Regulation Of Energy Intake Research Articles

Is your brain to blame for weight regain?

Obesity is a serious and growing public health problem in the United States and the world. While weight loss is associated with significant benefits in obesity-related co-morbidities, successful long-term weight loss maintenance is extremely difficult. This limited success is primarily due to biologic mechanisms that clearly favor weight regain. The weight-reduced state is associated with not only reductions in energy expenditure and changes in substrate metabolism but also in increased energy intake. Measures of appetite (increased hunger, reduced satiety) clearly change with weight loss. These changes in appetite may be mediated by alterations of peripheral appetite-related signals, such as leptin and meal-related gut peptides, promoting energy intake. Furthermore, significant changes in the neuronal response to food-related cues in the weight-reduced state have also been shown, stressing the importance of the interactions between homeostatic and non-homeostatic regulation of energy intake. In summary, the weight-reduced state is clearly associated with a dysregulation of energy balance regulation, resulting in a milieu promoting weight regain, and thus being one of the major obstacles of treating obesity and reducing its comorbidities. This paper will review the adaptations in the central regulation of energy intake that occur after weight-loss or in the weight-reduce state in humans, including changes in peripheral appetite-related signals and neuroimaging studies examining the brain's response to weight loss.

Ghrelin and PYY3−36 in gastrectomized and vagotomized patients: relations with appetite, energy intake and resting energy expenditure

Reduced food intake, appetite loss and alteration of ghrelin and PYY(3-36) secretion have been suggested to have a function in the loss of body weight commonly observed after gastrectomy. The objective of this study was to investigate the circulating concentrations of ghrelin and PYY(3-36) and their relationships with food intake, appetite and resting energy expenditure (REE) after gastrectomy plus vagotomy. Seven patients with total gastrectomy (TG), 14 with partial gastrectomy (PG) and 10 healthy controls were studied. Habitual food intake and REE was assessed; fasting and postprandial plasma total ghrelin, PYY(3-36) concentrations and appetite ratings were determined after ingestion of a liquid test meal. Differently from PG and controls, fasting ghrelin correlated with REE, and a higher energy intake was observed in the TG group. Fasting plasma ghrelin concentrations were lower in TG compared with controls, and no ghrelin response to the meal was observed in either PG or TG. Fasting plasma PYY(3-36) concentrations were not different among the groups. There was an early and exaggerated postprandial rise in PYY(3-36) levels in both PG and TG groups, but not in controls. No effect of ghrelin or PYY(3-36) concentrations was observed on hunger, prospective consumption or fullness ratings. Total ghrelin and PYY(3-36) do not seem to be involved with appetite or energy intake regulation after gastrectomy plus vagotomy. Ghrelin secreted by sources other than stomach is likely to have a function in the long-term regulation of body weight after TG.

The neurohormonal regulation of energy intake in relation to bariatric surgery for obesity

Obesity has reached pandemic proportions, with bariatric surgery representing the only currently available treatment demonstrating long-term effectiveness. Over 200,000 bariatric procedures are performed each year in the US alone. Given the reliable and singular success of bariatric procedures, increased attention is being paid to identifying the accompanying neurohormonal changes that may contribute to the resulting decrease in energy intake. Numerous investigations of postsurgical changes in gut peptides have been conducted, suggesting greater alterations in endocrine function in combination restrictive and malabsorptive procedures (e.g., Roux-en-Y gastric bypass) as compared to purely restrictive procedures (e.g., gastric banding), which may contribute to the increased effectiveness of combination procedures. However, very few studies have been performed and relatively little is known about changes in neural activation that may result from bariatric procedures, which likely interact with changes in gut peptides to influence postsurgical caloric intake. This review provides a background in the neurohormonal regulation of energy intake and discusses how differing forms of bariatric surgery may affect the neurohormonal network, with emphasis on Roux-en-Y gastric bypass, the most commonly performed procedure worldwide. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.

A low-fat liquid diet increases protein accretion and alters cellular signaling for protein synthesis in 10-day-old pigs1

Previous research showed that neonatal pigs respond to decreases in energy density of liquid diets with increased feed intake, resulting in similar performance to pigs fed a more energy-dense diet. The objective of this experiment was to determine whether a high- (25%, HF) or low-fat (2%, LF) liquid diet would affect nutrient accretion rate and select proteins involved in energy homeostasis and protein synthesis in early weaned pigs. Ninety-six pigs, with an initial BW of 3,637 +/- 85 g, were weaned from the sow at 10 d of age and utilized in a randomized complete block design. Pigs were blocked by BW and then assigned to pens (8 pigs/pen). Diets were formulated to provide a constant AA:ME ratio and were fed for 10 d. Pigs were killed at 10, 15, and 20 d of age, at which time blood and LM were collected, and carcasses were prepared for body composition analysis. Blood was analyzed for plasma urea nitrogen (PUN) and NEFA. Longissimus dorsi was analyzed via western immunoblot for mammalian target of rapamycin (mTOR) and adenosine 5' monophosphate-activated protein kinase (AMPK) phosphorylation. Pigs gained 347 +/- 11 g/d, which resulted in an ending BW of 6,858 +/- 135 g, regardless of dietary treatment (P > 0.49). Pigs fed the LF diet consumed 25% more milk than pigs fed the HF diet (2,853 +/- 86 vs. 2,269 +/- 79 g dry feed.pen(-1).d(-1); P < 0.01), which resulted in similar calculated ME intakes between dietary treatments (9.9 +/- 0.2 vs. 10.5 +/- 0.2 Mcal.pen(-1).d(-1); P > 0.5). Feed conversion (G:F) was 24% greater in HF-fed compared with LF-fed pigs (P < 0.01). Circulating NEFA (40 +/- 14 vs. 138 +/- 21 microEq/L; P < 0.01) and PUN (3.0 +/- 0.6 vs. 17.7 +/- 0.8 mM; P < 0.01) concentrations were less in LF pigs compared with HF pigs after 10 d of dietary treatments. Pigs consuming the LF diet had a 21% increase in protein accretion (50.5 +/- 2.8 vs. 61.2 +/- 2.8 g/d; P < 0.04) and a 71% reduced lipid accretion rate (28.8 +/- 2.0 vs. 8.3 +/- 2.3 g/d; P < 0.001). Phosphorylation of AMPK was 29% less (P < 0.03) in LF pigs compared with HF pigs, whereas mTOR phosphorylation was increased by 37% in LF pigs (P < 0.01). We conclude that feeding a LF liquid diet to pigs weaned from the sow at 10 d of age increases feed intake to regulate energy intake while maintaining growth performance. In addition, 10-d-old pigs consuming a liquid LF diet have increased protein deposition by a mechanism mediated through AMPK and mTOR.

Intake during repeated exposure to low- and high-energy-dense yogurts by different means of consumption

An important question in the regulation of energy intake is whether dietary learning of energy content depends on the food's characteristics, such as texture. Texture might affect the duration of sensory exposure and eating rate. The objective was to investigate whether a long sensory exposure, due to differences in means of consumption and in viscosity, enhances learned associations between sensory signals and metabolic consequences and hence facilitates energy intake compensation. A total of 105 healthy young adults with a mean (+/-SD) age of 22 +/- 3 y and a body mass index (in kg/m(2)) of 21.6 +/- 1.7 participated in a parallel intervention in 3 groups: liquid yogurt with a straw (liquid/straw; n = 34), liquid yogurt with a spoon (liquid/spoon; n = 36), or semisolid yogurt with a spoon (semisolid/spoon; n = 35). Novel flavored yogurts were offered ad libitum for breakfast in 2 energy densities: low ( approximately 215 kJ/100 g) and high ( approximately 600 kJ/100 g). Subjects were repeatedly exposed to the yogurt products (10 times), and yogurt intake was measured. Intakes (P = 0.01) and eating rates (P = 0.01) were highest in the liquid/straw group. Average intakes over 10 exposures were 575 +/- 260 g for liquid/straw, 475 +/- 192 g for liquid/spoon, and 470 +/- 223 g for semisolid/spoon; average eating rates were 132 +/- 83 g/min for liquid/straw, 106 +/- 53 g/min for liquid/spoon, and 105 +/- 88 g/min for semisolid/spoon. No significant interaction for intake between intervention group, energy density, and repeated exposure was observed, and intakes of the low- and high-energy-dense yogurts did not change over time in any of the intervention groups. We observed no energy intake compensation after repeated exposure to yogurt products. Differences in ad libitum yogurt intake could be explained by eating rate, which was affected by the different means of consumption. This trial was registered with the Dutch trial registration at http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1853 as NTR1853.

Regulation of ghrelin production by gastric mTOR signaling

The role of gastric mTOR signaling in ghrelin production and food intake was examined in this study. Here we showed the reciprocal relationship of gastric mTOR signaling and ghrelin during changes in energy status. mTOR activity was down‐regulated, while gastric preproghrelin and circulating total and acyl ghrelin were increased by fasting. In db/db mice, gastric mTOR signaling was enhanced, whereas gastric preproghrelin and circulating total anc acyl ghrelin were decreased. Inhibition of the gastric mTOR signaling by rapamycin stimulated the expression of gastric preproghrelin and ghrelin mRNA, increased the plasma total and acyl ghrelin in both wildtype and db/db mice. Activation of the gastric mTOR signaling by L‐leucine decreased the expression of gastric preproghrelin and the level of plasma total and acyl ghrelin. Ghrelin receptor antagonist D‐Lys3‐growth hormone releasing peptide‐6 abolished the rapamycin‐induced increment in food intake despite that plasma ghrelin remained elevated. mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of energy intake through ghrelin.

The addition of a protein-rich breakfast and its effects on acute appetite control and food intake in ‘breakfast-skipping’ adolescents

Breakfast skipping (BS) is closely associated with overeating (in the evening), weight gain and obesity. It is unclear whether the addition of breakfast, with emphasis on dietary protein, leads to better appetite and energy intake regulation in adolescents. The purpose of the study was to examine the impact of addition of a normal-protein (PN) breakfast vs protein-rich (PR) breakfast on appetite and food intake in 'breakfast-skipping' adolescents. A total of 13 adolescents (age 14.3+/-0.3 years; body mass index percentile 79+/-4 percentile; skipped breakfast 5+/-1 x per week) randomly completed 3 testing days that included a PN (18+/-1 g protein), PR (48+/-2 g protein) or BS. Breakfast was 24% of estimated daily energy needs. Appetite, satiety and hormonal responses were collected over 5 h followed by an ad libitum lunch and 24-h food intake assessments. Perceived appetite was not different following PN vs BS; PR led to greater reductions vs BS (P<0.01) and PN (P<0.001). Fullness was greater following both breakfast meals vs BS (P<0.01) but was not different between meals. Ghrelin was not different among treatments. Greater PYY concentrations were observed following both breakfast meals vs BS (P<0.01) but was not different between meals. Lunch energy intake was not different following PN vs BS; PR led to fewer kcal consumed vs BS (P<0.01) and PN (P<0.005). Daily food intake was not different among treatments. Breakfast led to increased satiety through increased fullness and PYY concentrations in 'breakfast skipping' adolescents. A breakfast rich in dietary protein provides additional benefits through reductions in appetite and energy intake. These findings suggest that the addition of a protein-rich breakfast might be an effective strategy to improve appetite control in young people.

The effect of fibre amount, energy level and viscosity of beverages containing oat fibre supplement on perceived satiety

Background: Soluble fibre has been proposed to suppress appetite-related perceptions and it could thus contribute favourably to the regulation of energy intake and the increasing obesity problem.Objective: To investigate the effect of an oat ingredient rich in β-glucan on perceived satiety at different dietary fibre (DF) concentrations, energy levels and viscosity levels.Design: A total of 29 healthy volunteers, age 19–39, mean BMI 23.2 kg/m2 participated in this study. Measurement of subjective perceptions (satiety, fullness, hunger, desire to eat something/the sample food and thirst) was performed during a 180-min period after ingestion of the sample. There were altogether six samples: two beverages without fibre at energy levels 700 and 1,400 kJ; two beverages containing 5 or 10 g oat DF (2.5 and 5 g oat β-glucan, respectively) at energy level 700 kJ, one beverage containing 10 g oat DF/1,400 kJ and one beverage containing 10 g enzymatically treated oat DF with low viscosity at energy level 700 kJ. Each beverage portion weighted 300 g. The order of the samples was randomised for each subject and evaluated during six separate days. The results are reported in three sets of samples: ‘fibre’, ‘energy’ and ‘viscosity’.Results: In the fibre set, the beverages containing 5 or 10 g of fibre had a larger area under curve (AUC) for perceived satiety and smaller AUC for hunger compared to the beverage without fibre, but no significant dose–response relationship was detected. Increasing the energy content from 700 to 1,400 kJ in the energy set did not affect the satiety-related perceptions. In the viscosity set, the beverage with low-viscosity β-glucan increased satiety-related perceptions from no fibre containing beverage, but less compared to the beverage with the same amount of fibre and higher viscosity.Conclusions: Addition of an oat ingredient rich in β-glucan and high viscosity of beverages enhance post-meal satiety induced by beverages. The effect was, however, not related to the amount of ingested fibre or energy.

Hypothalamic FTO is associated with the regulation of energy intake not feeding reward

BackgroundPolymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH) was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal.ResultsDeprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin.ConclusionWe conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism.

Comparable effects of moderate intensity exercise on changes in anorectic gut hormone levels and energy intake to high intensity exercise

There is growing interest in the effects of exercise on plasma gut hormone levels and subsequent energy intake (EI) but the effects of mode and exercise intensity on anorectic hormone profiles on subsequent EI remain to be elucidated. We aimed to investigate whether circulating peptide YY(3-36) (PYY(3-36)) and glucagon-like peptide-1 (GLP-1 or GCG as listed in the HUGO Database) levels depend on exercise intensity, which could affect subsequent EI. Ten young male subjects (mean+/-s.d., age: 23.4+/-4.3 years, body mass index: 22.5+/-1.0 kg/m(2), and maximum oxygen uptake (VO(2 max)): 45.9+/-8.5 ml/kg per min) received a standardized breakfast, which was followed by constant cycling exercise at 75% VO(2 max) (high intensity session), 50% VO(2 max) (moderate intensity session), or rest (resting session) for 30 min. At lunch, a test meal was presented, and EI was calculated. Blood samples were obtained during three sessions for measurements of glucose, insulin, PYY(3-36), and GLP-1, which includes GLP-1 (7-36) amide and GLP-1 (9-36) amide. Increases in blood PYY(3-36) levels were dependent on the exercise intensity (effect of session: P<0.001 by two-way ANOVA), whereas those in GLP-1 levels were similar between two different exercise sessions. Of note, increase in area under the curve values for GLP-1 levels was negatively correlated with decrease in the EI in each exercise session (high: P<0.001, moderate: P=0.002). The present findings raise the possibility that each gut hormone exhibits its specific blood kinetics in response to two different intensities of exercise stimuli and might play differential roles in regulation of EI after exercise.

A sideway glance: a new role for endoplasmic reticulum chemical chaperones as leptin sensitizers

The epidemic surge in the prevalence of obesity is one of the most serious public health problem confronting the western societies. Among the adult population in the USA, 65% is overweight and more than 30% is obese and the picture in Europe is becoming very similar. There has also been an increase in the obese pediatric population with one out of three Americans born in the year 2000 expected to suffer from the complications of obesity like hypertension, type-2 diabetes and arteriosclerosis later in life [1]. However, the mechanisms behind obesity are still controversial. Obesity is usually considered as merely lifestyle disease caused by overeating and/or decreased physical activity. Although these factors have obviously great influence on weight gain, results of many investigations strongly indicate that hereditary factors could be of equal importance for the development of obesity and of its complications. Studies conducted on twins and on adoptive children show that most familial aggregation of obesity is due to genetic influence rather than to family environment. Interestingly, even in obese subjects, the weight gain throughout life is very small compared to the amount of energy ingested; and a weight gain of about 15 kg, compared to about 50 million cal (18 tons of food) ingested in lifetime which means that the regulation of the fat depots would be off by only 0.02%. This regulation must be extremely precise and the refined control mechanism is at least in part under genetic control. It has been proposed that secondary to overeating, the storage of additional fat will send signals to the brain informing that the body is overweight, inducing the subject to eat less and to burn more calories [2]. A major player in regulating energy intake and energy expenditure is leptin. This hormone protein was discovered as the product of the ob gene. Mice ob/ob were obese and had type-2 diabetes, due to the segregation of a single genetic locus containing the mutation. The gene is expressed only in fat cells, white and brown, and encodes a 167 amino acid-long protein, leptin. Leptin is secreted after its synthesis and functions as part of a lipostatic signaling pathway that modulates energy balance by central and peripheric effects. When fat cells increase in number and size, greater amounts of leptin are secreted into the circulation in order to maintain body weight and energy depots in equilibrium. Hypothalamus, with its central role in the regulation of hunger and satiety, is most probably the major target for leptin [3]. Treatment with recombinant leptin has resulted in a marked weight reduction in obese animals with ob gene mutations as well as in normal mice. According to its function it was found also that mutations in the Ob receptor gene resulted in marked obesity in rodents.

Systematic gene expression profile of hypothalamus in calorie-restricted mice implicates the involvement of mTOR signaling in neuroprotective activity

Calorie restriction (CR) delays aging and onset of age-related diseases in a variety of organisms from yeast to mammals. However, the molecular mechanism underlying the CR effect remains to be elucidated. It is well known that the hypothalamus is an important component of the brain neuroendocrine system for the regulation of the aging process. In this report, we have systematically examined the gene expression profiles of hypothalami from 5-, 12-, 19- and 24-month-old mice fed ad libitum or subjected to CR since weaning. Our results demonstrated that CR significantly altered the expression level of 490 genes in an age-dependent manner, with the greatest impact at middle age. Classification based on functional analysis indicated that a large number of these genes were involved in brain development and neurogenesis, including genes involved in Wingless (Wnt) and Notch signaling pathways. In addition, the expression levels of numerous genes involved in the stress and inflammatory responses, as well as apoptosis, were affected by CR. Interestingly, we found that a number of genes involved in the stress response and apoptosis were down-regulated in early but up-regulated in late stage CR. The most notable finding was that CR altered the expression of genes associated with the mammalian target of the rapamycin (mTOR) nutrient sensing pathway, which has recently been shown to be involved in the regulation of energy intake and aging. By applying rapamycin, a specific pharmacological inhibitor of mTOR signaling, we found that the inhibition of mTOR could significantly prevent neuronal apoptosis induced by Paraquat. Taken together, our results provided not only a systematic expression profile of the hypothalamic response to CR, but also revealed the linkage between CR and mTOR signaling in the neuroprotection in mice.

The Effects of Overfeeding on the Neuronal Response to Visual Food Cues in Thin and Reduced-Obese Individuals

BackgroundThe regulation of energy intake is a complex process involving the integration of homeostatic signals and both internal and external sensory inputs. The objective of this study was to examine the effects of short-term overfeeding on the neuronal response to food-related visual stimuli in individuals prone and resistant to weight gain.Methodology/Principal Findings22 thin and 19 reduced-obese (RO) individuals were studied. Functional magnetic resonance imaging (fMRI) was performed in the fasted state after two days of eucaloric energy intake and after two days of 30% overfeeding in a counterbalanced design. fMRI was performed while subjects viewed images of foods of high hedonic value and neutral non-food objects. In the eucaloric state, food as compared to non-food images elicited significantly greater activation of insula and inferior visual cortex in thin as compared to RO individuals. Two days of overfeeding led to significant attenuation of not only insula and visual cortex responses but also of hypothalamus response in thin as compared to RO individuals.Conclusions/SignificanceThese findings emphasize the important role of food-related visual cues in ingestive behavior and suggest that there are important phenotypic differences in the interactions between external visual sensory inputs, energy balance status, and brain regions involved in the regulation of energy intake. Furthermore, alterations in the neuronal response to food cues may relate to the propensity to gain weight.

Leptin regulates expression of Agouti-related protein in hypothalamus:recent progress

Hypotha is the center of energy homeostasis in the organism.The central step of its endocrinology regulation network is that it can receive the leptin signal provided by peripheral adipose tissues,and subsequently modulate the expression of Agouti-related protein(AgRP) and proopiomelanocortin(POMC),maintaining energy homeostasis by regulating energy intake and consumption.Transcription factors FoxO1 and STAT3(signal transducer and activator of transcription 3) are key molecules in leptin-mediated transcriptional regulation of AgRP;they directly participate in the regulation of energy homeostasis.FoxO1 can enhance AgRP expression and activated STAT3 can inhibit AgRP expression.Leptin can modulate AgRP and energy homeostasis through inhibiting FoxO1 activity and activating STAT3.The article reviews the regulatory mechanism of leptin upon AgRP.

The management of obesity

AbstractThe prevalence and incidence of obesity is rising as current ways of managing obesity are proving to be ineffective. The preferred approach is to induce an energy deficit by decreasing energy intake through a low calorie diet and increasing energy expenditure through exercise. In order to provoke body weight loss the changes in lifestyle that this approach involves have to be sustained and while some individuals have the motivation to do this the vast majority of the population has not. Very low calorie diets are ineffective as the body adapts to them by lowering energy expenditure and altering the macronutrient composition of low calorie diets has no additional effect. The anti‐obesity drugs orlistat, sibutramine and rimonabant can provoke body weight loss but all suffer from side effects. However, the explosion in our understanding of the factors that regulate energy intake is likely to lead to the development of more effective drugs with fewer side effects. Bariatric or weight reducing surgery is highly effective at provoking body weight loss but there are obvious barriers to its widespread use.

The regulation of energy balance

AbstractStorage of excess energy as body fat happens when the human body loses its ability to match rates of energy intake to rates of energy expenditure. Studies of genetically obese mice and their human counterparts have revealed the importance of leptin: a hormone secreted by body fat which acts on the hypothalamus to inhibit energy intake and stimulate energy expenditure. Defects in the ability of leptin to inhibit energy intake are responsible for all the human congenital obesity syndromes so far identified. Leptin also shifts energy production away from carbohydrate oxidation and towards fat oxidation. A wide range of hormones secreted by the gastrointestinal system also regulate energy intake including ghrelin which stimulates it and cholecystokinin which inhibits it. The fact that energy intake can be genetically determined means that the drive to eat is not necessarily a voluntary act and this has implications for the success of strategies aimed at managing obesity.

Satiation, satiety and their effects on eating behaviour

Satiation, satiety and their effects on eating behaviour

Gastric Mammalian Target of Rapamycin Signaling Regulates Ghrelin Production and Food Intake

Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. Mammalian target of rapamycin (mTOR) is an intracellular fuel sensor critical for cellular energy homeostasis. Here we showed the reciprocal relationship of gastric mTOR signaling and ghrelin during changes in energy status. mTOR activity was down-regulated, whereas gastric preproghrelin and circulating ghrelin were increased by fasting. In db/db mice, gastric mTOR signaling was enhanced, whereas gastric preproghrelin and circulating ghrelin were decreased. Inhibition of the gastric mTOR signaling by rapamycin stimulated the expression of gastric preproghrelin and ghrelin mRNA and increased plasma ghrelin in both wild-type and db/db mice. Activation of the gastric mTOR signaling by l-leucine decreased the expression of gastric preproghrelin and the level of plasma ghrelin. Overexpression of mTOR attenuated ghrelin promoter activity, whereas inhibition of mTOR activity by overexpression of TSC1 or TSC2 increased its activity. Ghrelin receptor antagonist d-Lys-3-GH-releasing peptide-6 abolished the rapamycin-induced increment in food intake despite that plasma ghrelin remained elevated. mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of energy intake through ghrelin.

HYPOTHALAMIC regulation of energy intake.

HYPOTHALAMIC regulation of energy intake.

Cholecystokinin and Ghrelin are blunted in overweight women compared to normal weight women after protein preloads.

CCK and ghrelin have opposing roles in appetite regulation and are influenced by incoming nutrients. Protein induces satiety, although its potency varies by source. Whether protein provides equivalent satiety independent of body fatness has not been well characterized bio‐behaviorally. In a randomized crossover design, 10 normal weight (NW, BMI 22.06 ± 1.56) and 10 overweight (OW, BMI 31.82 ± 2.97) unrestrained women (23.65y ± 6) consumed 1 of 4 test beverage preloads (2MJ) containing 40g dairy protein isolates; milk protein (MPI), whey (WPI), and casein (CPI), or no protein control (NPC). Cholecystokinin (CCK), ghrelin, insulin, glucose and subjective satiety (SS; by VAS) were assessed over 5 h at defined intervals post preload. Preload (p&lt;0.006) and time (p&lt;0.0001) affected CCK, insulin, glucose, and SS (n=16 of 20). Preload by BMI interactions were observed for CCK (p=0.02), ghrelin, (p&lt;0.004), glucose (p= 0.01), hunger (p=0.0001) and fullness (p=0.005). The CCK response to preloads was blunted in OW vs NW. Ghrelin was blunted in OW vs NW after CPI and MPI. Insulin was higher in OW vs NW (p=0.04); and as a group (n=16), WPI and CPI induced higher insulin than NPC or MPI. Glucose was higher after NPC vs protein preloads (p&lt;0.001). Hunger and fullness corresponded with CCK and ghrelin responses to preloads suggesting OW people are receiving inadequate signaling to regulate energy intake. Funding provided by USDA NRI.