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Intranasal insulin enhances brain functional connectivity mediating the relationship between adiposity and subjective feeling of hunger.
Kullmann, S, Heni, M, Veit, R, Scheffler, K, Machann, J, Häring, HU, Fritsche, A, Preissl, H
Scientific reports. 2017;(1):1627
Abstract
Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.
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Feed-forward neural network model for hunger and satiety related VAS score prediction.
Krishnan, S, Hendriks, HF, Hartvigsen, ML, de Graaf, AA
Theoretical biology & medical modelling. 2016;(1):17
Abstract
BACKGROUND An artificial neural network approach was chosen to model the outcome of the complex signaling pathways in the gastro-intestinal tract and other peripheral organs that eventually produce the satiety feeling in the brain upon feeding. METHODS A multilayer feed-forward neural network was trained with sets of experimental data relating concentration-time courses of plasma satiety hormones to Visual Analog Scales (VAS) scores. The network successfully predicted VAS responses from sets of satiety hormone data obtained in experiments using different food compositions. RESULTS The correlation coefficients for the predicted VAS responses for test sets having i) a full set of three satiety hormones, ii) a set of only two satiety hormones, and iii) a set of only one satiety hormone were 0.96, 0.96, and 0.89, respectively. The predicted VAS responses discriminated the satiety effects of high satiating food types from less satiating food types both in orally fed and ileal infused forms. CONCLUSIONS From this application of artificial neural networks, one may conclude that neural network models are very suitable to describe situations where behavior is complex and incompletely understood. However, training data sets that fit the experimental conditions need to be available.
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Food-related odor probes of brain reward circuits during hunger: a pilot FMRI study.
Bragulat, V, Dzemidzic, M, Bruno, C, Cox, CA, Talavage, T, Considine, RV, Kareken, DA
Obesity (Silver Spring, Md.). 2010;(8):1566-71
Abstract
Food aromas can be powerful appetitive cues in the natural environment. Although several studies have examined the cerebral responses to food images, none have used naturalistic food aromas to study obesity. Ten individuals (five normal-weight and five obese) were recruited to undergo 24 h of food deprivation. Subjects were then imaged on a 3T Siemens Trio-Tim scanner (Siemens, Erlangen, Germany) while smelling four food-related odors (FRO; two sweet odors and two fat-related) and four "nonappetitive odors" (NApO; e.g., Douglas fir). Before the imaging session, subjects rated their desire to eat each type of food to determine their most preferred (P-FRO). Across all 10 subjects, P-FRO elicited a greater blood oxygenation level dependent (BOLD) response than the NApO in limbic and reward-related areas, including the bilateral insula and opercular (gustatory) cortex, the anterior and posterior cingulate, and ventral striatum. Obese subjects showed greater activation in the bilateral hippocampus/parahippocampal gyrus, but lean controls showed more activation in the posterior insula. Brain areas activated by food odors are similar to those elicited by cues of addictive substances, such as alcohol. Food odors are highly naturalistic stimuli, and may be effective probes of reward-related networks in the context of hunger and obesity.
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The influence of higher protein intake and greater eating frequency on appetite control in overweight and obese men.
Leidy, HJ, Armstrong, CL, Tang, M, Mattes, RD, Campbell, WW
Obesity (Silver Spring, Md.). 2010;(9):1725-32
Abstract
The purpose of this study was to determine the effects of dietary protein intake and eating frequency on perceived appetite, satiety, and hormonal responses in overweight/obese men. Thirteen men (age 51 +/- 4 years; BMI 31.3 +/- 0.8 kg/m(2)) consumed eucaloric diets containing normal protein (79 +/- 2 g protein/day; 14% of energy intake as protein) or higher protein (138 +/- 3 g protein/day; 25% of energy intake as protein) equally divided among three eating occasions (3-EO; every 4 h) or six eating occasions (6-EO; every 2 h) on four separate days in randomized order. Hunger, fullness, plasma glucose, and hormonal responses were assessed throughout 11 h. No protein x eating frequency interactions were observed for any of the outcomes. Independent of eating frequency, higher protein led to greater daily fullness (P < 0.05) and peptide YY (PYY) concentrations (P < 0.05). In contrast, higher protein led to greater daily ghrelin concentrations (P < 0.05) vs. normal protein. Protein quantity did not influence daily hunger, glucose, or insulin concentrations. Independent of dietary protein, 6-EO led to lower daily fullness (P < 0.05) and PYY concentrations (P < 0.05). The 6-EO also led to lower glucose (P < 0.05) and insulin concentrations (P < 0.05) vs. 3-EO. Although the hunger-related perceived sensations and hormonal responses were conflicting, the fullness-related responses were consistently greater with higher protein intake but lower with increased eating frequency. Collectively, these data suggest that higher protein intake promotes satiety and challenge the concept that increasing the number of eating occasions enhances satiety in overweight and obese men.
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Ghrelin increases hunger and food intake in patients with restricting-type anorexia nervosa: a pilot study.
Hotta, M, Ohwada, R, Akamizu, T, Shibasaki, T, Takano, K, Kangawa, K
Endocrine journal. 2009;(9):1119-28
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Abstract
Ghrelin increases hunger sensation and food intake in various patients with appetite loss. Anorexia nervosa (AN) begins with psychological stress-induced anorexia and some patients cannot increase their food intake partly because of malnutrition-induced gastrointestinal dysfunction. The effects of ghrelin on appetite, food intake and nutritional parameters in anorexia nervosa (AN) patients were examined. Five female restricting- type AN patients (age: 14-35 y; body mass index: 10.2-14.6 kg/m(2)) had persistently complained of gastrointestinal symptoms and failed to increase body weight. They were hospitalized for 26 days (6 days' pretreatment, 14 days' ghrelin-treatment, and 6 days' post-treatment) and received an intravenous infusion of 3 microg/kg ghrelin twice a day. Ghrelin infusion improved epigastric discomfort or constipation in 4 patients, whose hunger scores evaluated by visual analogue scale questionnaires also increased significantly after ghrelin infusion. Daily energy intake during ghrelin infusion increased by 12-36 % compared with the pre-treatment period. Serum levels of total protein and triglyceride as nutritional parameters significantly increased after ghrelin treatment. There were no serious adverse effects including psychological symptoms. We found that ghrelin decreases gastrointestinal symptoms and increases hunger sensation and daily energy intake without serious adverse events in AN patients. Although the present study had major limitations of the lack of a randomized, placebo-controlled group, non-blindness of the investigators and the small number of patients recruited, it would contribute to further investigations for therapeutic potential of ghrelin in AN patients.
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Dual-process action of exercise on appetite control: increase in orexigenic drive but improvement in meal-induced satiety.
King, NA, Caudwell, PP, Hopkins, M, Stubbs, JR, Naslund, E, Blundell, JE
The American journal of clinical nutrition. 2009;(4):921-7
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Abstract
BACKGROUND Exercise could contribute to weight loss by altering the sensitivity of the appetite regulatory system. OBJECTIVE The aim of this study was to assess the effects of 12 wk of mandatory exercise on appetite control. DESIGN Fifty-eight overweight and obese men and women [mean (+/-SD) body mass index (in kg/m(2)) = 31.8 +/- 4.5, age = 39.6 +/- 9.8 y, and maximal oxygen intake = 29.1 +/- 5.7 mL . kg(-1) . min(-1)] completed 12 wk of supervised exercise in the laboratory. The exercise sessions were designed to expend 2500 kcal/wk. Subjective appetite sensations and the satiating efficiency of a fixed breakfast were compared at baseline (week 0) and at week 12. An Electronic Appetite Rating System was used to measure subjective appetite sensations immediately before and after the fixed breakfast in the immediate postprandial period and across the whole day. The satiety quotient of the breakfast was determined by calculating the change in appetite scores relative to the breakfast's energy content. RESULTS Despite large variability, there was a significant reduction in mean body weight (3.2 +/- 3.6 kg), fat mass (3.2 +/- 2.2 kg), and waist circumference (5.0 +/- 3.2 cm) after 12 wk. The analysis showed that a reduction in body weight and body composition was accompanied by an increase in fasting hunger and in average hunger across the day (P < 0.0001). Paradoxically, the immediate and delayed satiety quotient of the breakfast also increased significantly (P < 0.05). CONCLUSIONS These data show that the effect of exercise on appetite regulation involves at least 2 processes: an increase in the overall (orexigenic) drive to eat and a concomitant increase in the satiating efficiency of a fixed meal.
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Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues.
Cummings, DE, Frayo, RS, Marmonier, C, Aubert, R, Chapelot, D
American journal of physiology. Endocrinology and metabolism. 2004;(2):E297-304
Abstract
Ghrelin is an orexigenic hormone that is implicated in meal initiation, in part because circulating levels rise before meals. Because previous human studies have examined subjects fed on known schedules, the observed preprandial ghrelin increases could have been a secondary consequence of meal anticipation. A causal role for ghrelin in meal initiation would be better supported if preprandial increases occurred before spontaneously initiated meals not prompted by external cues. We measured plasma ghrelin levels among human subjects initiating meals voluntarily without cues related to time or food. Samples were drawn every 5 min between a scheduled lunch and a freely requested dinner, and hunger scores were obtained using visual analog scales. Insulin, glucose, fatty acids, leptin, and triglycerides were also measured. Ghrelin levels decreased shortly after the first meal in all subjects. A subsequent preprandial increase occurred over a wide range of intermeal intervals (IMI; 320-425 min) in all but one subject. Hunger scores and ghrelin levels showed similar temporal profiles and similar relative differences in magnitude between lunch and dinner. One subject displayed no preprandial ghrelin increase and was also the only individual whose insulin levels did not return to baseline between meals. This finding, along with a correlation between area-under-the-curve values of ghrelin and insulin, suggests a role for insulin in ghrelin regulation. The preprandial increase of ghrelin levels that we observed among humans initiating meals voluntarily, without time- or food-related cues, and the overlap between these levels and hunger scores are consistent with a role for ghrelin in meal initiation.
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Effects of sibutramine on binge eating, hunger, and fullness in a laboratory human feeding paradigm.
Mitchell, JE, Gosnell, BA, Roerig, JL, de Zwaan, M, Wonderlich, SA, Crosby, RD, Burgard, MA, Wambach, BN
Obesity research. 2003;(5):599-602
Abstract
OBJECTIVE The purpose of this study was to evaluate the effects of sibutramine vs. placebo on binge-eating behavior, hunger, and satiety in patients who had problems with binge eating. RESEARCH METHODS AND PROCEDURES Seven adult subjects who had problems with binge eating (mean age, 42 years) were randomly assigned to receive alternating sibutramine and placebo in a double-blind placebo-controlled crossover study. This involved two 4-week dosing periods separated by a 2-week washout. RESULTS Subjects lost weight on sibutramine but not on placebo. There was a significant difference in the number of kilocalories consumed between the sibutramine and placebo conditions, with a significant reduction of intake during binge-eating episodes on sibutramine. DISCUSSION Sibutramine suppresses intake during binge-eating episodes. This effect is demonstrable in a human feeding laboratory paradigm.
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Involvement of human amygdala and orbitofrontal cortex in hunger-enhanced memory for food stimuli.
Morris, JS, Dolan, RJ
The Journal of neuroscience : the official journal of the Society for Neuroscience. 2001;(14):5304-10
Abstract
We used positron emission tomography to measure regional cerebral blood flow (rCBF) in 10 healthy volunteers performing a recognition memory task with food and non-food items. The biological salience of the food stimuli was manipulated by requiring subjects to fast before the experiment and eat to satiation at fixed time points during scanning. All subjects showed enhanced recognition of food stimuli (relative to non-food) in the fasting state. Satiation significantly reduced the memory advantage for food. Left amygdala rCBF covaried positively with recognition memory for food items, whereas rCBF in right anterior orbitofrontal cortex covaried with overall memory performance. Right posterior orbitofrontal rCBF covaried positively with hunger ratings during presentation of food items. Regression analysis of the neuroimaging data revealed that left amygdala and right lateral orbitofrontal rCBF covaried as a function of stimulus category (i.e., food vs non-food). These results indicate the involvement of amygdala and discrete regions of orbitofrontal cortex in the integration of perceptual (food), motivational (hunger), and cognitive (memory) processes in the human brain.