Preoperative liking and wanting for sweet beverages as predictors of body weight loss after Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND/OBJECTIVES: Patients who receive Roux-en-Y gastric bypass (RYGB) lose more weight than those who receive vertical sleeve gastrectomy (VSG). RYGB and VSG alter hedonic responses to sweet flavor, but whether baseline differences in hedonic responses modulate weight loss after RYGB or VSG remains untested. PARTICIPANTS/METHODS: Male and female candidates (n = 66) for RYGB or VSG were recruited and tested for their subjective liking and wanting ratings of sucrose solutions and flavored beverages sweetened with aspartame. Participants were classified by unsupervised hierarchical clustering for their liking and wanting ratings of sucrose and aspartame. Participant liking ratings were also used in a supervised classification using pre-established categories of liking ratings (liker, disliker, and inverted u-shape). Effects of categories obtained from unsupervised or supervised classification on body weight loss and their interaction with surgery type were analyzed separately at 3 and 12 months after surgery using linear models corrected for sex and age. RESULTS: RYGB participants lost more body weight compared with VSG participants at 3 and 12 months after surgery (P < 0.001 for both time points). Unsupervised clustering analysis identified clusters corresponding to high and low wanting or liking ratings for sucrose or aspartame. RYGB participants in high-wanting clusters based on sucrose, but not aspartame, lost more weight than VSG at both 3 (P = 0.01) and 12 months (P = 0.03), yielding a significant cluster by surgery interaction. Categories based on supervised classification using liking ratings for sucrose or aspartame showed no significant effects on body weight loss between RYGB and VSG participants. CONCLUSIONS: Classification of patients into high/low-wanting ratings for sucrose before surgery can predict differential body weight loss after RYGB or VSG in adults and could be used to advise on surgery type.

Noise-induced sleep disruption increases weight gain and decreases energy metabolism in female rats.

BACKGROUND/OBJECTIVES: Inadequate sleep increases obesity and environmental noise contributes to poor sleep. However, women may be more vulnerable to noise and hence more susceptible to sleep disruption-induced weight gain than men. In male rats, exposure to environmental (i.e. ambient) noise disrupts sleep and increases feeding and weight gain. However, the effects of environmental noise on sleep and weight gain in female rats are unknown. Thus, this study was designed to determine whether noise exposure would disturb sleep, increase feeding and weight gain and alter the length of the estrous cycle in female rats. SUBJECTS/METHODS: Female rats (12 weeks old) were exposed to noise for 17d (8 h/d during the light period) to determine the effects of noise on weight gain and food intake. In a separate set of females, estrous cycle phase and length, EEG, EMG, spontaneous physical activity and energy expenditure were recorded continuously for 27d during baseline (control, 9d), noise exposure (8 h/d, 9d) and recovery (9d) from sleep disruption. RESULTS: Noise exposure significantly increased weight gain and food intake compared to females that slept undisturbed. Noise also significantly increased wakefulness, reduced sleep and resulted in rebound sleep during the recovery period. Total energy expenditure was significantly lower during both noise exposure and recovery due to lower energy expenditure during spontaneous physical activity and sleep. Notably, noise did not alter the estrous cycle length. CONCLUSIONS: As previously observed in male rats, noise exposure disrupted sleep and increased weight gain in females but did not alter the length of the estrous cycle. This is the first demonstration of weight gain in female rats during sleep disruption. We conclude that the sleep disruption caused by exposure to environmental noise is a significant tool for determining how sleep loss contributes to obesity in females.

Orexin modulation of adipose tissue.

The orexins are neuropeptides with critical functions in the central nervous system. These neuropeptides have important roles in energy balance and obesity, and therefore on the accumulation of adipose tissue. Rodents lacking orexins, typically through genetic knockouts, experience increased weight gain and accumulation of adipose tissue. Evidence indicates that the lack of the orexins increase adiposity as a result of decreased energy expenditure, principally through a reduction of physical activity. Different lines of evidence suggest that other mechanisms are likely also in play, and neural influences on both white and brown adipose tissues remain to be fully and functionally defined. In addition, the orexin peptides and their receptors are expressed in adipose tissue, with little available information as to their significance. This review summarizes our current understanding of how the orexin peptides affect adipose tissue. We provide a brief introduction to the physiology of orexins and their effects on white and brown adipose tissues in the context of energy balance. We conclude this review by integrating this information in the context of the known physiology of the orexins. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

Methodological considerations for measuring spontaneous physical activity in rodents.

When exploring biological determinants of spontaneous physical activity (SPA), it is critical to consider whether methodological factors differentially affect rodents and the measured SPA. We determined whether acclimation time, sensory stimulation, vendor, or chamber size affected measures in rodents with varying propensity for SPA. We used principal component analysis to determine which SPA components (ambulatory and vertical counts, time in SPA, and distance traveled) best described the variability in SPA measurements. We compared radiotelemetry and infrared photobeams used to measure SPA and exploratory activity. Acclimation time, sensory stimulation, vendor, and chamber size independently influenced SPA, and the effect was moderated by the propensity for SPA. A 24-h acclimation period prior to SPA measurement was sufficient for habituation. Principal component analysis showed that ambulatory and vertical measurements of SPA describe different dimensions of the rodent's SPA behavior. Smaller testing chambers and a sensory attenuation cubicle around the chamber reduced SPA. SPA varies between rodents purchased from different vendors. Radiotelemetry and infrared photobeams differ in their sensitivity to detect phenotypic differences in SPA and exploratory activity. These data highlight methodological considerations in rodent SPA measurement and a need to standardize SPA methodology.

Role of the locus coeruleus in enhanced orexin A-induced spontaneous physical activity in obesity-resistant rats.

Orexin/hypocretin terminals innervate noradrenergic locus coeruleus (LC) neurons that project to the prefrontral cortex, which may influence spontaneous physical activity (SPA) and energy balance. Obesity-resistant (OR) rats have higher orexin receptors (OXR) mRNA in the LC and other brain regions, as well as lower adiposity compared with obese rats. These findings led us to hypothesize that orexin activity in the LC is relevant for the OR phenotype. We compared OR rats to Sprague-Dawley rats. We predicted that: 1) brain OXR expression pattern is sufficient to differentiate OR from non-bred Sprague-Dawley rats; 2) nonresting energy expenditure (NREE) and orexin A (OXA)-stimulated SPA after injection in LC would be greater in OR rats; and 3) the effect of OXA on SPA would be greater than its effect on feeding. OXR mRNA from 11 brain sites and the SPA and feeding responses to OXA in the LC were determined. Body composition, basal SPA, and EE were determined. Principal component analysis of the OXR expression pattern differentiates OR and Sprague-Dawley rats and suggests the OXR mRNA in the LC is important in defining the OR phenotype. Compared with Sprague-Dawley rats, OR rats had greater SPA and NREE and lower resting EE and adiposity. SPA responsivity to OXA in the LC was greater in OR rats compared with Sprague-Dawley rats. OXA in the LC did not stimulate feeding in OR or Sprague-Dawley rats. These data suggest that the LC is a prominent site modulating OXA-stimulated SPA, which promotes lower adiposity and higher nonresting EE.

Sleep loss in male rats contributes more to weight gain during sleep disruption than stress assessed by corticosterone.

Sleep disruption (SD) promotes stress which may mediate the effect of SD induced by noise on bodyweight gain and food intake. We determined if the change in bodyweight during SD caused by noise was driven by stress (assessed by corticosterone) and whether the effects of noise on SD, stress and bodyweight were specific to the method of SD or a consequence of SD per se. We isolated stress from SD due to noise by exposing rats to noise during the darkphase to test whether darkphase noise stimulated weight gain, stress and food intake. Male Sprague-Dawley rats slept undisturbed, were exposed to noise during both circadian phases (lightphase vs darkphase) and lightphase gentle handling. Bodyweight, food intake, physical activity, vigilance states, and plasma corticosterone were determined. Darkphase noise did not affect vigilance states. Unlike lightphase noise, darkphase noise and lightphase gentle handling did not stimulate weight gain or food intake. Only gentle handling significantly increased corticosterone levels. Noise during the lightphase increasesed weight gain and food intake by causing SD and these effects were not driven by stress as assessed by corticosterone. These results may have significant implications for developing translational models of insomnia-induced obesity in humans.

Corrigendum: Impact of short and long exposure to cafeteria diet on food intake and white adipose tissue lipolysis mediated by glucagon-like peptide 1 receptor.

[This corrects the article DOI: 10.3389/fendo.2023.1164047.].

Impact of short and long exposure to cafeteria diet on food intake and white adipose tissue lipolysis mediated by glucagon-like peptide 1 receptor.

Introduction: The modern food environment facilitates excessive calorie intake, a major driver of obesity. Glucagon-like peptide 1 (GLP1) is a neuroendocrine peptide that has been the basis for developing new pharmacotherapies against obesity. The GLP1 receptor (GLP1R) is expressed in central and peripheral tissues, and activation of GLP1R reduces food intake, increases the expression of thermogenic proteins in brown adipose tissue (BAT), and enhances lipolysis in white adipose tissue (WAT). Obesity decreases the efficiency of GLP1R agonists in reducing food intake and body weight. Still, whether palatable food intake before or during the early development of obesity reduces the effects of GLP1R agonists on food intake and adipose tissue metabolism remains undetermined. Further, whether GLP1R expressed in WAT contributes to these effects is unclear. Methods: Food intake, expression of thermogenic BAT proteins, and WAT lipolysis were measured after central or peripheral administration of Exendin-4 (EX4), a GLP1R agonist, to mice under intermittent-short exposure to CAF diet (3 h/d for 8 days) or a longer-continuous exposure to CAF diet (24 h/d for 15 days). Ex-vivo lipolysis was measured after EX4 exposure to WAT samples from mice fed CAF or control diet for 12 weeks. . Results: During intermittent-short exposure to CAF diet (3 h/d for 8 days), third ventricle injection (ICV) and intra-peritoneal administration of EX4 reduced palatable food intake. Yet, during a longer-continuous exposure to CAF diet (24 h/d for 15 days), only ICV EX4 administration reduced food intake and body weight. However, this exposure to CAF diet blocked the increase in uncoupling protein 1 (UCP1) caused by ICV EX4 administration in mice fed control diet. Finally, GLP1R expression in WAT was minimal, and EX4 failed to increase lipolysis ex-vivo in WAT tissue samples from mice fed CAF or control diet for 12 weeks. . Discussion: Exposure to a CAF diet during the early stages of obesity reduces the effects of peripheral and central GLP1R agonists, and WAT does not express a functional GLP1 receptor. These data support that exposure to the obesogenic food environment, without the development or manifestation of obesity, can alter the response to GLP1R agonists. .

Behavioral responses to orexin, orexin receptor gene expression, and spontaneous physical activity contribute to individual sensitivity to obesity.

There is significant variability in diet-induced obesity (DIO) among humans and rodents, which has been associated with differences in intrinsic spontaneous physical activity (SPA). The orexin neuropeptides positively modulate SPA through multiple brain sites, but the effects of DIO on orexin's activity are not well understood. In this study, we tested the hypothesis that DIO sensitivity is mediated by decreased SPA and changes in the function of the orexins. As a DIO model, we used male Sprague-Dawley rats fed a high-fat (HF; 45% kcal from fat) or a low-fat (LF; 10% kcal from fat) diet for 10 wk. We measured SPA before and after HF or LF feeding and expression of orexin receptors by real-time PCR after dietary treatments. We tested DIO effects on orexin signaling by measuring SPA after injection of orexin A in the rostral lateral hypothalamus (RLH) before and after 10 wk of HF feeding. Finally, we tested whether daily orexin A RLH injections prevent DIO caused by HF feeding. Our results show that resistance to DIO is associated with an increase in SPA, SPA after injection of orexin A in RLH, and orexin receptor expression in sites that mediate orexin's effect on SPA, including RLH. We show that daily injections of orexin peptide in RLH prevent DIO without altering food intake. We estimate that the energetic cost of SPA after orexin A RLH injection accounts for approximately 61% of the extra caloric intake associated with HF intake, suggesting additional effects of orexins. In summary, our results suggest that variability in DIO sensitivity is mediated through adaptations in the activity of the orexin peptides and their receptors.

Eating contexts determine the efficacy of nutrient warning labels to promote healthy food choices.

Introduction: Unhealthy food choices increase the risk of obesity and its co-morbidities. Nutrition labels are a public health policy that aims to drive individuals toward healthier food choices. Chile has been an example of this policy, where mandatory nutrient warning labels (NWL) identify processed foods high in calories and critical nutrients. Eating contexts influence individual food choices, but whether eating contexts also influence how NWL alter the decision process and selection during food choice is unknown. Methods: In an online mouse-tracking study, participants prompted to health, typical, or unrestricted eating contexts were instructed to choose between pairs of foods in the presence or absence of NWL. Conflict during choices was analyzed using mouse paths and reaction times. Results: NWL increased conflict during unhealthy food choices and reduced conflict during healthy choices in all contexts. However, the probability that NWL reversed an unhealthy choice was 80% in a healthy, 37% in a typical, and 19% in an unrestricted context. A drift-diffusion model analysis showed the effects of NWL on choice were associated with an increased bias toward healthier foods in the healthy and typical but not in the unrestricted context. Discussion: These data suggest that the efficacy of NWL to drive healthy food choices increases in a healthy eating context, whereas NWL are less effective in typical or unrestricted eating contexts.

Intrinsic phototransduction persists in melanopsin-expressing ganglion cells lacking diacylglycerol-sensitive TRPC subunits.

In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate various non-image-forming photic responses, such as circadian photoentrainment, pupillary light reflex and pineal melatonin suppression. ipRGCs directly respond to environmental light by activation of the photopigment melanopsin followed by the opening of an unidentified cation-selective channel. Studies in heterologous expression systems and in the native retina have strongly implicated diacylglycerol-sensitive transient receptor potential channels containing TRPC3, TRPC6 and TRPC7 subunits in melanopsin-evoked depolarization. Here we show that melanopsin-evoked electrical responses largely persist in ipRGCs recorded from early postnatal (P6-P8) and adult (P22-P50) mice lacking expression of functional TRPC3, TRPC6 or TRPC7 subunits. Multielectrode array (MEA) recordings performed at P6-P8 stages under conditions that prevent influences from rod/cone photoreceptors show comparable light sensitivity for the melanopsin-evoked responses in these mutant mouse lines in comparison to wild-type (WT) mice. Patch-clamp recordings from adult mouse ipRGCs lacking TRPC3 or TRPC7 subunits show intrinsic light-evoked responses equivalent to those recorded in WT mice. Persistence of intrinsic light-evoked responses was also noted in ipRGCs lacking TRPC6 subunits, although with significantly smaller magnitudes. These results demonstrate that the melanopsin-evoked depolarization in ipRGCs is not mediated by either TRPC3, TRPC6 or TRPC7 channel subunits alone. They also suggest that the melanopsin signaling pathway includes TRPC6-containing heteromeric channels in mature retinas.

Impact of Gut and Metabolic Hormones on Feeding Reward.

Ingestion of food activates a cascade of endocrine responses (thereby reflecting a contemporaneous feeding status) that include the release of hormones from the gastrointestinal (GI) tract, such as cholecystokinin (CCK), glucagonlike peptide YY (PYY), peptide PP, and oleoylethanolamide, as well as suppression of ghrelin secretion. The pancreas and adipose tissue, on the other hand, release hormones that serve as a measure of the current metabolic state or the long-term energy stores, that is, insulin, leptin, and adiponectin. It is well known and intuitively understandable that these hormones target either directly (by crossing the blood-brain barrier) or indirectly (e.g., via vagal input) the "homeostatic" brainstem-hypothalamic pathways involved in the regulation of appetite. The current article focuses on yet another target of the metabolic and GI hormones that is critical in inducing changes in food intake, namely, the reward system. We discuss the physiological basis of this functional interaction, its importance in the control of appetite, and the impact that disruption of this crosstalk has on energy intake in select physiological and pathophysiological states. We conclude that metabolic and GI hormones have a capacity to strengthen or weaken a response of the reward system to a given food, and thus, they are fundamental in ensuring that feeding reward is plastic and dependent on the energy status of the organism. © 2021 American Physiological Society. Compr Physiol 11:1425-1447, 2021.

Spontaneous Physical Activity Defends Against Obesity.

PURPOSE OF REVIEW: Spontaneous physical activity (SPA) is a physical activity not motivated by a rewarding goal, such as that associated with food-seeking or wheel-running behavior. SPA is often thought of as only "fidgeting," but that is a mischaracterization, since fidgety behavior can be linked to stereotypies in neurodegenerative disease and other movement disorders. Instead, SPA should be thought of as all physical activity behavior that emanates from an unconscious drive for movement. RECENT FINDINGS: An example of this may be restless behavior, which can include fidgeting and gesticulating, frequent sit-to-stand movement, and more time spent standing and moving. All physical activity burns calories, and as such, SPA could be manipulated as a means to burn calories, and defend against weight gain and reduce excess adiposity. In this review, we discuss human and animal literature on the use of SPA in reducing weight gain, the neuromodulators that could be targeted to this end, and future directions in this field.

Role of Sex and the Environment in Moderating Weight Gain Due to Inadequate Sleep.

PURPOSE OF REVIEW: The growing prevalence of obesity, inadequate sleep and sleep disorders together with the negative impact of lack of sleep on overall health highlights the need for therapies targeted towards weight gain due to sleep loss. RECENT FINDINGS: Sex disparities in obesity and sleep disorders are present; yet, the role of sex is inadequately addressed and thus it is unclear whether sensitivity to sleep disruption differs between men and women. Like sex, environmental factors contribute to the development of obesity and poor sleep. The obesogenic environment is characterized by easy access to palatable foods and a low demand for energy expenditure in daily activities. These and other environmental factors are discussed, as they drive altered sleep or their interaction with food choice and intake can promote obesity. We discuss data that suggest differences in sleep patterns and responses to sleep disruption influence sex disparities in weight gain, and that enviromental disturbances alter sleep and interact with features of the obesogenic environment that together promote obesity.

Promotion of Wakefulness and Energy Expenditure by Orexin-A in the Ventrolateral Preoptic Area.

STUDY OBJECTIVES: The ventrolateral preoptic area (VLPO) and the orexin/hypocretin neuronal system are key regulators of sleep onset, transitions between vigilance states, and energy homeostasis. Reciprocal projections exist between the VLPO and orexin/hypocretin neurons. Although the importance of the VLPO to sleep regulation is clear, it is unknown whether VLPO neurons are involved in energy balance. The purpose of these studies was to determine if the VLPO is a site of action for orexin-A, and which orexin receptor subtype(s) would mediate these effects of orexin-A. We hypothesized that orexin-A in the VLPO modulates behaviors (sleep and wakefulness, feeding, spontaneous physical activity [SPA]) to increase energy expenditure. DESIGN AND MEASUREMENTS: Sleep, wakefulness, SPA, feeding, and energy expenditure were determined after orexin-A microinjection in the VLPO of male Sprague-Dawley rats with unilateral cannulae targeting the VLPO. We also tested whether pretreatment with a dual orexin receptor antagonist (DORA, TCS-1102) or an OX2R antagonist (JNJ-10397049) blocked the effects of orexin-A on the sleep/wake cycle or SPA, respectively. RESULTS: Orexin-A injected into the VLPO significantly increased wakefulness, SPA, and energy expenditure (SPA-induced and total) and reduced NREM sleep and REM sleep with no effect on food intake. Pretreatment with DORA blocked the increase in wakefulness and the reduction in NREM sleep elicited by orexin-A, and the OX2R antagonist reduced SPA stimulated by orexin-A. CONCLUSIONS: These data show the ventrolateral preoptic area is a site of action for orexin-A, which may promote negative energy balance by modulating sleep/wakefulness and stimulating spontaneous physical activity and energy expenditure.

Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats.

Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement may promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest that the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN.

High and low activity rats: elevated intrinsic physical activity drives resistance to diet-induced obesity in non-bred rats.

OBJECTIVE: Humans and rodents show large variability in their individual sensitivity to diet-induced obesity (DIO), which has been associated with differences in intrinsic spontaneous physical activity (SPA). Evidence from genetic and out-bred rat obesity models shows that higher activity of the orexin peptides results in higher intrinsic SPA and protection against DIO. Based on this, we hypothesized that naturally occurring variation in SPA and orexin signaling is sufficient to drive differences in sensitivity to DIO. DESIGN AND METHODS: Orexin expression, behavioral responses to orexin-A, basal energy expenditure and sensitivity to DIO were measured in in non-manipulated male Sprague-Dawley rats selected for high and low intrinsic SPA. RESULTS: Male Sprague-Dawley rats were classified as high-activity or low-activity based on differences in intrinsic SPA. High-activity rats showed higher expression of prepro-orexin mRNA, higher sensitivity to behavioral effects of orexin injection, higher basal energy expenditure and were more resistant to obesity caused by high-fat diet consumption than low-activity rats. CONCLUSION: Our results define a new model of differential DIO sensitivity, the high-activity and low-activity rats, and suggest that naturally occurring variations in intrinsic SPA cause differences in energy expenditure that are mediated by orexin signaling and alter DIO sensitivity.