Addition of low sodium does not increase sensitivity to glucose in wild-type mice, or lead to partial glucose taste detection in T1R3 knock-out mice.

The sodium glucose cotransporter 1 (SGLT1) has been proposed as a non-T1R glucosensor contributing to glucose taste. Studies have shown that the addition of NaCl at very weak concentrations to a glucose stimulus can enhance signaling in the gustatory nerves of mice and significantly lower glucose detection thresholds in humans. Here, we trained mice with (wild-type; WT) and without (knockout; KO) a functioning T1R3 subunit on a two-response operant detection task to differentially respond to the presence or absence of a taste stimulus immediately after sampling. After extensive training (∼40 sessions), KO mice were unable to reliably discriminate 2 M glucose+0.01 M NaCl from 0.01 M NaCl alone, but all WT mice could. We then tested WT mice on a descending array of glucose concentrations (2.0-0.03 M) with the addition of 0.01 M NaCl vs. 0.01 M NaCl alone. The concentration series was then repeated with glucose alone vs. water. We found no psychophysical evidence of a non-T1R taste transduction pathway involved in the detection of glucose. The addition of NaCl to glucose did not lower taste detection thresholds in WT mice, nor did it render the stimulus detectable to KO mice, even at 2 M. The proposed pathway must contribute to functions other than sensory-discriminative detection, at least when tested under these conditions. Detection thresholds were also derived for fructose and found to be 1/3 log10 lower than for glucose, but highly correlated (r = 0.88) between the two sugars, suggesting that sensitivity to these stimuli in this task was based on a similar neural process.

Lingual Taste Nerve Transection Alters Food Selection, Relative Macronutrient Intake, and Meal Patterns in Rats Consuming a Cafeteria Diet without Changing Total Energy Intake.

The control of ingestive behavior is complex and involves input from many different sources, including the gustatory system. Signals transmitted via the taste nerves trigger responses that promote or discourage ingestion. The lingual taste nerves innervate 70% of taste buds, yet their role in the control of food selection and intake remarkably remains relatively underinvestigated. Here we used our custom five-item Food Choice Monitor to compare postsurgical behavioral responses to chow and a five-choice cafeteria diet (CAF) between male rats that had sham surgery (SHAM) or histologically verified transection of the chorda tympani and glossopharyngeal nerves (2NX). Compared with SHAM rats, 2NX rats ate significantly more of the high-fat CAF foods. The altered food choices led to dramatically increased fat intake and substantially reduced carbohydrate intake by 2NX vs SHAM rats. Furthermore, whether offered chow or CAF, 2NX rats ate fewer, larger meals each day. Eating rates implied that, compared with SHAM, 2NX rats were equally motivated to consume CAF but less motivated to eat chow. Even with these differences, energy intake and weight gain trajectories remained similar between SHAM and 2NX rats. Although some rats experienced CAF before surgery, contrary to our expectations, the effects of prior CAF experience on postsurgical eating were minimal. In conclusion, although total energy intake was unaffected, our results clearly indicate that information from one or both lingual taste nerves has a critical role in food selection, regulation of macronutrient intake, and meal termination but not long-term energy balance.

The Nature of Available Choices Affects the Intake and Meal Patterns of Rats Offered a Palatable Cafeteria-Style Diet.

Humans choose which foods they will eat from multiple options. The use of cafeteria-style diets with rodent models has increased our understanding of how a multichoice food environment affects eating and health. However, the wide variances in energy density, texture, and the content of micronutrients, fiber, and protein can be interpretatively problematic when human foodstuffs are used to create rodent cafeteria diets. We minimized these differences with a custom rodent cafeteria diet (ROD) that varied similarly to a previously used human-foods cafeteria diet (HUM) in fat and sugar content. Here, we used our custom Five-Item Food Choice Monitor to compare the intake and meal patterns of rats offered ROD and HUM in a crossover design. Compared with chow, rats consumed more calories, sugar, and fat and less protein and carbohydrate while on either of the choice diets (p < 0.05). While energy intake was similar between HUM and ROD, there were differences in the responses. Rats consumed more of the low-fat, low-sugar choice on the ROD compared with the nutritionally similar choice on the HUM leading to differences in fat and carbohydrate intake between the diets (p < 0.05). The stability of macronutrient intake while on either choice diet suggests macronutrient intake is determined by the available foods and is strongly regulated. Therefore, interpretative consideration must be given to the nature of food choices in the context of available options when interpreting cafeteria-diet intake.

Assessing daily energy intake in adult women: validity of a food-recognition mobile application compared to doubly labelled water.

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight (n = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland-Altman plots, paired difference tests, and Pearson's correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = -329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = -543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard (p < 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ (R2 = 27%, p = 0.50) or 24HR (R2 = 34%, p = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings. Clinical trial registration: This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596).

Chronic Semaglutide Treatment in Rats Leads to Daily Excessive Concentration-Dependent Sucrose Intake.

Context: The glucagon-like peptide-1 receptor (GLP-1R) agonist semaglutide (SEMA) produces 15% weight loss when chronically administered to humans with obesity. Methods: In 2 separate experiments, rats received daily injections of either vehicle (VEH) or SEMA starting at 7 µg/kg body weight (BW) and increasing over 10 days to the maintenance dose (70 µg/kg-BW), emulating clinical dose escalation strategies. Results: During dose escalation and maintenance, SEMA rats reduced chow intake and bodyweight. Experiment 2 meal pattern analysis revealed that meal size, not number, mediated these SEMA-induced changes in chow intake. This suggests SEMA affects neural processes controlling meal termination and not meal initiation. Two-bottle preference tests (vs water) began after 10 to 16 days of maintenance dosing. Rats received either an ascending sucrose concentration series (0.03-1.0 M) and 1 fat solution (Experiment 1) or a 4% and 24% sucrose solution in a crossover design (Experiment 2). At lower sucrose concentrations, SEMA-treated rats in both experiments drank sometimes >2× the volume consumed by VEH controls; at higher sucrose concentrations (and 10% fat), intake was similar between treatment groups. Energy intake of SEMA rats became similar to VEH rats. This was unexpected because GLP-1R agonism is thought to decrease the reward and/or increase the satiating potency of palatable foods. Despite sucrose-driven increases in both groups, a significant bodyweight difference between SEMA- and VEH-treated rats remained. Conclusion: The basis of the SEMA-induced overconsumption of sucrose at lower concentrations relative to VEH controls remains unclear, but the effects of chronic SEMA treatment on energy intake and BW appear to depend on the caloric sources available.

A Novel Mechanism for T1R-Independent Taste Responses to Concentrated Sugars.

Recent findings from our laboratory demonstrated that the rostral nucleus of the solitary tract (rNST) retains some responsiveness to sugars in double-knock-out mice lacking either the T1R1+T1R3 (KO1+3) or T1R2+T1R3 (KO2+3) taste receptor heterodimers. Here, we extended these findings in the parabrachial nucleus (PBN) of male and female KO1+3 mice using warm stimuli to optimize sugar responses and employing additional concentrations and pharmacological agents to probe mechanisms. PBN T1R-independent sugar responses, including those to concentrated glucose, were more evident than in rNST. Similar to the NST, there were no "sugar-best" neurons in KO1+3 mice. Nevertheless, 1000 mm glucose activated nearly 55% of PBN neurons, with responses usually occurring in neurons that also displayed acid and amiloride-insensitive NaCl responses. In wild-type (WT) mice, concentrated sugars activated the same electrolyte-sensitive neurons but also "sugar-best" cells. Regardless of genotype, phlorizin, an inhibitor of the sodium-glucose co-transporter (SGLT), a component of a hypothesized alternate glucose-sensing mechanism, did not diminish responses to 1000 mm glucose. The efficacy of concentrated sugars for driving neurons broadly responsive to electrolytes implied an origin from Type III taste bud cells. To test this, we used the carbonic anhydrase (CA) inhibitor dorzolamide (DRZ), previously shown to inhibit amiloride-insensitive sodium responses arising from Type III taste bud cells. Dorzolamide had no effect on sugar-elicited responses in WT sugar-best PBN neurons but strongly suppressed them in WT and KO1+3 electrolyte-generalist neurons. These findings suggest a novel T1R-independent mechanism for hyperosmotic sugars, involving a CA-dependent mechanism in Type III taste bud cells.SIGNIFICANCE STATEMENT Since the discovery of Tas1r receptors for sugars and artificial sweeteners, evidence has accrued that mice lacking these receptors maintain some behavioral, physiological, and neural responsiveness to sugars. But the substrate(s) has remained elusive. Here, we recorded from parabrachial nucleus (PBN) taste neurons and identified T1R-independent responses to hyperosmotic sugars dependent on carbonic anhydrase (CA) and occurring primarily in neurons broadly responsive to NaCl and acid, implying an origin from Type III taste bud cells. The effectiveness of different sugars in driving these T1R-independent responses did not correlate with their efficacy in driving licking, suggesting they evoke a nonsweet sensation. Nevertheless, these salient responses are likely to comprise an adequate cue for learned preferences that occur in the absence of T1R receptors.

The elusive cephalic phase insulin response: triggers, mechanisms, and functions.

The cephalic phase insulin response (CPIR) is classically defined as a head receptor-induced early release of insulin during eating that precedes a postabsorptive rise in blood glucose. Here we discuss, first, the various stimuli that elicit the CPIR and the sensory signaling pathways (sensory limb) involved; second, the efferent pathways that control the various endocrine events associated with eating (motor limb); and third, what is known about the central integrative processes linking the sensory and motor limbs. Fourth, in doing so, we identify open questions and problems with respect to the CPIR in general. Specifically, we consider test conditions that allow, or may not allow, the stimulus to reach the potentially relevant taste receptors and to trigger a CPIR. The possible significance of sweetness and palatability as crucial stimulus features and whether conditioning plays a role in the CPIR are also discussed. Moreover, we ponder the utility of the strict classical CPIR definition based on what is known about the effects of vagal motor neuron activation and thereby acetylcholine on the ß-cells, together with the difficulties of the accurate assessment of insulin release. Finally, we weigh the evidence of the physiological and clinical relevance of the cephalic contribution to the release of insulin that occurs during and after a meal. These points are critical for the interpretation of the existing data, and they support a sharper focus on the role of head receptors in the overall insulin response to eating rather than relying solely on the classical CPIR definition.

Early Postoperative Exposure to High-Fat Diet Does Not Increase Long-Term Weight Loss or Fat Avoidance After Roux-en-Y Gastric Bypass in Rats.

Background: Bariatric surgery alters food preferences in rats and reportedly decreases desire to consume high-fat high-sugar food in humans. The aim of this study was to investigate whether early post-operative exposure to high-fat food could increase body weight loss after Roux-en-Y gastric bypass (RYGB) by triggering fat avoidance. Methods: Male Wistar rats underwent either RYGB (n = 15) or sham-operations (n = 16). Preoperatively a standardized 4-choice cafeteria diet [dietary options: low-fat/low-sugar (LFLS), low-fat/high-sugar (LFHS), high-fat/low-sugar (HFLS), high-fat/high-sugar (HFHS)] was offered. First, each option was available for 4 days, thereafter rats were offered the 4 options simultaneously for 3 days preoperatively. Post-surgery, 8 rats in the RYGB- and 8 in the sham-group were exposed to a high-fat content diet (Oatmeal + 30% lard, OM+L) for 10 days, while 7 RYGB rats and 8 sham-rats received OM alone. From the 11th postoperative day, the 4-choice cafeteria diet was reintroduced for 55-days. The intake of all available food items, macronutrients and body weight changes were monitored over 8 weeks. Main outcomes were long-term body-weight and daily change in relative caloric intake during the postoperative cafeteria period compared to the preoperative cafeteria. Results: During the first 12 days of postoperative cafeteria access, RYGB-rats exposed to OM+L had a higher mean caloric intake per day than RYGB rats exposed to OM alone (Δ10 kCal, P adj = 0.004), but this difference between the RYGB groups disappeared thereafter. Consequently, in the last 33 days of the postoperative cafeteria diet, the mean body weight of the RYGB+OM+L group was higher compared to RYGB+OM (Δ51 g, P adj < 0.001). RYGB rats, independently from the nutritional intervention, presented a progressive decrease in daily consumption of calories from fat and increased their daily energy intake mainly from non-sugar carbohydrates. No such differences were detected in sham-operated controls exposed to low- or high fat postoperative interventions. Conclusion: A progressive decrease in daily fat intake over time was observed after RYGB, independently from the nutritional intervention. This finding confirms that macronutrient preferences undergo progressive changes over time after RYGB and supports the role of ingestive adaptation and learning. Early postoperative exposure to high-fat food failed to accentuate fat avoidance and did not lead to superior weight loss in the long-term.

Burst-pause criterion derivation for drinkometer measurements of ingestive behavior.

The drinkometer is a promising device for the study of ingestive behavior of liquid meals in humans. It can be used to investigate behavior in different target populations. However, ingestive behavior has a great variability across study participants. Therefore, a new analytical approach is required for the extraction and analysis of drinkometer-derived data that could account for this variability. We developed an optimized protocol to predict an optimal burst-pause criterion (PC) for the extraction of PC-dependent microstructural parameters of ingestive behavior. These describe the microstructure of bursts, while PC-independent parameters describe the microstructure of sucks. Therefore, a PC is required to analyze separately two physiologically different parts of behavior. To accomplish this burst-pause criterion derivation (BPCD), a Gaussian Mixture Model (GMM) was built for estimation of two probability density functions (PDFs). These model the distribution of inter-suck intervals (ISIs) and inter-burst intervals (IBIs), respectively. The PC is defined at the intersection point of the two density functions. A Kaplan-Meier (KM) survival analysis was performed for post-hoc verification of the fit of the predicted optimal PC to the ISI distribution. In this protocol paper, we present a walkthrough of the data analysis of drinkometer-derived data for the measurement of microstructure of ingestive behavior based on previous results published by our group [1].•Standardization of the burst-pause criterion derivation for drinkometer measurements of ingestive behavior.•All codes are publicly available in a repository.•The method can be easily adapted to studies with larger sample size or more than one study stimulus.

A Subregion of Insular Cortex Is Required for Rapid Taste-Visceral Integration and Consequent Conditioned Taste Aversion and Avoidance Expression in Rats.

Postingestive signals are important for shaping appetitive and consummatory responses, but the brain mechanisms required to assimilate interoceptive events with those at the frontlines of ingestion (taste-guided) are poorly understood. Here, we investigated whether an insular cortex (IC) region, which receives viscerosensory input, including gustatory, is required to modify taste-elicited consummatory reactions in response to a real-time interoceptive change using a serial taste reactivity (TR) test where the rats' oromotor and somatic reactions to intraoral (IO) infusions of sucrose were periodically assessed over 45 min following lithium chloride (LiCl) administration. Results showed that neurally-intact rats shifted from an ingestive repertoire to an aversive one as LiCl took effect. Overall, this hedonic shift was delayed in rats with bilateral neurotoxic IC lesions. Rats with greater neuronal loss in posterior gustatory IC displayed fewer aversive reactions to sucrose following this initial LiCl injection. We further assessed whether the failure to integrate interoceptive feedback with ongoing taste-guided behavior impaired acquisition and/or expression of conditioned aversion and/or avoidance in these same rats. Although, as a group, LiCl-injected rats with IC lesions subsequently avoided the sugar in a 48-h two-bottle test, their preference for sucrose was significantly greater than that of the LiCl-injected neurally-intact rats. Overall lesion size, as well as proportion of the posterior gustatory and/or anterior visceral IC were each associated with impaired avoidance. These findings reveal new roles for the posterior gustatory and anterior visceral ICs in multisensory integrative function.

A new apparatus to analyze meal-related ingestive behaviors in rats fed a complex multi-food diet.

The measurement of the size and timing of meals provides critical insight into the processes underlying food intake. While most work has been conducted with a single food or fluid, the availability of food choices can also influence eating and interact with these processes. The 5-Item Food Choice Monitor (FCM), a device that continuously measures eating and drinking behaviors of rats provided up to 5 foods and 2 fluids simultaneously, was designed to allow study of food choices simultaneously with meal patterns. To validate this device, adult male and female (n = 8 each) Sprague-Dawley rats were housed in the FCM. Food and fluid intake were measured continuously (22-h/day) while rats were presented water and powdered chow. Then a cafeteria diet of 5 foods varying in macronutrient content, texture, and flavors were offered along with water. Lastly, the 5 foods were offered along with 0.3 M sucrose and water. Analyses were conducted to find optimal criteria for parceling ingestive behavior into meals, and then meal patterns were quantified. Total intake, as assessed by FCM software, was in good concordance with that measured by an independent scale. A minimum meal size of 1 kcal and a meal termination criterion of 15-min accounted for >90% of total intake and produced meal dynamics that were in register with the literature. Use of the cafeteria diet allowed comparisons between meal patterns with a single food versus a multi-food diet, as well as analyses of macronutrient-related food choices across subsets of meals. The FCM proved to accurately measure food intake over a 22-h period and was able to detect differences and similarities in the meal patterns of rats as a function of sex and food choice availability. Combined with any number of experimental manipulations, the FCM holds great promise in the investigation of the physiological and neural controls of ingestive behavior in a dietary environment that allows food choices, more closely emulating human eating conditions.

The Effects of Roux-en-Y Gastric Bypass on Glucose- vs. Fructose-Associated Conditioned Flavor Preference.

In rodents, repeated single-bottle exposures to distinctly flavored isocaloric glucose and fructose solutions, two sugars with different metabolic pathways, eventually lead to a preference for the former. Because Roux-en-Y gastric bypass (RYGB) surgery decreases preference for and intake of sugar solutions in rats, we tested whether RYGB would curtail the conditioning of a preference for a glucose-paired vs. fructose-paired flavor. RYGB (♂ n=11; ♀ n=10) and sham-operated (SHAM; ♂ n=9; ♀ n=10) rats were trained with a single bottle (30 min/day) containing 8% glucose solution flavored with either 0.05% grape or cherry Kool-Aid (Glu/CSG) or 8% fructose solution with the alternative Kool-Aid flavor (Fru/CSF) in an alternating fashion for 8 days. To determine baseline preferences, a 4-day 30-min two-bottle test was used to assess preference for Glu/CSG vs. Fru/CSF before training. After training, 2-day 30-min two-bottle tests assessed preference for the a) Glu/CSG (CSG-flavored 8% glucose solution) vs Fru/CSF (CSF-flavored 8% fructose solution), b) CSG- vs. CSF-flavored mixture of 4% glucose & 4% fructose (isocaloric), c) CSG- vs. CSF-flavored 0.2% saccharin ("sweet", no calories), and d) CSG- vs. CSF-flavored water. During training, only male SHAM rats demonstrated progressively increased intake of Glu/CSG over Fru/CSF, and female SHAM rats displayed a trend. RYGB eliminated any difference in single-bottle intake of these solutions during training, regardless of sex. Like their male and female SHAM counterparts, male RYGB rats displayed a conditioned preference for the CSG-associated stimulus in Tests 1-3. Although female RYGB rats displayed acquisition of the conditioned flavor preference in Test 1, unlike the other groups, when the differential sugar cue between the two solutions was removed in Tests 2 and 3, female rats did not display a CSG preference. When the sugar and sweetener cues were both removed on Test 4, all groups displayed some generalization decrement. Thus, RYGB does not compromise the ability of rats to learn and express a glucose- vs. fructose-associated conditioned flavor preference when the exact CS used in training is presented in testing. The mechanistic basis for the sex difference in the effect of RYGB on the generalization decrement observed in this type of flavor preference learning warrants further study.

Association between microstructure of ingestive behavior and body weight loss in patients one year after Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) is one of the most effective procedures in the treatment of obesity. However, the predictive value of the microstructure of ingestion has not been widely investigated in this context. Here, we applied a recently developed drinkometer device to analyze the microstructure of ingestive behavior during a liquid meal in women and investigate whether it correlated with measures of weight loss after RYGB. Macro- and microstructural parameters of ingestive behavior of female patients (n = 24) one year after RYGB were measured in two different test sessions within a period of two weeks using the drinkometer. A Pearson correlation analysis was performed to compare the macro- and microstructural parameters of ingestive behavior with the percentage of total weight loss (%TWL), percentage excess BMI loss (%EBMIL), and body mass index (BMI) one year after RYGB, as well as age. A Bonferroni adjusted p < 0.003 was considered significant for the correlation analysis. For all other statistical tests, a p < 0.05 was considered significant. One year after surgery, a significant body weight loss was achieved in our study population (111.2 ± 15.6 kg vs 73.4 ± 11.7 kg; ***p < 0.001), with a mean%TWL of 33.8% (range: 20.4-48.6%). At the first test session,%TWL correlated with suck duration (r = 0.41, 0.05 > p > 0.003);%EBMIL correlated with both suck duration (r = 0.64, *p < 0.003) and inter-suck intervals (ISIs, r = -0.47, *p < 0.003), and, finally, BMI correlated with suck duration (r = 0.62, *p < 0.003) and ISIs (r = 0.48, *p < 0.003). However, at the second test session, no correlation was found between the body weight loss and the recorded ingestive parameters. Furthermore, no statistically significant difference was found in microstructural parameters of ingestive behavior between the two test sessions even though meal size decreased by 20% on the second visit (342.6.6 ± 167 kcal vs. 271.8 ± 142.8 kcal). A greater body weight loss of patients one year after surgery seems to be associated with longer suck duration and shorter ISIs, but only when the stimulus is tested for the first time by the study participants. This study contributes to the current knowledge about the ingestive behavior of bariatric patients one year after RYGB in terms of its association with the achieved weight loss. The use of the drinkometer device for the measurement of microstructure of ingestive behavior should be further expanded to different research questions and patient subgroups other than good responders. Its possible applications in clinical and behavioral research need to be included in the agenda of bariatric research.

The Influence of Roux-en-Y Gastric Bypass and Diet on NaCl and Sucrose Taste Detection Thresholds and Number of Circumvallate and Fungiform Taste Buds in Female Rats.

Roux-en-Y gastric bypass (RYGB) in rats attenuates preference for, and intake of, sugar solutions. Additionally, maintenance on a high-fat diet (HFD) reportedly alters behavioral responsiveness to sucrose in rodents in short-term drinking tests. Due to the fact that the behavioral tests to date rely on the hedonic value of the stimulus to drive responsiveness, we sought to determine whether taste detection thresholds to sucrose and NaCl are affected by these manipulations as measured in an operant two-response signal detection paradigm. Female rats were maintained on HFD or chow for 10 weeks, at which point animals received either RYGB or SHAM surgery followed by a gel-based diet and then powdered chow. Upon recovery, half of the rats that were previously on HFD were switched permanently to chow, and the other rats were maintained on their presurgical diets (n = 5-9/diet condition × surgery group for behavioral testing). The rats were then trained and tested in a gustometer. There was a significant interaction between diet condition and surgery on NaCl threshold that was attributable to a lower value in RYGB vs. SHAM rats in the HFD condition, but this failed to survive a Bonferroni correction. Importantly, there were no effects of diet condition or surgery on sucrose thresholds. Additionally, although recent evidence suggests that maintenance on HFD alters taste bud number in the circumvallate papillae (CV) of mice, in a subset of rats, we did not find that diet significantly influenced taste pores in the anterior tongue or CV of female rats. These results suggest that any changes in sucrose responsiveness in intake/preference or hedonically oriented tests in rats as a function of HFD maintenance or RYGB are not attributable to alterations in taste sensitivity.

Oromotor and somatic taste reactivity during sucrose meals reveals internal state and stimulus palatability after gastric bypass in rats.

After Roux-en-Y gastric bypass (RYGB), rats consume less high-energy foods and fluids, though whether this reflects a concomitant change in palatability remains unclear. By measuring behavior during intraorally delivered liquid meals across days (1 water, 8 sucrose sessions), we showed that RYGB rats (RYGB, n = 8/sex) consumed less 1.0 M sucrose than their sham surgery counterparts (SHAM, n = 8 males, n = 11 females) but displayed similarly high levels of ingestive taste reactivity responses at the start of infusions. Relative to water, both groups increased intake of sucrose, and ingestive responses were dominated by tongue protrusions rather than mouth movements. Thus, RYGB animals still found sucrose palatable despite consuming less than the SHAM group. As the intraoral infusion progressed but before meal termination, aversive behavior remained low and both RYGB and SHAM animals showed fewer ingestive responses, predominantly mouth movements as opposed to tongue protrusions. This shift in responsiveness unrelated to surgical manipulation suggests negative alliesthesia, or a decreased palatability, as rats approach satiation. Notably, only in RYGB rats, across sessions, there was a striking emergence of aversive behavior immediately after the sucrose meal. Thus, although lower intake in RYGB rats seems independent of the hedonic taste properties of sucrose, taste reactivity behavior in these animals immediately after termination of a liquid meal appears to be influenced by postoral events and reflects a state of nimiety or excessive consumption. Measurement of taste reactivity behaviors during an intraorally delivered meal represents a promising way to make inferences about internal state in nonverbal preclinical models.

Food Intake Following Gastric Bypass Surgery: Patients Eat Less but Do Not Eat Differently.

BACKGROUND: Lack of robust research methodology for assessing ingestive behavior has impeded clarification of the mediators of food intake following gastric bypass (GBP) surgery. OBJECTIVES: To evaluate changes in directly measured 24-h energy intake (EI), energy density (ED) (primary outcomes), eating patterns, and food preferences (secondary outcomes) in patients and time-matched weight-stable comparator participants. METHODS: Patients [n = 31, 77% female, BMI (in kg/m2) 45.5 ± 1.3] and comparators (n = 32, 47% female, BMI 27.2 ± 0.8) were assessed for 36 h under fully residential conditions at baseline (1 mo presurgery) and at 3 and 12 mo postsurgery. Participants had ad libitum access to a personalized menu (n = 54 foods) based on a 6-macronutrient mix paradigm. Food preferences were assessed by the Leeds Food Preference Questionnaire. Body composition was measured by whole-body DXA. RESULTS: In the comparator group, there was an increase in relative fat intake at 3 mo postsurgery; otherwise, no changes were observed in food intake or body composition. At 12 mo postsurgery, patients lost 27.7 ± 1.6% of initial body weight (P < 0.001). The decline in EI at 3 mo postsurgery (-44% from baseline, P < 0.001) was followed by a partial rebound at 12 mo (-18% from baseline), but at both times, dietary ED and relative macronutrient intake remained constant. The decline in EI was due to eating the same foods as consumed presurgery and by decreasing the size (g, MJ), but not the number, of eating occasions. In patients, reduction in explicit liking at 3 mo (-11.56 ± 4.67, P = 0.007) and implicit wanting at 3 (-15.75 ± 7.76, P = 0.01) and 12 mo (-15.18 ± 6.52, P = 0.022) for sweet foods were not matched by reduced intake of these foods. Patients with the greatest reduction in ED postsurgery reduced both EI and preference for sweet foods. CONCLUSIONS: After GBP, patients continue to eat the same foods but in smaller amounts. These findings challenge prevailing views about the dynamics of food intake following GBP surgery. This trial was registered as clinicaltrials.gov as NCT03113305.

Meal Patterns and Food Choices of Female Rats Fed a Cafeteria-Style Diet Are Altered by Gastric Bypass Surgery.

After Roux-en-Y gastric bypass surgery (RYGB), rats tend to reduce consumption of high-sugar and/or high-fat foods over time. Here, we sought to investigate the behavioral mechanisms underlying these intake outcomes. Adult female rats were provided a cafeteria diet comprised of five palatable foodstuffs varying in sugar and fat content and intake was monitored continuously. Rats were then assigned to either RYGB, or one of two control (CTL) groups: sham surgery or a nonsurgical control group receiving the same prophylactic iron treatments as RYGB rats. Post-sur-gically, all rats consumed a large first meal of the cafeteria diet. After the first meal, RYGB rats reduced intake primarily by decreasing the meal sizes relative to CTL rats, ate meals more slowly, and displayed altered nycthemeral timing of intake yielding more daytime meals and fewer nighttime meals. Collectively, these meal patterns indicate that despite being motivated to consume a cafeteria diet after RYGB, rats rapidly learn to modify eating behaviors to consume foods more slowly across the entire day. RYGB rats also altered food preferences, but more slowly than the changes in meal patterns, and ate proportionally more energy from complex carbohydrates and protein and proportionally less fat. Overall, the pattern of results suggests that after RYGB rats quickly learn to adjust their size, eating rate, and distribution of meals without altering meal number and to shift their macronutrient intake away from fat; these changes appear to be more related to postingestive events than to a fundamental decline in the palatability of food choices.

A Comparison of Total Food Intake at a Personalised Buffet in People with Obesity, before and 24 Months after Roux-en-Y-Gastric Bypass Surgery.

Long-term reductions in the quantity of food consumed, and a shift in intake away from energy dense foods have both been implicated in the potent bariatric effects of Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised that relative to pre-operative assessment, a stereotypical shift to lower intake would be observed at a personalised ad libitum buffet meal 24 months after RYGB, driven in part by decreased selection of high energy density items. At pre-operative baseline, participants (n = 14) rated their preference for 72 individual food items, each of these mapping to one of six categories encompassing high and low-fat choices in combination with sugar, complex carbohydrate or and protein. An 18-item buffet meal was created for each participant based on expressed preferences. Overall energy intake was reduced on average by 60% at the 24-month buffet meal. Reductions in intake were seen across all six food categories. Decreases in the overall intake of all individual macronutrient groups were marked and were generally proportional to reductions in total caloric intake. Patterns of preference and intake, both at baseline and at follow-up appear more idiosyncratic than has been previously suggested by verbal reporting. The data emphasise the consistency with which reductions in ad libitum food intake occur as a sequel of RYGB, this being maintained in the setting of a self-selected ad libitum buffet meal. Exploratory analysis of the data also supports prior reports of a possible relative increase in the proportional intake of protein after RYGB.

Evaluation of the impact of gastric bypass surgery on eating behaviour using objective methodologies under residential conditions: Rationale and study protocol.

Gastric bypass surgery leads to significant and sustained weight loss and a reduction in associated health risks in individuals with severe obesity. While reduced energy intake (EI) is the primary driver of weight loss following surgery, the underlying mechanisms accounting for this energy deficit are not well understood. The evidence base has been constrained by a lack of fit-for-purpose methodology in assessing food intake coupled with follow-up studies that are relatively short-term. This paper describes the underlying rationale and protocol for an observational, fully residential study using covert, objective methodology to evaluate changes in 24-hr food intake in patients (n = 31) at 1-month pre-surgery and 3-, 12- and 24-months post-surgery, compared to weight-stable controls (n = 32). The main study endpoints included change in EI, macronutrient intake, food preferences, and eating behaviours (speed, frequency, and duration of eating). Other physiological changes that may influence EI and weight regulation including changes in body composition, circulating appetite hormones, resting metabolic rate, total energy expenditure and gastrointestinal symptoms were also evaluated. Understanding which mechanisms contribute to a reduction in EI and weight loss post-surgery could potentially help to identify those individuals who are most likely to benefit from gastric bypass surgery as well as those that may need more targeted intervention to optimise their weight loss post-surgery. Furthermore, clarification of these mechanisms may also inform targeted approaches for non-surgical treatments of obesity.

Microstructural changes in human ingestive behavior after Roux-en-Y gastric bypass during liquid meals.

BACKGROUNDRoux-en-Y gastric bypass (RYGB) decreases energy intake and is, therefore, an effective treatment of obesity. The behavioral bases of the decreased calorie intake remain to be elucidated. We applied the methodology of microstructural analysis of meal intake to establish the behavioral features of ingestion in an effort to discern the various controls of feeding as a function of RYGB.METHODSThe ingestive microstructure of a standardized liquid meal in a cohort of 11 RYGB patients, in 10 patients with obesity, and in 10 healthy-weight adults was prospectively assessed from baseline to 1 year with a custom-designed drinkometer. Statistics were performed on log-transformed ratios of change from baseline so that each participant served as their own control, and proportional increases and decreases were numerically symmetrical. Data-driven (3 seconds) and additional burst pause criteria (1 and 5 seconds) were used.RESULTSAt baseline, the mean meal size (909.2 versus 557.6 kCal), burst size (28.8 versus 17.6 mL), and meal duration (433 versus 381 seconds) differed between RYGB patients and healthy-weight controls, whereas suck volume (5.2 versus 4.6 mL) and number of bursts (19.7 versus 20.1) were comparable. At 1 year, the ingestive differences between the RYGB and healthy-weight groups disappeared due to significantly decreased burst size (P = 0.008) and meal duration (P = 0.034) after RYGB. The first-minute intake also decreased after RYGB (P = 0.022).CONCLUSIONRYGB induced dynamic changes in ingestive behavior over the first postoperative year. While the eating pattern of controls remained stable, RYGB patients reduced their meal size by decreasing burst size and meal duration, suggesting that increased postingestive sensibility may mediate postbariatric ingestive behavior.TRIAL REGISTRATIONNCT03747445; https://clinicaltrials.gov/ct2/show/NCT03747445.FUNDINGThis work was supported by the University of Zurich, the Swiss National Fund (32003B_182309), and the Olga Mayenfisch Foundation. Bálint File was supported by the Hungarian Brain Research Program Grant (grant no. 2017-1.2.1-NKP-2017-00002).