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Beneficial effects of leptin substitution on impaired eating behavior in lipodystrophy are sustained beyond 150 weeks of treatment.
Püschel, J, Miehle, K, Müller, K, Villringer, A, Stumvoll, M, Fasshauer, M, Schlögl, H
Cytokine. 2019;:400-404
Abstract
AIM: Metreleptin treatment in lipodystrophy patients improves eating behavior with increased satiety and reduced hunger. However, no data are available whether effects are maintained beyond 52 weeks of treatment. METHODS A prospective study with measurements at baseline and at >150 weeks of metreleptin treatment was performed. Five female lipodystrophy patients with indication for metreleptin were included. Behavioral aspects of hunger- and satiety regulation were assessed by validated eating behavior questionnaires and visual analog scales assessing hunger and satiety feelings before and after a standardized meal. RESULTS Hunger rated on visual analog scales at 120 min after the meal significantly decreased from 46 ± 10 mm at baseline to 17 ± 6 mm at long-term assessment. Furthermore, satiety at 5 and 120 min after the meal significantly increased from baseline to long-term assessment (5 min: 70 ± 7 mm to 87 ± 3 mm; 120 min: 43 ± 10 mm to 79 ± 8 mm). On the Three Factor Eating Questionnaire, the mean value of factor 3 (hunger) significantly decreased from 9.2 ± 0.2 at baseline to 2.6 ± 1.5 at long-term assessment. In the Inventory of Eating Behavior and Weight Problems Questionnaire, mean values for scale 2 (strength and triggering of desire to eat) and scale 7 (cognitive restraint of eating) significantly decreased from baseline (31.6 ± 4.8 and 11.4 ± 2.2, respectively) to long-term assessment (14.0 ± 2.1 and 10.0 ± 1.9). CONCLUSION First evidence is presented that long-term metreleptin treatment of >150 weeks has sustained effects on eating behavior with increased satiety, as well as reduced hunger and hunger-related measures.
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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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Hunger is the best spice: an fMRI study of the effects of attention, hunger and calorie content on food reward processing in the amygdala and orbitofrontal cortex.
Siep, N, Roefs, A, Roebroeck, A, Havermans, R, Bonte, ML, Jansen, A
Behavioural brain research. 2009;(1):149-58
Abstract
Research indicates that dysfunctional food reward processing may contribute to pathological eating behaviour. It is widely recognized that both the amygdala and the orbitofrontal cortex (OFC) are essential parts of the brain's reward circuitry. The aims of this fMRI study were (1) to examine the effects of food deprivation and calorie content on reward processing in the amygdala and the OFC, and (2) to examine whether an explicit evaluation of foods is necessary for OFC, but not amygdalar activity. Addressing the first aim, healthy females were presented with high and low calorie food pictures while being either hungry or satiated. For the second aim, attention focus was manipulated by directing participants' attention either to the food or to a neutral aspect. This study shows that hunger interacts with the energy content of foods, modulating activity in the posterior cingulate cortex, medial OFC, insula, caudate putamen and fusiform gyrus. Results show that satiated healthy females show an increased reward processing in response to low calorie foods. Confirming our hypothesis, food deprivation increased activity following the presentation of high calorie foods, which may explain why treatments of obesity energy restricting diets often are unsuccessful. Interestingly, activity in both the amygdala and mOFC was only evident when participants explicitly evaluated foods. However, attention independent activity was found in the mPFC following the high calorie foods cues when participants where hungry. Current findings indicate that research on how attention modulates food reward processing might prove especially insightful in the study of the neural substrates of healthy and pathological eating behaviour.
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Cerebral processing of food-related stimuli: effects of fasting and gender.
Uher, R, Treasure, J, Heining, M, Brammer, MJ, Campbell, IC
Behavioural brain research. 2006;(1):111-9
Abstract
To maintain nutritional homeostasis, external food-related stimuli have to be evaluated in relation to the internal states of hunger or satiety. To examine the neural circuitry responsible for integration of internal and external determinants of human eating behaviour, brain responses to visual and complex gustatory food-related stimuli were measured using functional magnetic resonance imaging in 18 healthy non-smokers (10 women, 8 men). Each individual was studied on two occasions, the order of which was counterbalanced; after eating as usual and after 24 h fasting. Raised plasma free fatty acids and lower insulin and leptin concentrations confirmed that participants fasted as requested. When fasted, participants reported more hunger, nervousness and worse mood and rated the visual (but not gustatory) food-related stimuli as more pleasant. The effect of fasting on hunger was stronger in women than in men. No circuitry was identified as differentially responsive in fasting compared to satiety to both visual and gustatory food-related stimuli. The left insula response to the gustatory stimuli was stronger during fasting. The inferior occipito-temporal response to visual food-related stimuli also tended to be stronger during fasting. The responses in the occipito-temporal cortex to visual and in the insula to gustatory stimuli were stronger in women than in men. There was no interaction between gender and fasting. In conclusion, food reactivity in modality-specific sensory cortical areas is modulated by internal motivational states. The stronger reactivity to external food-related stimuli in women may be explored as a marker of gender-related susceptibility to eating disorders.
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Energy density and weight of food effect short-term caloric compensation in men.
Mazlan, N, Horgan, G, Stubbs, RJ
Physiology & behavior. 2006;(4):679-86
Abstract
OBJECTIVE The purpose of the study was to examine the effect of energy density and food weight (volume) on subsequent intake. DESIGN Sixteen lean men were each studied four times during a 2-d protocol at the Rowett's Human Nutrition Unit. On day 1, subjects were fed a mandatory diet at 1.6 x resting metabolic rate (RMR). On day 2, during the mandatory morning period (08.30-12.30) subjects consumed a fixed breakfast (08.30) plus a snack (10.30) in one of four treatments [with values in weight (kg), ED (kJ/100g), Energy (MJ)]: (i) zero intake, 0:0:0 (ii) low energy density (LED), 0.615: 400: 2.46; (iii) high energy density (HED), 0.615: 800: 4.92; (iv) 2 x LED, 1.225: 400: 4.91. From 12.30, throughout the remainder of the day, subjects had ad libitum access to 15 high-protein, 15 high-fat and 15 high-carbohydrate foods. Motivation to eat was tracked hourly using 100 mm line scales. RESULTS ANOVA showed subjects were hungrier after the zero and LED treatments in the mandatory period (p<0.001). Lunch time EI was 5.0, 3.1, 4.2 and 3.2 MJ on the zero, HED, LED and 2 x LED treatments, respectively (p<0.001). Total ad libitum EI was 11.7, 9.6, 10.3 and 9.5 MJ/d, respectively (p=0.033). Total ad libitum plus mandatory intakes amounted to 11.7, 14.5, 12.6 and 14.4 MJ/d, respectively (p=0.001). Corresponding food intakes were 2.18, 2.39, 2.51 and 3.06 kg/d, respectively (p<0.001). CONCLUSIONS The present study showed that subjects respond to both the amount of food eaten in the morning and to the energy density of those foods. However, compensation was only partial and short-term. Subjects only compensated EI by approximately 40% and that compensation only occurred at the next meal.