Radhika V. Seimon

Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men

While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals (P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals (P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.

Marked differences in gustatory and gastrointestinal sensitivity to oleic acid between lean and obese men

BACKGROUND Both orosensory stimulation and feedback from the gastrointestinal tract contribute to energy intake regulation. OBJECTIVE We evaluated the hypothesis that overweight or obese subjects would be less sensitive to both oral and intraduodenal oleic acid exposure than would lean subjects. DESIGN Eleven overweight or obese and 8 lean men were studied on 2 occasions, during which antropyloroduodenal pressures, plasma cholecystokinin and peptide YY, and appetite were measured during 90-min intraduodenal infusions of saline or oleic acid (18:1 load: 0.78 kcal/min); energy intake (buffet lunch) was determined immediately afterward. Oral detection thresholds for 18:1 and recent dietary intake (2-d recall) were also quantified. RESULTS In lean subjects, the number of isolated pyloric pressure waves (IPPWs) was greater during 18:1 infusion than during saline infusion (P < 0.05); no significant differences were observed between the 18:1 and saline infusions in the overweight or obese subjects. In both groups, 18:1 stimulated plasma cholecystokinin and peptide YY and suppressed energy intake compared with saline (P < 0.05), with trends for reduced cholecystokinin and energy intake responses in the overweight or obese subjects. Detection thresholds for 18:1 were greater in overweight or obese (7.9 ± 0.1 mmol/L) than in lean (4.1 ± 0.4 mmol/L) subjects (P < 0.05). Overweight or obese subjects had greater recent energy (P < 0.05) and fat (P = 0.07) intakes than did lean subjects. There was a direct relation (r = 0.669) of body mass index with 18:1 detection thresholds and inverse relations (r < -0.51) of IPPWs with body mass index and 18:1 detection thresholds (P < 0.05). CONCLUSIONS The ability to detect oleic acid both orally and within the gastrointestinal tract is compromised in obese men, and oral and gastrointestinal responses to oleic acid are related. This trial was registered at www.actr.org.au (Australian New Zealand Clinical Trials Registry) as 12609000557235.

The droplet size of intraduodenal fat emulsions influences antropyloroduodenal motility, hormone release, and appetite in healthy males

BACKGROUND The presence of fat in the small intestine modulates gastrointestinal motility, stimulates plasma cholecystokinin and peptide YY release, and suppresses appetite and energy intake. These effects are dependent on the lipolysis of fat. OBJECTIVE Our aim was to evaluate the hypothesis that increasing the droplet size of a fat emulsion would attenuate these effects. DESIGN Ten healthy, lean males were studied on 4 separate occasions in single-blind randomized order. Antropyloroduodenal pressures, plasma triglycerides, cholecystokinin, peptide YY, and appetite were measured during 120-min intraduodenal infusions of fat emulsions comprising 3 different droplet sizes: 1) 0.26 microm (LE-0.26), 2) 30 microm (LE-30), and 3) 170 microm (LE-170) in addition to saline (control). Energy intake at a buffet lunch was quantified immediately after the infusions. RESULTS Increasing the droplet size of the lipid emulsion was associated with diminished suppression of antral (r = 0.75, P < 0.01) and duodenal (r = 0.80, P < 0.01) pressure waves and with stimulation of isolated (r = -0.72, P < 0.01) and basal (r = -0.83, P < 0.01) pyloric pressures. Increasing the droplet size was also associated with attenuation of the stimulation of plasma triglycerides (r = -0.73, P < 0.001), cholecystokinin (r = -0.73, P < 0.001), and peptide YY (r = -0.83, P < 0.001) as well as with reductions in the suppression of hunger (r = 0.75, P < 0.01) and energy intake (r = 0.66, P < 0.001). CONCLUSIONS The acute effects of intraduodenal fat emulsions on gastrointestinal function and appetite are dependent on fat droplet size. These observations have implications for the design of functional foods to maximize effects on those gut functions that are involved in the suppression of appetite.

Do ketogenic diets really suppress appetite? A systematic review and meta-analysis.

Very‐low‐energy diets (VLEDs) and ketogenic low‐carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta‐analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate‐containing foods into the diet.

Pooled-data analysis identifies pyloric pressures and plasma cholecystokinin concentrations as major determinants of acute energy intake in healthy, lean men

BACKGROUND The interaction of nutrients with the small intestine modulates gastropyloroduodenal motility, stimulates the release of gut hormones, and suppresses appetite and energy intake. OBJECTIVE We evaluated which, if any, of these variables are independent determinants of acute energy intake in healthy, lean men. DESIGN We pooled data from 8 published studies that involved a total of 67 healthy, lean men in whom antropyloroduodenal pressures, gastrointestinal hormones, and perceptions were measured during intraduodenal nutrient or intravenous hormone infusions. In all of the studies, the energy intake at a buffet lunch was quantified immediately after the infusions. To select specific motor, hormone, or perception variables for inclusion in a multivariable mixed-effects model for determination of independent predictors of energy intake, we assessed all variables for collinearity and determined within-subject correlations between energy intake and these variables by using bivariate analyses adjusted for repeated measures. RESULTS Although correlations were shown between energy intake and antropyloroduodenal pressures, plasma hormone concentrations, and gastrointestinal perceptions, only the peak number of isolated pyloric-pressure waves, peak plasma cholecystokinin concentration, and area under the curve of nausea were identified as independent predictors of energy intake (all P < 0.05), so that increases of 1 pressure wave, 1 pmol/L, and 1 mm . min were associated with reductions in energy intake of approximately 36, approximately 88, and approximately 0.4, respectively. CONCLUSION We identified specific changes in gastrointestinal motor and hormone functions (ie, stimulation of pyloric pressures and plasma cholecystokinin) and nausea that are associated with the suppression of acute energy intake.

Gastric emptying, mouth-to-cecum transit, and glycemic, insulin, incretin, and energy intake responses to a mixed-nutrient liquid in lean, overweight, and obese males

Observations relating to the impact of obesity on gastric emptying (GE) and the secretion of gut hormones are inconsistent, probably because of a lack of studies in which GE, gastrointestinal hormone release, and energy intake (EI) have been evaluated concurrently with previous patterns of nutrient intake. GE is known to be a major determinant of postprandial glycemia and incretin secretion in health and type 2 diabetes. The aims of this study were to determine the effects of a mixed-nutrient drink on GE, oro-cecal transit, blood glucose, insulin and incretin concentrations and EI, and the relationship between the glycemic response to the drink with GE in lean, overweight, and obese subjects. Twenty lean, 20 overweight, and 20 obese males had measurements of GE, oro-cecal transit, and blood glucose, insulin, GLP-1, and GIP concentrations for 5 h after ingestion of a mixed-nutrient drink (500 ml, 532 kcal); EI at a subsequent buffet lunch was determined. Habitual EI was also quantified. Glycemic and insulinemic responses to the drink were greater in the obese (both P < 0.05) when compared with both lean and overweight, with no significant differences in GE, intragastric distribution, oro-cecal transit, incretins, or EI (buffet lunch or habitual) between groups. The magnitude of the rise in blood glucose after the drink was greater when GE was relatively more rapid (r = -0.55, P < 0.05). In conclusion, in the absence of differences in habitual EI, both GE and incretin hormones are unaffected in the obese despite greater glucose and insulin responses, and GE is a determinant of postprandial glycemia.

Effects of varying combinations of intraduodenal lipid and carbohydrate on antropyloroduodenal motility, hormone release, and appetite in healthy males

Intraduodenal infusions of both lipid and glucose modulate antropyloroduodenal motility and stimulate plasma CCK, with lipid being more potent than glucose. Both stimulate glucagon-like peptide-1, but only lipid stimulates peptide YY (PYY), while only glucose raises blood glucose and stimulates insulin. When administered in combination, lipid and carbohydrate may, thus, have additive effects on energy intake. However, elevated blood glucose levels do not suppress energy intake, and the effect of insulin is controversial. We hypothesized that increasing the ratio of maltodextrin, a complex carbohydrate, relative to lipid would be associated with a reduction in effects on antropyloroduodenal pressures, gut hormones, appetite, and energy intake, when compared with lipid alone. Ten healthy males were studied on three occasions in double-blind, randomized order. Antropyloroduodenal pressures, plasma CCK, PYY and insulin, blood glucose, and appetite were measured during 90-min intraduodenal infusions of 1) 3 kcal/min lipid (L3), 2) 2 kcal/min lipid and 1 kcal/min maltodextrin (L2/CHO1), or 3) 1 kcal/min lipid and 2 kcal/min maltodextrin (L1/CHO2). Energy intake at a buffet lunch consumed immediately after the infusion was quantified. Reducing the lipid (thus, increasing the carbohydrate) content of the infusion was associated with reduced stimulation of basal pyloric pressures (r = 0.76, P < 0.01), plasma CCK (r = 0.66, P < 0.01), and PYY (r = 0.98, P < 0.001), and reduced suppression of antral (r = -0.64, P < 0.05) and duodenal (r = -0.69, P < 0.05) pressure waves, desire-to-eat (r = -0.8, P < 0.001), and energy intake (r = 0.74, P < 0.01), with no differences in phasic (isolated) pyloric pressures. In conclusion, in healthy males, intraduodenal lipid is a more potent modulator of gut function, associated with greater suppression of energy intake, when compared with isocaloric combinations of lipid and maltodextrin.

Changes in body weight and blood pressure: paradoxical outcome events in overweight and obese subjects with cardiovascular disease

Background/Objectives:The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in body weight and blood pressure, and the impact of these changes on subsequent cardiovascular outcome events.Subjects/Methods:A total of 9804 male and female subjects, aged 55 years or older, with a body mass index of 27–45 kg m–2 were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor (hypertension, dyslipidemia, current smoking or diabetic nephropathy) to assess cardiovascular outcomes. Post hoc subgroup analyses of weight change (categories) and blood pressure were performed overall and by treatment group (6-week sibutramine followed by randomized placebo or continued sibutramine). The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models with factors for treatment, subgroups and interactions.Results:During the initial 6-week sibutramine treatment period, systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects (−8.1±10.5 mm Hg with <5 kg weight loss to −10.8±11.0 mm Hg with ⩾5 kg weight loss). The highest POE incidence occurred mainly in groups with increases in both weight and blood pressure. However, with long-term sibutramine treatment, a markedly lower blood pressure tended to increase POEs.Conclusion:Modest weight loss and modest lower blood pressure each reduced the incidence of cardiovascular events, as expected. However, the combination of early marked weight loss and rapid blood pressure reduction seems to be harmful in this obese elderly cardiovascular diseased population.

Effects of acute and longer-term dietary restriction on upper gut motility, hormone, appetite, and energy-intake responses to duodenal lipid in lean and obese men

BACKGROUND A 4-d 70% energy restriction enhances gastrointestinal sensitivity to nutrients associated with enhanced energy-intake suppression by lipid. To our knowledge, it is unknown whether these changes occur with 30% energy restriction and are sustained in the longer term. OBJECTIVES We hypothesized that 1) a 4-d 30% energy restriction would enhance effects of intraduodenal lipid on gastrointestinal motility, gut hormones, appetite, and energy intake in lean and obese men and 2) a 12-wk energy restriction associated with weight loss would diminish effects of acute energy restriction on responses to lipid in in obese men. DESIGN Twelve obese males were studied before (day 0) and after 4 d (day 5), 4 wk (week 4), and 12 wk (week 12), and 12 lean males were studied before and after 4 d of consumption of a 30% energy-restricted diet. On each study day, antropyloroduodenal pressures, gut hormones, and appetite during a 120-min (2.86-kcal/min) intraduodenal lipid infusion and energy intake at a buffet lunch were measured. RESULTS On day 5, fasting cholecystokinin was less, and ghrelin was higher, in lean (P < 0.05) but not obese men, and lipid-stimulated cholecystokinin and peptide YY and the desire to eat were greater in both groups (P < 0.05), with no differences in energy intakes compared with on day 0. In obese men, a 12-wk energy restriction led to weight loss (9.7 ± 0.7 kg). Lipid-induced basal pyloric pressures (BPPs), peptide YY, and the desire to eat were greater (P < 0.05), whereas the amount eaten was less (P < 0.05), at weeks 4 and 12 compared with day 0. CONCLUSIONS A 4-d 30% energy restriction modestly affects responses to intraduodenal lipid in health and obesity but not energy intake, whereas a 12-wk energy restriction, associated with weight-loss, enhances lipid-induced BPP and peptide YY and reduces food intake, suggesting that energy restriction increases gastrointestinal sensitivity to lipid. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as 12609000943246.

Effects of acute dietary restriction on gut motor, hormone and energy intake responses to duodenal fat in obese men

Background:Previous patterns of energy intake influence gastrointestinal function and appetite, probably reflecting changes in small-intestinal nutrient-mediated feedback. Obese individuals consume more fat and may be less sensitive to its gastrointestinal and appetite-suppressant effects than lean individuals.Objective:To evaluate the hypothesis that, in obese individuals, the effects of duodenal fat on gastrointestinal motor and hormone function, and appetite would be enhanced by a short period on a very-low-calorie diet (VLCD).Methods:Eight obese men (body mass index 34±0.6 kg m−2) were studied on two occasions, before (V1), and immediately after (V2), a 4-day VLCD. On both occasions, antropyloroduodenal motility, plasma cholecystokinin (CCK), peptide-YY (PYY) and ghrelin concentrations, and appetite perceptions were measured during a 120-min intraduodenal fat infusion (2.86 kcal min−1). Immediately afterwards, energy intake was quantified.Results:During V2, basal pyloric pressure and the number and amplitude of isolated pyloric pressure waves (PWs) were greater, whereas the number of antral and duodenal PWs was less, compared with V1 (all P<0.05). Moreover, during V2, baseline ghrelin concentration was higher; the stimulation of PYY and suppression of ghrelin by lipid were greater, with no difference in CCK concentration; and hunger and energy intake (kJ; V1: 4378±691, V2: 3634±700) were less (all P<0.05), compared with V1.Conclusions:In obese males, the effects of small-intestinal lipid on gastrointestinal motility and some hormone responses and appetite are enhanced after a 4-day VLCD.