on appetite, energy intake (EI), total daily EE and body weight in men living in their normal environment and consuming their usual diets. Design: Within-subject, repeated measures design. Six men (mean (s.d.) age 31.0 (5.0) y; weight 75.1 (15.96) kg; height 1.79 (0.10) m; body mass index (BMI) 23.3(2.4) kg/m2), were each studied three times during a 9 day protocol, corresponding to prescriptions of no exercise, (control) (Nex; 0 MJ/day), medium exercise level (Mex; ∼1.6 MJ/day) and high exercise level (Hex; ∼3.2 MJ/day). On days 1–2 subjects were given a medium fat (MF) maintenance diet (1.6 × resting metabolic rate (RMR)). Measurements: On days 3–9 subjects self-recorded dietary intake using a food diary and self-weighed intake. EE was assessed by continual heart rate monitoring, using the modified FLEX method. Subjects' HR (heart rate) was individually calibrated against submaximal VO2 during incremental exercise tests at the beginning and end of each 9 day study period. Respiratory exchange was measured by indirect calorimetry. Subjects completed hourly hunger ratings during waking hours to record subjective sensations of hunger and appetite. Body weight was measured daily. Results: EE amounted to 11.7, 12.9 and 16.8 MJ/day (F(2,10)=48.26; P

Objectives Weight loss (WL) is associated with a decrease in total and resting energy expenditure (EE). We aimed to investigate whether (1) diets with different rate and extent of WL determined different changes in total and resting EE and if (2) they influenced the level of adaptive thermogenesis, defined as the decline in total or resting EE not accounted by changes in body composition. Methods Three groups of six, obese men participated in a total fast for 6 days to achieve a 5% WL and a very low calorie (VLCD, 2.5 MJ/day) for 3 weeks or a low calorie (LCD, 5.2 MJ/day) diet for 6 weeks to achieve a 10% WL. A four-component model was used to measure body composition. Indirect calorimetry was used to measure resting EE. Total EE was measured by doubly labelled water (VLCD, LCD) and 24-hour whole-body calorimetry (fasting). Results VLCD and LCD showed a similar degree of metabolic adaptation for total EE (VLCD = − 6.2%; LCD = − 6.8%). Metabolic adaptation for resting EE was greater in the LCD (− 0.4 MJ/day, − 5.3%) compared to the VLCD (− 0.1 MJ/day, − 1.4%) group. Resting EE did not decrease after short-term fasting and no evidence of adaptive thermogenesis (+ 0.4 MJ/day) was found after 5% WL. The rate of WL was inversely associated with changes in resting EE (n = 30, r = 0.− 42, p = 0.01). Conclusions The rate of WL did not appear to influence the decline in total EE in obese men after 10% WL. Approximately 6% of this decline in total EE was explained by mechanisms of adaptive thermogenesis.

The 4-component (4-C) model is the reference method to measure fat mass (FM). Simpler 2-component (2-C) models are widely used to assess FM. We hypothesised that an aggregate 2-C model may improve accuracy of FM assessment during weight loss (WL). One hundred and six overweight and obese men and women were enrolled in different WL programs (fasting, very low energy diet, low energy diet). Body density, bone mineral content, and total body water were measured. FM was calculated using 2-C, 3-C, and 4-C models. Aggregate equations for 2-C, 3-C, and 4-C models were calculated, with the aggregate 4-C model assumed as the reference method. The aggregate approach postulates that the average of the individual estimates obtained from each model is more accurate than the best single measurement. The average WL was −7.5 kg. The agreement between 3-C and 4-C models for FM change was excellent (R2= 0.99). The aggregate 2-C equation was more accurate than individual 2-C estimates in measuring changes in FM. The aggregate model was characterised by a lower measurement error at baseline and post-WL. The relationship between the aggregate 3-C and 4-C component models was highly linear (R2= 0.99), whereas a lower linearity was found for the aggregate 2-C and 4-C model (R2= 0.72). The aggregate 2-C model is characterised by a greater accuracy than commonly applied 2-C equations for the measurement of FM during WL in overweight and obese men and women.

To date, no study has directly and simultaneously measured the discrepancy between what people actually eat and what they report eating under observation in the context of energy balance (EB). The present study aimed to objectively measure the ‘extent’ and ‘nature’ of misreporting of dietary intakes under conditions in which EB and feeding behaviour were continuously monitored. For this purpose, a total of fifty-nine adults were recruited for 12 d, involving two 3 d overt phases and two 3 d covert phases of food intake measurement in a randomised cross-over design. Subjects hadad libitumaccess to a variety of familiar foods. Food intake was covertly measured using a feeding behaviour suite to establish actual energy and nutrient intakes. During the overt phases, subjects were instructed to self-report food intake using widely accepted methods. Misreporting comprised two separate and synchronous phenomena. Subjects decreased energy intake (EI) when asked to record their food intake (observation effect). The effect was significant in women ( − 8 %,PP

Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m2, took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30 % of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake. An18fluoro-deoxyglucose positron emission tomography scan of the brain was conducted at the end of each dietary intervention period, following an overnight fast (n4) or 4 h after consumption of a test meal (n8). On the next day, whole-body ketone and glucose metabolism was quantified using [1,2,3,4-13C]acetoacetate, [2,4-13C]3-hydroxybutyrate and [6,6-2H2]glucose. The composite hunger score was 14 % lower (P= 0·013) for the HPLC dietary intervention than for the HPMC diet. Whole-body ketone flux was approximately 4-fold greater for the HPLC dietary intervention than for the HPMC diet (P

BackgroundInteractions between the diet and intestinal microbiota play a role in health and disease, including obesity and related metabolic complications. There is great interest to use dietary means to manipulate the microbiota to promote health. Currently, the impact of dietary change on the microbiota and the host metabolism is poorly predictable and highly individual. We propose that the responsiveness of the gut microbiota may depend on its composition, and associate with metabolic changes in the host.MethodologyOur study involved three independent cohorts of obese adults (n = 78) from Belgium, Finland, and Britain, participating in different dietary interventions aiming to improve metabolic health. We used a phylogenetic microarray for comprehensive fecal microbiota analysis at baseline and after the intervention. Blood cholesterol, insulin and inflammation markers were analyzed as indicators of host response. The data were divided into four training set - test set pairs; each intervention acted both as a part of a training set and as an independent test set. We used linear models to predict the responsiveness of the microbiota and the host, and logistic regression to predict responder vs. non-responder status, or increase vs. decrease of the health parameters.Principal findingsOur models, based on the abundance of several, mainly Firmicute species at baseline, predicted the responsiveness of the microbiota (AUC = 0.77-1; predicted vs. observed correlation = 0.67-0.88). Many of the predictive taxa showed a non-linear relationship with the responsiveness. The microbiota response associated with the change in serum cholesterol levels with an AUC of 0.96, highlighting the involvement of the intestinal microbiota in metabolic health.ConclusionThis proof-of-principle study introduces the first potential microbial biomarkers for dietary responsiveness in obese individuals with impaired metabolic health, and reveals the potential of microbiota signatures for personalized nutrition.