Obesity, excess adipose tissue accumulation that may impair health, is a major global healthcare challenge that increases the risk of several life-limiting diseases, reduces quality of life and leads to premature mortality. Weight loss improves or leads to the resolution of obesity-related diseases. Lifestyle interventions are the cornerstone for all weight management programmes and lead to health benefits. However, for the majority of people with severe obesity, lifestyle interventions and currently available anti-obesity medications lead to insufficient weight loss to improve their health. For these patients the only effective treatment option is bariatric surgery, which whilst highly effective, is difficult to access and not suitable for everyone, leaving a ‘treatment gap’ between lifestyle interventions and bariatric surgery. Unfortunately, the history of development of drugs to treat obesity has been marred by poor efficacy and safety issues. This is now set to change as a result of scientific advancements, which have increased the understanding of the role that gut hormones play in regulating energy and glucose homoeostasis. This has led to the development of effective, safe drugs based on gut hormones that target the body's own appetite regulating systems that herald a new era of treatments for people living with obesity.

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.

The short-term effect of soya protein, polydextrose and their combination on energy intake (EI) was investigated in Chinese. In total, twenty-seven healthy, normotensive and lean Chinese men aged 21–40 years were given four different soyabean curd preloads with or without polydextrose. The study was a repeated-measure, randomised, cross-over design. The consumption of high-protein soyabean curd alone or in addition with polydextrose as a preload led to greater reduction in EI at a subsequent meal. A similar observation was also found after intake of low-protein soyabean curd with polydextrose. The gut hormone responses mirrored the reduction in food intake. It appears that incorporation of polydextrose either with low- or high-protein soyabean curd could be a potential strategy to reduce EI and assist with weight management. The popular consumption of soyabean curd in Chinese makes it an ideal vehicle for incorporation of polydextrose. This evidence-based dietary approach can serve as a guideline for developing functional foods for weight reduction and weight maintenance.

The belief that breakfast is the most important meal of day has been derived from cross-sectional studies that have associated breakfast consumption with a lower BMI. This suggests that breakfast omission either leads to an increase in energy intake or a reduction in energy expenditure over the remainder of the day, resulting in a state of positive energy balance. However, observational studies do not imply causality. A number of intervention studies have been conducted, enabling more precise determination of breakfast manipulation on indices of energy balance. This review will examine the results from these studies in adults, attempting to identify causal links between breakfast and energy balance, as well as determining whether consumption of breakfast influences exercise performance. Despite the associations in the literature, intervention studies have generally found a reduction in total daily energy intake when breakfast is omitted from the daily meal pattern. Moreover, whilst consumption of breakfast supresses appetite during the morning, this effect appears to be transient as the first meal consumed after breakfast seems to offset appetite to a similar extent, independent of breakfast. Whether breakfast affects energy expenditure is less clear. Whilst breakfast does not seem to affect basal metabolism, breakfast omission may reduce free-living physical activity and endurance exercise performance throughout the day. In conclusion, the available research suggests breakfast omission may influence energy expenditure more strongly than energy intake. Longer term intervention studies are required to confirm this relationship, and determine the impact of these variables on weight management.

Certain purified indigestible carbohydrates such as inulin have been shown to stimulate gut-derived hormones involved in glycaemic regulation and appetite regulation, and to counteract systemic inflammation through a gut microbiota-mediated mechanism. Less is known about the properties of indigestible carbohydrates intrinsic to food. The aim of this study was to investigate the possibility to affect release of endogenous gut hormones and ameliorate appetite control and glycaemic control by ingestion of a whole-grain cereal food product rich in NSP and resistant starch in healthy humans. In all, twenty middle-aged subjects were provided with a barley kernel-based bread (BB) or a reference white wheat bread during 3 consecutive days, respectively, in a randomised cross-over design study. At a standardised breakfast the following day (day 4), blood was collected for the analysis of blood (b) glucose regulation, gastrointestinal hormones, markers of inflammation and markers of colonic fermentation; 3 d of intervention with BB increased gut hormones in plasma (p) the next morning at fasting (p-glucagon-like peptide-1; 56 %) and postprandially (p-glucagon-like peptide-2; 13 % and p-peptide YY; 18 %). Breath H2 excretion and fasting serum (s) SCFA concentrations were increased (363 and 18 %, respectively), and b-glucose (22 %) and s-insulin responses (17 %) were decreased after BB intervention. Insulin sensitivity index (ISIcomposite) was also improved (25 %) after BB. In conclusion, 3 d of intervention with BB increased systemic levels of gut hormones involved in appetite regulation, metabolic control and maintenance of gut barrier function, as well as improved markers of glucose homoeostasis in middle-aged subjects, altogether relevant for the prevention of obesity and the metabolic syndrome.

The enterohormone glucagon-like peptide-1 (GLP-1) is required to amplify glucose-induced insulin secretion that facilitates peripheral glucose utilisation. Alteration in GLP-1 secretion during obesity has been reported but is still controversial. Due to the high adaptability of intestinal cells to environmental changes, we hypothesised that the density of GLP-1-producing cells could be modified by nutritional factors to prevent the deterioration of metabolic condition in obesity. We quantified L-cell density in jejunum samples collected during Roux-en-Y gastric bypass in forty-nine severely obese subjects analysed according to their fat consumption. In mice, we deciphered the mechanisms by which a high-fat diet (HFD) makes an impact on enteroendocrine cell density and function. L-cell density in the jejunum was higher in obese subjects consuming >30 % fat compared with low fat eaters. Mice fed a HFD for 8 weeks displayed an increase in GLP-1-positive cells in the jejunum and colon accordingly to GLP-1 secretion. The regulation by the HFD appears specific to GLP-1-producing cells, as the number of PYY (peptide YY)-positive cells remained unchanged. Moreover, genetically obese ob/ob mice did not show alteration of GLP-1-positive cell density in the jejunum or colon, suggesting that obesity per se is not sufficient to trigger the mechanism. The higher L-cell density in HFD-fed mice involved a rise in L-cell terminal differentiation as witnessed by the increased expression of transcription factors downstream of neurogenin3 (Ngn3). We suggest that the observed increase in GLP-1-positive cell density triggered by high fat consumption in humans and mice might favour insulin secretion and therefore constitute an adaptive response of the intestine to balance diet-induced insulin resistance.

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 (n 18, 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 (P< 0·01) in the 5 h period after both meals. Plasma essential AA concentrations were greatest within 60 min of each meal for the NPAA diet, but remained elevated for 3–5 h after the HP diet. The three WL diets showed no difference for either fasting concentrations or the postprandial net incremental AUC (net AUCi) for insulin, ghrelin or PYY. No strong correlations were observed between composite hunger scores and net AUCi for 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.

The negative effects of malnourishment in utero have been widely explored; the effects of increased maternal macronutrient intake are not known in relation to high fibre, and have been inconclusive with regard to high protein. In the present study, virgin Wistar dams were fed either a control (C), high-protein (40 %, w/w; HP) or high-prebiotic fibre (21·6 %, w/w; HF) diet throughout pregnancy and lactation. Pups consumed the C diet from 3 to 14·5 weeks of age, and then switched to a high-fat/sucrose diet for 8 weeks. A dual-energy X-ray absorptiometry scan and an oral glucose tolerance test were performed and plasma satiety hormones measured. The final body weight and the percentage of body fat were significantly affected by the interaction between maternal diet and offspring sex: weight and fat mass were higher in the female offspring of the HP v. HF dams. No differences in body weight or fat mass were seen in the male offspring. There was a significant sex effect for fasting and total AUC for ghrelin and fasting GIP, with females having higher levels than males. Liver TAG content and plasma NEFA were lower in the offspring of high-prebiotic fibre dams (HF1) than in those of high-protein dams (HP1) and control dams (C1). Intestinal expression of GLUT2 was decreased in HF1 and HP1 v. C1. The maternal HP and HF diets had lasting effects on body fat and hepatic TAG accumulation in the offspring, particularly in females. Whereas the HP diet predisposes to an obese phenotype, the maternal HF diet appears to reduce the susceptibility to obesity following a high-energy diet challenge in adulthood.

Gut hormones play key roles in the regulation of energy homeostasis. However, little is known about the long- and short-term effects of changing dietary fat content on gut hormones. We aim to examine the effects of changing dietary fat content on plasma gut hormone concentrations in diet-induced obese (DIO) and diet-resistant (DR) rats. After inducing obesity with a high-fat (HF) diet, male Sprague–Dawley rats were divided into three groups according to their body-weight gain: DIO; DR; control (CON). The DIO and DR rats were further divided in random into two groups. One continued on a HF diet and the other switched to a low-fat (LF) diet for an additional 4 weeks. Finally, each group was randomly divided into three subgroups (n 8): fasted; fasted-refed HF; fasted-refed LF diet groups. Replacing a HF diet with a LF diet for 4 weeks resulted in less fat mass, higher fasting and post-HF plasma ghrelin concentration and lower postprandial plasma cholecystokinin concentration in the DIO and DR rats. Acute switching dietary fat resulted in significantly higher post-HF plasma ghrelin concentrations than post-LF ghrelin concentrations in the DR rats on LF diet (DRLF) and DIO rats on LF diet (DIOLF) rats, and significantly higher post-HF obestatin concentrations than post-LF obestatin concentrations in the CON, DR rats on HF diet (DRHF) and DRLF rats. Dietary fat content appears to play a role in the gut hormone profile, which may consequently influence fat mass.

Much interest has been focused on the relationship between glycaemic index and body-weight loss, some of which is fuelled by popular media. However, there is a number of potential mechanisms that could be triggered by reducing the glycaemic index of the carbohydrate consumed in the diet. For example, the effect of foods on the gastrointestinal tract and the effect on blood glucose both could lead to potential appetite effects. Acute meal studies seem to point to an effect of glycaemic index on appetite regulation. However, the results of longer-term studies of weight loss are not as clear. In the present review a possible reason for this variation in outcome from the weight-loss studies will be discussed. The present review focuses on the possibility that the fermentable fibre content of the low-glycaemic-index diet may be important in weight-loss efficacy. A novel receptor that binds SCFA, the products of carbohydrate fermentation, has recently been described on the enteroendocrine L-cell in the colon. This cell releases a number of anorectic hormones and could offer an explanation of the appetite suppressant effects of fermentable carbohydrates. It could also explain the variability in the results of glycaemic-index weight-loss studies.

The obesity epidemic and its associated morbidity and mortality have led to major research efforts to identify mechanisms that regulate appetite. Gut hormones have recently been found to be an important element in appetite regulation as a result of the signals from the periphery to the brain. Candidate hormones include ghrelin, peptide YY, glucagon-like peptide-1 and gastric inhibitory polypeptide, all of which are currently being investigated as potential obesity treatments. Bariatric surgery is currently the most effective therapy for substantial and sustained weight loss. Understanding how levels of gut hormones are modulated by such procedures has greatly contributed to the comprehension of the underlying mechanisms of appetite and obesity. The present paper is a review of how appetite and levels of gastrointestinal hormones are altered after bariatric surgery. Basic principles of common bariatric procedures and potential mechanisms for appetite regulation by gut hormones are also addressed.