Cumulative effect of obesity phenotypes on body weight and body mass index.

BACKGROUND: Obesity originates from an imbalance between energy intake and expenditure. Changes in energy intake components (satiation, postprandial satiety, emotional eating) and energy expenditure have been linked to obesity and are referred to as obesity phenotypes. We aim to study if these obesity phenotypes have a cumulative effect on body weight and body mass index (BMI). SUBJECT/METHODS: This is a cross-sectional study of adult patients with obesity (BMI > 30 kg/m2) who completed the validated tests to measure the obesity phenotypes. A total of 464 were included in this study. INTERVENTIONS/METHODS: We defined higher calories to fullness during an ad libitum meal as abnormal satiation, accelerated time to half gastric emptying with scintigraphy as abnormal postprandial satiety, higher anxiety score on the Hospital Anxiety and Depression Scale as hedonic eating behavior, and decreased percentage of measured resting energy expenditure as abnormal energy expenditure. The primary analysis was done on the number of phenotypes ( ≤ 1 and ≥ 2) with body weight and BMI using an independent t-test. RESULTS: Our cohort included 464 patients (mean [SD] age 42.0 [10.9] years, 79% females, weight 111.2 [22.9] kg, BMI 38.9 [7.0] kg/m2). There were 294 patients who had ≤ 1 phenotype, and 170 patients with ≥ 2 phenotypes with no baseline demographical differences (i.e., age and sex). Having ≥ 2 phenotypes was associated with higher body weight (115 [25] kg vs. 109 [21] kg; p = 0.004), BMI (40 [8] kg/m2 vs. 38 [7] kg/m2; p = 0.02) and waist (118 [15] cm vs. 115 [13] cm; p = 0.04) and hip (129 [14] cm vs. 125 [13] cm; p = 0.01) circumferences compared to ≤ 1 phenotype. CONCLUSION: Obesity phenotypes are associated with an additive effect on the body weight and BMI. Patients who have multiple obesity phenotypes may require a more aggressive approach to enhance weight loss.

Meal related symptoms in youth with chronic abdominal pain: Relationship to anxiety, depression, and sleep dysfunction.

OBJECTIVE: The objective of the current study was to describe meal-related symptoms in youth with chronic abdominal pain fulfilling criteria for a disorder of gut-brain interaction (DGBI) and their associations with anxiety, depression, and sleep disturbances. METHODS: This was a retrospective evaluation of 226 consecutive patients diagnosed with an abdominal pain-associated DGBI. As part of routine care, all had completed a standardized symptom history, the Sleep Disturbances Scale for Children (utilized to assess for disorders of initiation and maintenance of sleep and excessive daytime somnolence) and the Behavior Assessment System for Children-Third Edition (utilized to assess for anxiety and depression). Four meal related symptoms were assessed: early satiety, postprandial bloating, postprandial abdominal pain, and postprandial nausea. RESULTS: Overall, 87.6% of patients reported at least one meal related symptom and the majority reported at least three symptoms. All meal related symptoms were significantly related to each other. Postprandial pain and nausea were more often reported by females. Early satiety, postprandial bloating, and postprandial nausea, but not postprandial pain demonstrated significant though variable associations with anxiety, depression, disorders of initiation and maintenance of sleep, and disorders of excessive somnolence, but only in adolescents. CONCLUSIONS: Meal related symptoms are very common in youth with abdominal pain-associated DGBIs. Early satiety, bloating, and postprandial nausea demonstrate variable associations with anxiety, depression, and disordered sleep while increased postprandial pain was not associated with psychologic or sleep dysfunction, suggesting a different pathway for symptom generation.

Meat- and plant-based products induced similar satiation which was not affected by multimodal augmentation.

Little is known about how plant-based products influence satiation compared to corresponding meat-based products. As augmented reality (AR) intensifies sensory experiences, it was hypothesized to improve satiation. This study compared satiation between intake of meatballs and plant-based balls and plant-based balls intensified with AR for visual, olfactory, and haptic sensory properties. Intake order of the meatballs, plant-based balls, and augmented plant-based balls, eaten on separate days, was randomized. Satiation was measured from twenty-eight non-obese adults as ad libitum intake of the balls and extra snacks, and as subjective appetite sensations. Liking and wanting to eat the products were also investigated. There were no differences between the products in satiation. Before tasting the augmented plant-based balls were less liked than the meatballs (p = 0.002) or plant-based balls (p = 0.046), but after eating the first ball or eating the ad libitum number of balls the differences in liking disappeared. Wanting evaluations were similar for each product and decreased during eating (p < 0.001). A group of participants susceptible to AR was found (n = 11), described by decreased intake when augmentation was applied. Among the sub-group, wanting to eat the augmented balls was lower before tasting (p = 0.019) and after eating the first ball (p = 0.002) and appetite was less suppressed after eating the balls ad libitum (p = 0.01), when compared to non-susceptible participants. We conclude that meatballs and plant-based balls were equal in inducing satiation, and multisensory augmentation did not influence satiation. However, the augmentation decreased liking evaluations before tasting. Further studies are needed to explore differences between consumer groups in susceptibility to augmentation.

Neural circuits regulation of satiation.

Terminating a meal after achieving satiation is a critical step in maintaining a healthy energy balance. Despite the extensive collection of information over the last few decades regarding the neural mechanisms controlling overall eating, the mechanism underlying different temporal phases of eating behaviors, especially satiation, remains incompletely understood and is typically embedded in studies that measure the total amount of food intake. In this review, we summarize the neural circuits that detect and integrate satiation signals to suppress appetite, from interoceptive sensory inputs to the final motor outputs. Due to the well-established role of cholecystokinin (CCK) in regulating the satiation, we focus on the neural circuits that are involved in regulating the satiation effect caused by CCK. We also discuss several general principles of how these neural circuits control satiation, as well as the limitations of our current understanding of the circuits function. With the application of new techniques involving sophisticated cell-type-specific manipulation and mapping, as well as real-time recordings, it is now possible to gain a better understanding of the mechanisms specifically underlying satiation.

Associations between sleep and appetitive traits in higher-income preschoolers: A six-month study.

BACKGROUND: Short sleep is consistently linked with childhood obesity, possibly via disrupting appetite hormones and increasing food responsiveness. Few studies have objectively examined this association in early childhood. OBJECTIVE: To evaluate associations of sleep quantity and quality with child appetitive traits and eating in the absence of hunger (EAH) in a higher-income cohort of 86 preschool-age children (age 4.0 ± 0.8 years; 42% female; 93% non-Hispanic white, Northern New England, US). METHODS: Children's sleep duration and quality were assessed via parent report (Children's Sleep Habits Questionnaire, CSHQ) at baseline and 6-month follow-up and via accelerometry at baseline. Parents also completed the Child Eating Behaviors Questionnaire to assess the child's appetitive traits. EAH, an objective measure of overeating, was observed at baseline during an in-person visit. Associations between sleep measures and appetitive traits were examined with linear mixed-effect or linear regression models, as appropriate, adjusting for child age, sex, and household income. RESULTS: Shorter sleep duration per parent report was associated with less satiety responsiveness (standardized ß = 0.14, 95% CI: 0.01, 0.26; p = 0.03). Further, satiety responsiveness was inversely related to EAH (Pearson's r = -0.35, p = 0.02). No associations were found between accelerometer-measured sleep parameters and appetitive traits, and no sleep measures were related to EAH. CONCLUSIONS: Shorter usual sleep, per the parent report, was cross-sectionally associated with reduced satiety responsiveness in this sample of higher-income preschoolers. Future studies should consider whether socioeconomic status may modify the impact of poor sleep on appetitive traits in early childhood.

Not feeling the heat? Effects of dietary protein on satiation and satiety in mice are not due to its impact on body temperature.

Dietary protein modulates food intake (FI) via unclear mechanism(s). One possibility is that higher protein leads to greater post-ingestive heat production (Specific dynamic action: SDA) leading to earlier meal termination (increased satiation), and inhibition of further intake (increased satiety). The influence of dietary protein on feeding behaviour in C57BL/6J mice was tested using an automated FI monitoring system (BioDAQ), simultaneous to body temperature (Tb). Total FI, inter meal intervals (IMI, satiety) and meal size (MS, satiation) were related to changes in Tb after consuming low (5%, LP), moderate (15%, MP) and high (30%, HP) protein diets. Diets were tested over three conditions: 1) room temperature (RT, 21 ± 1 °C), 2) room temperature and running wheels (RTRW) and 3) low temperature (10 °C) and running wheels (LTRW). The differences between diets and conditions were also compared using mixed models. Mice housed at RT fed HP diet, reduced total FI compared with LP and MP due to earlier meal termination (satiation effect). FI was lowered in RTRW conditions with no differences between diets. FI significantly increased under LTRW conditions for all diets, with protein content leading to earlier meal termination (satiation) but not the intervals between feeding bouts (satiety). Tb fell immediately after feeding in all conditions. Despite a reduction in total FI in mice fed HP, mediated via increased satiation, this effect was not linked to increased Tb during meals. We conclude effects of dietary protein on intake are not mediated via SDA and Tb.

Individual variability and consistency of post-exercise energy and macronutrient intake, appetite sensations, and food reward in healthy adults.

Limited evidence is available about the variability of appetitive responses within individuals after an acute bout of exercise. The present study aimed to assess the consistency and individual variability of post-exercise appetitive responses in healthy individuals. Twenty participants (10 females, 23.9 ± 4.1 years, 22.5 ± 2.0 kg m-2) joined the laboratory to perform four sessions separated by a minimum of 5 days: i) a control session with a rest period before and an ad libitum lunch (REST), and ii) three identical exercise sessions (EX) with a 30-min moderate-intensity (60-70% of predicted maximal heart rate) walking bout ending 25 min before the ad libitum lunch. Subjective appetite sensations were assessed before and after the meal at regular intervals, and satiety quotients were calculated. Food reward was assessed by the Leeds Food Preference Questionnaire before and after lunch. For each EX session, the difference with the REST session was calculated (Δ = EX - REST). Energy and macronutrient intake were consistent in response to exercise (all intraclass correlation coefficients (ICC) > 0.8) while results showed that post-exercise subjective appetite sensations and satiety quotients varied across the three EX sessions (almost all ICC < 0.7). Food reward was overall consistent in response to exercise before the test meal but not after. When considering the changes (Δ), the results showed no or poor consistency for most of the appetitive outcomes. To conclude, energy and macronutrient intake, as well as pre-meal food reward, are consistent after exercise in healthy individuals, while subjective appetite sensations are not stable within individuals across the sessions. Regarding the variations from REST to EX sessions, the results suggest that the individual changes observed are only random day-to-day variations.

Appetite, food intake, and gut hormone responses to glycomacropeptide protein ingestion in older adults: A feasibility, acceptability, and pilot study.

Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.

The effects of a fibre-enriched bakery product on glucose, insulin values and appetite. A pilot randomised cross-over trial.

Brewers spent grain (BSG) is a valuable source of arabinoxylans with potential beneficial effects on glucose values. This pilot randomised crossover double-blind trial compared the effects of panettone, a sweet baked-product, enriched with BSG-fibre (p-rich) to unenriched panettone (p-standard) on glucose and insulin blood values and appetite scores. Ten healthy volunteers consumed each food in a random order. Blood variables and appetite scores were assessed at fasting and at different intervals after each food consumption. Glucose values were significantly higher after p-standard intake at 90-min (89.9 ± 16.1 vs 74.6 ± 19.4 mg/dL) and 120-min (81.1 ± 9.85 vs 72.1 ± 14.0 mg/dL). The areas-under-the-curve (AUCs) were lower for both glucose (p = .043) and insulin values (p = .036) with p-rich. At 240-min, satiety was higher (p = .006), and desire-to-eat lower (p = .008) with p-rich; desire-to-eat AUC was lower with p-rich too (p = .029). The integration of a small amount of BSG-derived fibre into a sweet food led to improved glycaemic control and appetite regulation.

Effects of hunger and calorie content on visual awareness of food stimuli.

Calorie content and hunger are two fundamental cues acting upon the processing of visually presented food items. However, whether and to which extent they affect visual awareness is still an open question. Here, high- and low-calorie food images administered to hungry or satiated participants were confronted in a breaking-Continuous Flash Suppression paradigm (Experiment 1), measuring the time required to access to visual awareness, and in a Binocular Rivalry paradigm (Experiment 2), quantifying the dominance time in visual awareness. Experiment 1 showed that high-calorie food accessed faster visual awareness, but mostly in satiated participants. Experiment 2 indicated that high-calorie food dominated longer visual awareness, regardless the degree of hunger. We argued that the unconscious advantage (Experiment 1) would represent a default state of the visual system towards highest-energy nutrients, yet the advantage is lost in hunger so to be tuned towards an increased need for any nutritional category. On the other hand, the conscious advantage of high-calorie food (Experiment 2) would represent a conscious perceptual and attentional bias towards highest energy-dense food useful for the actual detection of these stimuli in the environment.

Neuroscience of eating: Pace and portion control.

Satiety-promoting neurons of the hindbrain have long been known for their role in meal termination. An innovative new study now reveals how different hindbrain cell types mediate appetite on distinct timescales.

Oxytocin-receptor-expressing neurons in the lateral parabrachial nucleus activate widespread brain regions predominantly involved in fluid satiation.

Fluid satiation is an important signal and aspect of body fluid homeostasis. Oxytocin-receptor-expressing neurons (OxtrPBN) in the dorsolateral subdivision of the lateral parabrachial nucleus (dl LPBN) are key neurons which regulate fluid satiation. In the present study, we investigated brain regions activated by stimulation of OxtrPBN neurons in order to better characterise the fluid satiation neurocircuitry in mice. Chemogenetic activation of OxtrPBN neurons increased Fos expression (a proxy marker for neuronal activation) in known fluid-regulating brain nuclei, as well as other regions that have unclear links to fluid regulation and which are likely involved in regulating other functions such as arousal and stress relief. In addition, we analysed and compared Fos expression patterns between chemogenetically-activated fluid satiation and physiological-induced fluid satiation. Both models of fluid satiation activated similar brain regions, suggesting that the chemogenetic model of stimulating OxtrPBN neurons is a relevant model of physiological fluid satiation. A deeper understanding of this neural circuit may lead to novel molecular targets and creation of therapeutic agents to treat fluid-related disorders.

Evolutionary perspectives on substance and behavioural addictions: Distinct and shared pathways to understanding, prediction and prevention.

Addiction poses significant social, health, and criminal issues. Its moderate heritability and early-life impact, affecting reproductive success, poses an evolutionary paradox: why are humans predisposed to addictive behaviours? This paper reviews biological and psychological mechanisms of substance and behavioural addictions, exploring evolutionary explanations for the origin and function of relevant systems. Ancestrally, addiction-related systems promoted fitness through reward-seeking, and possibly self-medication. Today, psychoactive substances disrupt these systems, leading individuals to neglect essential life goals for immediate satisfaction. Behavioural addictions (e.g. video games, social media) often emulate ancestrally beneficial behaviours, making them appealing yet often irrelevant to contemporary success. Evolutionary insights have implications for how addiction is criminalised and stigmatised, propose novel avenues for interventions, anticipate new sources of addiction from emerging technologies such as AI. The emerging potential of glucagon-like peptide 1 (GLP-1) agonists targeting obesity suggest the satiation system may be a natural counter to overactivation of the reward system.

Impact of Substituting Meats with Plant-Based Analogues on Health-Related Markers: A Systematic Review of Human Intervention Studies.

The growing drive towards more sustainable dietary patterns has led to an increased demand for and availability of plant-based meat analogues (PBMAs). This systematic review aims to summarize the currently available evidence from human intervention studies investigating the impact of substituting animal meat (AM) with PBMAs in adults. A total of 19 studies were included. Overall, an increase in satiety following PBMA intake was reported, albeit to different extents and not always accompanied by changes in leptin and ghrelin. PBMAs generally resulted in lower protein bioavailability and a smaller increase in plasma essential amino acids in comparison to AM. However, muscle protein synthesis and physical performance were not affected. Finally, conflicting results have been reported for other outcomes, such as pancreatic and gastrointestinal hormones, oxidative stress and inflammation, vascular function, and microbiota composition. In conclusion, we documented that the impact of substituting AM with PBMA products has been scarcely investigated. In addition, the heterogeneity found in terms of study design, population, outcomes, and findings suggests the need for additional high-quality intervention trials, particularly long-term ones, to better clarify the advantages and potential critical issues of such substitutions within sustainable healthy diets.

Hunger and satiety: Neuronal dynamics in Hydra behavior.

Hormonal and neuronal inputs to the brain control how much animals eat. The origins of this behavior were unclear, but in this issue of Cell Reports, Giez et al.1 describe specific neurons inhibiting feeding in evolutionary ancient animals without brain.

Examining the Direct and Indirect Effects of Postprandial Amino Acid Responses on Markers of Satiety following the Acute Consumption of Lean Beef-Rich Meals in Healthy Women with Overweight.

The consumption of protein-rich foods stimulates satiety more than other macronutrient-rich foods; however, the underlying mechanisms-of-action are not well-characterized. The objective of this study was to identify the direct and indirect effects of postprandial amino acid (AA) responses on satiety. Seventeen women (mean ± SEM, age: 33 ± 1 year; BMI: 27.8 ± 0.1 kg/m2) consumed a eucaloric, plant-based diet containing two servings of lean beef/day (i.e., 7.5 oz (207 g)) for 7 days. During day 6, the participants completed a 12 h controlled-feeding, clinical testing day including repeated satiety questionnaires and blood sampling to assess pre- and postprandial plasma AAs, PYY, and GLP-1. Regression and mediation analyses were completed to assess AA predictors and hormonal mediators. Total plasma AAs explained 41.1% of the variance in perceived daily fullness (p < 0.001), 61.0% in PYY (p < 0.001), and 66.1% in GLP-1 (p < 0.001) concentrations, respectively. Several individual AAs significantly predicted fluctuations in daily fullness, PYY, and GLP-1. In completing mediation analyses, the effect of plasma leucine on daily fullness was fully mediated by circulating PYY concentrations (indirect effect = B: 0.09 [Boot 95% CI: 0.032, 0.17]) as no leucine-fullness direct effect was observed. No other mediators were identified. Although a number of circulating AAs predict satiety, leucine was found to do so through changes in PYY concentrations in middle-aged women.

Effects of sleep deprivation on food-related Pavlovian-instrumental transfer: a randomized crossover experiment.

Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals-sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating.

Volitionally Regulated Breathing with Prolonged Expiration Influences Food Craving and Impulsivity.

INTRODUCTION: Previously, an intervention involving volitional slow breathing reduced trait food craving with protective effects on cardiac vagal activity (CVA). Breathing with a low inspiration-to-expiration (i/e) ratio also increases CVA. High CVA was separately associated with low unregulated eating and lesser impulsivity. Hence, the present study assessed breathing with a low i/e for effects on state food craving, hunger and satiety, state impulsivity, and heart rate variability (HRV) in healthy obese persons. METHODS: Forty obese persons were randomized to two groups. The intervention group (mean age ± SD, 41.15 ± 12.63, M:F, 10:10) practiced metronome-regulated breathing with low i/e at 12 breaths per minute (expiration 72% of total breath duration) and attained expiration 55.8% of total breath duration, while the active control group (mean age ± SD, 44.45 ± 11.06, M:F, 13:07) sat motionless and directed their gaze and awareness to the stationary metronome without modifying their breath consciously. The HRV was recorded before, during, and after breathing intervention (or control) (standard limb lead I, acquisition at 2,000 Hz, with an LF filter = 0.5 Hz and HF filter = 50 Hz). Time-domain and frequency-domain HRV parameters were obtained with Kubios software. State food craving, and hunger and satiety were recorded before and after the intervention/control. RESULTS: The intervention group decreased total state food craving scores and the sub-domains (i.e., desire to eat, positive reinforcement, lack of control and hunger), increased current satisfaction with food, decreased total state impulsivity (repeated measures ANOVA, p < 0.05 in all cases), increased HF-HRV and RMSSD (linear mixed model analyses with age and gender as fixed factors; p < 0.05 in all cases) during the intervention compared to the preceding baseline. The intervention group also showed an increase in positive mood and a decrease in aroused and negative mood states. CONCLUSION: Changes in state food craving and impulsivity could be related to an increase in HRV or to changes in subjective relaxation and positive mood or to both.

Could Insulin Be a Better Regulator of Appetite/Satiety Balance and Body Weight Maintenance in Response to Glucose Exposure Compared to Sucrose Substitutes? Unraveling Current Knowledge and Searching for More Appropriate Choices.

BACKGROUND: Insulin exerts a crucial impact on glucose control, cellular growing, function, and metabolism. It is partially modulated by nutrients, especially as a response to the intake of foods, including carbohydrates. Moreover, insulin can exert an anorexigenic effect when inserted into the hypothalamus of the brain, in which a complex network of an appetite/hunger control system occurs. The current literature review aims at thoroughly summarizing and scrutinizing whether insulin release in response to glucose exposure may be a better choice to control body weight gain and related diseases compared to the use of sucrose substitutes (SSs) in combination with a long-term, well-balanced diet. METHODS: This is a comprehensive literature review, which was performed through searching in-depth for the most accurate scientific databases and applying effective and relevant keywords. RESULTS: The insulin action can be inserted into the hypothalamic orexigenic/anorexigenic complex system, activating several anorexigenic peptides, increasing the hedonic aspect of food intake, and effectively controlling the human body weight. In contrast, SSs appear not to affect the orexigenic/anorexigenic complex system, resulting in more cases of uncontrolled body weight maintenance while also increasing the risk of developing related diseases. CONCLUSIONS: Most evidence, mainly derived from in vitro and in vivo animal studies, has reinforced the insulin anorexigenic action in the hypothalamus of the brain. Simultaneously, most available clinical studies showed that SSs during a well-balanced diet either maintain or even increase body weight, which may indirectly be ascribed to the fact that they cannot cover the hedonic aspect of food intake. However, there is a strong demand for long-term longitudinal surveys to effectively specify the impact of SSs on human metabolic health.

Fluid transitions.

Water is critical for survival and thirst is a powerful way of ensuring that fluid levels remain in balance. Overconsumption, however, can have deleterious effects, therefore optimization requires a need to balance the drive for water with the satiation of that water drive. This review will highlight our current understanding of how thirst is both generated and quenched, with particular focus on the roles of angiotensin II, glucagon like-peptide 1, and estradiol in turning on and off the thirst drive. Our understanding of the roles these bioregulators play has benefited from modern behavioral analyses, which have improved the time resolution of intake measures, allowing for attention to the details of the patterns within a bout of intake. This has led to behavioral interpretation in ways that are helpful in understanding the many controls of water intake and has expanded our understanding beyond the dichotomy that something which increases water intake is simply a "stimulator" while something that decreases water intake is simply a "satiety" factor. Synthesizing the available information, we describe a framework in which thirst is driven directly by perturbations in fluid intake and indirectly modified by several bioregulators. This allows us to better highlight areas that are in need of additional attention to form a more comprehensive understanding of how the system transitions between states of thirst and satiety.