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Anabolika Online BestellenShort-chain fatty acids SCFAsmetabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, propionate results of an effect of colonic propionate on the human brain propionate results reward-based eating best steroids to build muscle fast propionate results currently unavailable. We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation.
Short-chain fatty acids SCFAs , metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable.
We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging fMRI food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production.
Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal.
Our results suggest that colonic propionate production may play an important role in attenuating reward-based eating behavior via striatal pathways, independent of changes in plasma PYY and GLP This trial was registered at clinicaltrials.
See corresponding editorial on page 1. Peripheral signals communicate information about current energy balance to the brain to maintain energy homeostasis 1. The hedonic properties and constant availability of highly palatable energy-dense foods promote their overconsumption and weight gain, whereas hedonic and reward-based eating behaviors are in turn influenced by peripheral homeostatic signals such as gut hormones 2 — 4.
Hedonic responses to food are thought to involve a network of corticolimbic brain structures, and are modulated by emotional and cognitive factors, as well as sensory cues and anticipated reward.
There is increasing evidence that metabolites produced by the colonic microbiota may affect central appetite regulation 5 — 7. Resistant starch RS 12 supplementation alters activation in hypothalamic nuclei and gene expression of neuropeptides involved in appetite regulation in rodents 5 , 6.
The consumption of nondigestible carbohydrates NDCs also reduces energy intake and weight gain in animal models 8 — Several physiologic benefits associated with the consumption of RS and other NDCs may be mediated through the actions of their fermentation products, namely, short-chain fatty acids SCFAs. The principal SCFAs produced via bacterial fermentation are acetate, propionate, and butyrate, present in the colon in the approximate molar ratio of Our research group demonstrated that increasing circulating acetate directly suppresses appetite via central hypothalamic mechanisms in rodents 7.
Our recent findings from human studies suggest that propionate may also be an important SCFA contributing to appetite regulation The acute intake of an inulin-propionate ester IPE , which selectively increases colonic propionate production, reduced ad libitum energy intake and increased plasma concentrations of the anorexigenic gut hormones glucagon-like peptide 1 GLP-1 and peptide YY PYY , supporting results of in vitro experiments 12 , Furthermore, a long-term elevation in colonic propionate production protected against weight gain and reduced hepatic lipid content However, to date, to our knowledge, there are no studies demonstrating an effect of SCFAs on human brain food-reward responses to influence eating behavior.
In the present study, we examined the effect of an acute increase in colonic propionate production on energy intake and brain regions involved with reward processing and hedonic eating, including caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex OFC 15 , 16 , in healthy nonobese men in a randomized crossover design Figure 1.
We used fMRI to measure activation by the BOLD signal in these regions of interest during an established food evaluation task that used high energy HE — and low energy LE —density food pictures primary outcome measure 3 , 17 — We hypothesized that increasing colonic propionate production after intake of IPE would reduce anticipatory reward responses during evaluation of food pictures, a measure of food cue reactivity, compared with control inulin via the stimulation of the anorexigenic gut hormones GLP-1 and PYY 4 , and would reduce ad libitum energy intake.
Overview of timings of blood sampling, VAS ratings, breath hydrogen recordings, and scanning protocol. Adapted from reference 17 with permission. Further details are given in Supplemental Methods. Subjects were recruited via public advertisement and a healthy volunteer database.
Exclusion criteria included the following: IPE designed for targeted delivery of propionate to the colon was produced as previously described Inulin was chosen as a control supplement, with the use of the same inulin used to prepare both the IPE and control supplements. This controlled for residual fermentation of the backbone NDC.
In vitro fermentations of IPE and inulin suggest comparable increases in acetate and butyrate production; thus, any differences in our outcome measures can be attributed to the preferential increase in propionate production with IPE Twenty healthy men participated in this randomized, placebo-controlled, within-subject, single-blind crossover study.
Weight, height, and body fat measurements were collected with the use of bioimpedance analysis BC analyzer; Tanita UK. At each visit, subjects completed a Positive and Negative Affect Schedule to measure mood during the previous week Serial venous blood samples were collected via a peripheral cannula to assay plasma and serum metabolite and hormone concentrations over study visits Figure 1.
Breath hydrogen concentration, a marker of colonic fermentation 22 , was measured with the use of a handheld breath hydrogen analyzer EC60 Gastrolyser Breath Hydrogen Monitor; Bedfont Scientific , and twelve mm visual analog scales were completed to assess serial subjective appetite and mood ratings Figure 1.
At 0 min, a standard breakfast containing 10 g IPE treatment or 10 g inulin control was provided to subjects in a randomized order via sealed envelope. Breakfast was a chocolate milkshake and snack bar Lunch min was a cheese sandwich and snack bar kcal; This time point was chosen based on previous results from an acute study that suggest successful delivery of IPE to the colon and increased plasma gut hormone concentrations after min Finally, a savory meal of tomato and mozzarella pasta bake per g: Subjects were instructed to eat until they felt comfortably full.
Five of the first 12 subjects who completed the study consumed all of the food presented at the meal. As a result, data on food intake for these 5 subjects were removed from analysis of ad libitum food consumption and the amount of food presented to the final 8 subjects was increased.
All subjects underwent an MRI scan from to min as previously described 17 — After an initial practice run with the use of pictures of animals, subjects had a resting-state fMRI scan lasting 10 min followed by the food picture fMRI paradigm at min Figure 1. Subjects had an auditory—motor—visual AMV fMRI task at min, followed by collection of structural magnetic resonance brain scans, including high-resolution T1-weighted scans for image registration Figure 1.
In a block design, subjects performed 2 of each of the following tasks simultaneously: Higher-level analysis used a fixed-effect model to combine the 2 runs to determine activation for the following contrasts: Similar analysis was performed for the single-run AMV paradigm including the onsets of each task auditory, motor, and visual to contrast activation during performance of each task with that when it was not being performed.
Whole-brain analysis was performed separately with the use of FEAT v6. An anatomic region of interest for the hypothalamus was also generated with the use of the mean of all anatomical T1 scans for the subjects in the current study.
A composite score was calculated with the use of the following formula Glucose analysis was performed at the Department of Biochemistry, Hammersmith Hospital, with the use of a ci analyzer enzymatic method Abbott Diagnostics.
PYY and GLP-1 were measured with the use of previously established in-house specific and sensitive radioimmunoassay 24 , Subject characteristics are given in Table 1. Age and anthropometric data are means of first and second study visit measurements. Breath hydrogen concentrations were significantly elevated above baseline concentrations min after subjects received either inulin or IPE and stayed significantly elevated until the end of the study visit Figure 2.
This suggests that the fermentation of IPE and the release of propionate in the colon occurred in a time course similar to that previously reported Breath hydrogen concentrations after IPE or control inulin. IPE, inulin-propionate ester; ppm, parts per million. Data on energy intake for 5 subjects were removed from analysis of ad libitum energy intake because these subjects consumed all presented food during one or both visits see Methods.
IPE treatment significantly reduced energy intake by 9. Energy intake at ad libitum meal after IPE or control inulin. The horizontal solid line in panel B represents the mean 9. An AMV control task was performed to look for nonspecific changes in the BOLD signal between treatments, as previously described 17 — Food picture appeal ratings and rating reaction times after consumption of IPE or control inulin.
Compared with baseline, there was no significant increase in serum acetate or propionate concentrations min after subjects received IPE or control inulin Table 2. For serum butyrate, there was a significant increase in concentrations min after subjects received both IPE and control inulin compared with baseline.
For 0 min compared with min calculated with the use of paired-samples t tests within each treatment. There was no significant effect of IPE treatment on composite appetite visual analog scale ratings Supplemental Figure 5. There were no significant differences between treatment visits in potential confounding variables that may have affected the BOLD signal or hedonic response to food pictures, including in BMI, percentage body fat, mood, total energy intake on the previous day, ratings of nausea, sleepiness, stress or anxiety, or head motion during the fMRI task Supplemental Table 3.
As expected, the change in energy intake between treatments was positively correlated with the change in composite appetite visual analog scale ratings between treatments Supplemental Table 4. However, there was no significant correlation between elevated colonic propionate on the BOLD signal to HE food in the caudate or nucleus accumbens, or in the mean of both regions, and the effect of increased colonic propionate on HE food appeal, or in composite appetite visual analog scale ratings Supplemental Table 4.
We used an established fMRI food evaluation paradigm to assess the effects of elevated colonic propionate on brain responses during food picture evaluation in a priori regions of interest previously associated with reward processing and hedonic eating behavior. An acute increase in colonic propionate reduced the BOLD signal during an evaluation of food pictures in the caudate dorsal striatum and nucleus accumbens ventral striatum in nonobese men, which was greater for HE than for LE foods.
Increased colonic propionate production also reduced the appeal of HE food pictures and prolonged the time taken to rate their appeal, an implicit measure that suggested reduced wanting 17 , Furthermore, this reduced activation in striatal brain reward systems was accompanied by a reduction in ad libitum energy intake.
This is the first time, to our knowledge, that an acute increase in colonic propionate or any other SCFA has been shown to significantly reduce anticipatory food hedonic responses and associated BOLD signal changes in brain regions associated with reward processing in humans.
Changes in striatal the BOLD signal to food cues previously have been associated with physiologically relevant alterations in food reward processing and eating behavior 3 , 28 — In the satiated fed compared with fasted state, there is a reduction in the ventral striatum BOLD signal during evaluation of HE compared with LE food pictures, and a preferential reduction in the appeal of HE foods, when an fMRI paradigm identical to that of the current study is used 3.
The reduced ventral striatum BOLD signal to HE food pictures in the fed compared with fasted state has also been correlated with a subsequent reduction in ad libitum energy intake Similarly, satiation decreases BOLD responses to food taste in the nucleus accumbens 31 , whereas duration of food deprivation correlates with a greater caudate BOLD signal in response to actual and anticipated receipt of palatable food Satiation also decreases regional cerebral blood flow at rest, another marker of neuronal activity, in the caudate and nucleus accumbens Greater activation in the nucleus accumbens to food pictures is predictive of future snack consumption and reduced weight loss success in an obesity lifestyle intervention 30 , Alterations in caudate activation to actual or anticipated receipt of HE palatable food have been linked to genetic variations in the dopamine receptor D2 DRD2 gene, which is highly expressed in the striatum and linked to increased BMI, familial risk of obesity, and prospective weight gain 34 — In addition, after Roux-en-Y gastric bypass RYGB surgery, obese patients have lower activation in the caudate and nucleus accumbens when HE foods are evaluated, and have lower HE food appeal than patients after gastric banding surgery RYGB has been associated with increased colonic propionate production in animal models This evidence supports a role of the striatum in altered reward processing and food consumption patterns.
It suggests that increased colonic propionate may modulate the engagement of this brain-reward circuit, resulting in a reduction in energy intake, although we could not demonstrate a direct correlation between changes in the BOLD signal and energy intake in our study. RS supplementation reduces activity in hypothalamic appetite regulation centers as assessed by manganese-enhanced MRI and stimulates anorexigenic hypothalamic pro-opiomelanocortin expression in rodents 5 , 6.
Acetate itself suppresses appetite via central hypothalamic mechanisms 7 and also has been shown to have other central effects
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TRENTIN and TURNER () and CURTISS () had obtained similar results when administering oestradiol propionate. REECE and LEATHEM () had. The effects of testosterone propionate on the mouse kidney were examined The application of androgen in male and female mice results in hypertrophy of the. of testosterone propionate in oil solution, gave the following results: male rats kept for 6 weeks in constant darkness (beginning on the 21st day of life) showed .