Beyond appetite regulation: Targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss.

New appetite-regulating antiobesity treatments such as semaglutide and agents under investigation such as tirzepatide show promise in achieving weight loss of 15% or more. Energy expenditure, fat oxidation, and lean mass preservation are important determinants of weight loss and weight-loss maintenance beyond appetite regulation. This review discusses prior failures in clinical development of weight-loss drugs targeting energy expenditure and explores novel strategies for targeting energy expenditure: mitochondrial proton leak, uncoupling, dynamics, and biogenesis; futile calcium and substrate cycling; leptin for weight maintenance; increased sympathetic nervous system activity; and browning of white fat. Relevant targets for preserving lean mass are also reviewed: growth hormone, activin type II receptor inhibition, and urocortin 2 and 3. We endorse moderate modulation of energy expenditure and preservation of lean mass in combination with efficient appetite reduction as a means of obtaining a significant, safe, and long-lasting weight loss. Furthermore, we suggest that the regulatory guidelines should be revisited to focus more on the quality of weight loss and its maintenance rather than the absolute weight loss. Commitment to this research focus both from a scientific and from a regulatory point of view could signal the beginning of the next era in obesity therapies.

A review on differential effects of dietary fatty acids on weight, appetite and energy expenditure.

The association between weight and chronic diseases is well defined. The quality and quantity of dietary fatty acids is an important external factor and appetite and energy expenditure, are important internal factors in determining body weight. On the other hand, dietary fatty acids composition can modulate appetite and energy metabolism, but not all fats are equal in producing metabolic responses.Given the accumulating evidence for differential effects of various dietary fatty acids, one important area of investigation is to scrutinize their roles in weight, appetite and energy expenditure modulation. There is substantial evidence to suggest that saturated fatty acids have a greater effect on appetite control, although in the long run may result in more weight gain than unsaturated fatty acids due to a weaker stimulation of energy expenditure. In contrast, mono-unsaturated fats do not have much effects on appetite control, but they can be beneficial in weight control over the long term due to stimulatory effects on energy expenditure. Interestingly, in case of poly unsaturated fats, including n-3 and n-6, their effect on increasing energy expenditure is aligned, but they act differently in controlling weight and appetite.

Nicotine and energy balance: A review examining the effect of nicotine on hormonal appetite regulation and energy expenditure.

Nicotine has been shown to decrease appetite, food intake (FI) and body weight, but the mechanisms are unclear. The purpose of this review was to examine research on the effects of nicotine on energy balance by exploring physiological mechanisms and hormone regulation related to FI, subjective appetite and energy expenditure (EE). We searched PubMed and MEDLINE, and included articles investigating the effects of nicotine on central appetite regulation, FI, leptin, peptide-YY (PYY), ghrelin, glucagon-like peptide-1 (GLP-1), adiponectin, cholecystokinin (CCK), orexin, and EE. A total of 65 studies were included in the qualitative synthesis and review. Our findings suggest that the decrease in appetite and FI may be attributed to nicotinic alterations of neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) but the effect of nicotine on FI remains unclear. Furthermore, nicotine increases resting EE (REE) and physical activity EE (PAEE) in both smokers and non-smokers; and these increases may be a result of the catecholaminergic effect of nicotine. Decreases in body weight and appetite experienced by nicotine users results from increased EE and changes in the central hypothalamic regulation of appetite. There is not enough evidence to implicate a relationship between peripheral hormones and changes in appetite or FI after nicotine use. Although nicotine increases REE and PAEE, the effect of nicotine on other components of EE warrants further research. We conclude that further research evaluating the effect of nicotine on appetite hormones, FI and EE in humans is warranted.

The daytime feeding frequency affects appetite-regulating hormones, amino acids, physical activity, and respiratory quotient, but not energy expenditure, in adult cats fed regimens for 21 days.

The effects of feeding frequency on postprandial response of circulating appetite-regulating hormones, insulin, glucose and amino acids, and on physical activity, energy expenditure, and respiratory quotient were studied in healthy adult cats. Two experiments were designed as a 2 x 3 replicated incomplete Latin square design. Eight cats, with an average body weight (BW) of 4.34 kg ± 0.04 and body condition score (BCS) of 5.4 ± 1.4 (9 point scale), were fed isocaloric amounts of a commercial adult maintenance canned cat food either once (0800 h) or four times daily (0800 h, 1130 h, 1500 h, 1830 h). Study 1 consisted of three 21-d periods. On day 14, two fasted and 11 postprandial blood samples were collected over 24 hours to measure plasma concentrations of ghrelin, GLP-1, GIP, leptin, PYY, insulin and amino acids, and whole blood glucose. Physical activity was monitored from day 15 to 21 of each period. In Study 2 indirect calorimetry was performed on the last day of each period. Body weight was measured weekly and feed intake recorded daily in both experiments. No effect of feeding regimen on BW was detected. Cats eating four times daily had lesser plasma concentrations of GIP and GLP-1 (P<0.05) and tended to have lesser plasma PYY concentrations (P<0.1). Plasma leptin and whole blood glucose concentrations did not differ between regimens (P>0.1). Cats fed once daily had a greater postprandial plasma amino acid response, and greater plasma ghrelin and insulin concentrations (P<0.05). Physical activity was greater in cats fed four times (P<0.05), though energy expenditure was similar between treatments at fasting and in postprandial phases. Finally, cats eating one meal had a lower fasting respiratory quotient (P<0.05). Overall, these data indicate that feeding once a day may be a beneficial feeding management strategy for indoor cats to promote satiation and lean body mass.

The drive to eat in homo sapiens: Energy expenditure drives energy intake.

The drive to eat is a component of appetite control, independent of the omnivorous habit of humans, and separate from food choice, satiety and food reward. The drive forms part of the tonic component of appetite and arises from biological needs; it is distinct from episodic aspects of appetite which are heavily influenced by culture and the environment (and which reflect the omnivorous habit). It is proposed that the tonic drive to eat reflects a need state generated by metabolic energy expenditure (EE) required to maintain the functioning and integrity of vital organs. Specifically, the tonic drive is quantitatively associated with fat-free mass (FFM) and resting metabolic rate (RMR). A rational proposition is that high metabolic rate organs (such as heart, liver, kidneys, brain) together with skeletal muscle generate a metabolic need which drives energy intake (EI). The basic phenomenon of a relationship between FFM, RMR and EI, first published in 2011, has been substantially replicated and there are at least 14 concordant published studies carried out in 9 different countries (and 4 continents) with various ethnic groups of lean and obese humans. These studies demonstrate that FFM and RMR represent major determinants of the drive to eat, and this is rational from an evolutionary perspective. The EE of bodily movements through skeletal muscle activity (namely physical activity and exercise) represents another driver which is clearly but more weakly associated with an increase in EI. This account of appetite control, developed within an energy balance framework, is consistent with the apparent inexorable escalation of fatness in individual humans, and for the progressive increase in the prevalence of obesity which, among other factors, reflects the difficulty of managing the biological drive to eat.

Compliance to oral nutritional supplementation decreases the risk of hospitalisation in malnourished older adults without extra health care cost: Prospective observational cohort study.

BACKGROUND & AIMS: Malnutrition affects 5-10% of elderly people living in the community. A few studies suggest that nutritional intervention may reduce health care costs. The present study included malnourished elderly patients living at home. It aimed to compare health care costs between patients that were prescribed ONS by their general practitioner and those who were not, and to assess the effect of ONS prescription on the risk of hospitalisation. METHODS: This prospective multicentre observational study included malnourished patients ≥70 years old who lived at home. Patients were defined as malnourished if they presented with one or more of the following criteria: weight loss ≥5% in 1 month, weight loss ≥10% in 6 months, BMI <21 kg/m2, albuminemia <35 g/L or Short-Form MNA ≤ 7. Their general practitioners prescribed an ONS, or not, according to their usual practice. Health care costs were recorded during a 6-month period. Other collected data were diseases, disability, self-perception of current health status, quality of life (QoL), nutritional status, appetite and compliance to ONS. A propensity score method was used to compare costs and risk of hospitalisation to adjust for potential confounding factors and control for selection bias. RESULTS: We analysed 191 patients. At baseline, the 133 patients (70%) who were prescribed ONS were more disabled (p < 0.001) and had poorer perception of their health (p = 0.02), lower QoL (p = 0.04) and lower appetite (p < 0.001) than the 58 patients (30%) who were not prescribed ONS. At 6 months, appetite had improved more in the ONS prescription group (p = 0.001). Weight change was not different between groups. Patients prescribed ONS were more frequently hospitalised (OR 2.518, 95% CI: [1.088; 5.829] hosp; p = 0.03). Analyses of adjusted populations revealed no differences in health care costs between groups. In the ONS prescription group, we identified that health care costs were lower (p = 0.042) in patients with an energy intake from ONS ≥ 500 kcal/d (1389 ± 264 €) vs. < 500 kcal/d (3502 ± 839 €). The risk of hospitalisation was reduced 3 and 5 times when the intake from ONS was ≥30 g of protein/day or ≥500 kcal/d, respectively. CONCLUSIONS: ONS prescription in malnourished elderly patients generated no extra heath care cost. High energy and protein intake from ONS was associated with a reduced risk of hospitalisation and health care costs.

Racial Variations in Appetite-Related Hormones, Appetite, and Laboratory-Based Energy Intake from the E-MECHANIC Randomized Clinical Trial.

African Americans (AAs) have a higher obesity risk than Whites; however, it is unclear if appetite-related hormones and food intake are implicated. We examined differences in appetite-related hormones, appetite, and food intake between AAs (n = 53) and Whites (n = 111) with overweight or obesity. Participants were randomized into a control group or into supervised, controlled exercise groups at 8 kcal/kg of body weight/week (KKW) or 20 KKW. Participants consumed lunch and dinner at baseline and follow-up, with appetite and hormones measured before and after meals (except leptin). At baseline, AAs had lower peptide YY (PYY; p < 0.01) and a blunted elevation in PYY after lunch (p = 0.01), as well as lower ghrelin (p = 0.02) and higher leptin (p < 0.01) compared to Whites. Despite desire to eat being lower and satisfaction being higher in AAs relative to Whites (p ≤ 0.03), no racial differences in food intake were observed. Compared to Whites, leptin increased in the 8 KKW group in AAs (p = 0.01), yet no other race-by-group interactions were evident. Differences in appetite-related hormones between AAs and Whites exist; however, their influence on racial disparities in appetite, food intake, and obesity within this trial was limited.

Energy Expenditure, Carbohydrate Oxidation and Appetitive Responses to Sucrose or Sucralose in Humans: A Pilot Study.

BACKGROUND: In light of obesity, replacing sugar with non-nutritive sweeteners is commonly used to reduce sugar content of food products. This study aimed to compare human energy expenditure (EE), carbohydrate oxidation and food intake after the ingestion of test foods sweetened with sucrose or a non-nutritive sweetener. METHODS: This was an acute crossover feeding study that entailed consumption of three test foods: jelly sweetened with 50 g sucrose (SUCROSE), with 120 mg of sucralose only (NNS), or 120 mg sucralose but matched in carbohydrate with 50 g maltodextrin (MALT). On test days, participants arrived at the research facility after an overnight fast. Resting energy expenditure (indirect calorimeter) was measured for 30 min followed by jelly consumption. Participants' EE and substrate oxidation were measured for 90 min subsequently. After EE assessment, participants completed a meal challenge before leaving the research facility, and recorded food intake for the remaining day. Subjective appetite ratings were assessed before and after test foods and meal challenge. RESULTS: Eleven participants completed the study. EE was higher in SUCROSE and MALT than NNS, but not statistically significant. Carbohydrate oxidation was SUCROSE > MALT > NNS (p < 0.001). Earlier and bigger rise in carbohydrate oxidation was observed in SUCROSE than MALT, although both were carbohydrate-matched. NNS did not promote energy expenditure, carbohydrate oxidation or stimulate appetite. CONCLUSIONS: Foods sweetened with sucrose or non-nutritive sweeteners but matched in carbohydrate content have different effects on human EE and carbohydrate oxidation. Sucralose alone did not affect EE, but lower energy in the test food from sugar replacement was eventually fully compensated. Findings from this pilot study should be verified with bigger clinical studies in the future to establish clinical relevance.

Appetite-Related Eating Behaviours: An Overview of Assessment Methods, Determinants and Effects on Children's Weight.

Identifying the underlying child-eating behaviours that contribute to weight differences across growth has been a constant challenge. This report reviews the various literature approaches for assessing appetite regulation. In doing so, it attempts to understand how appetite control develops and determines the eating habits in early childhood, and its effects on children's weight status. The interaction between homeostatic and hedonic mechanisms largely explains the appetite regulation process. Homeostatic mechanisms are mediated by the biological need to maintain the body's energy reserves, increasing the motivation to eat. On the contrary, the hedonic mechanisms are mediated by food reward, increasing the craving for high-palatable foods and triggering the release of dopamine and serotonin. There are many biological methods (plasma measurements of hormones, like leptin, ghrelin and insulin) and behavioural evaluation methods of appetite. The Children's Eating Behaviour Questionnaire is most commonly used, due to its adequate psychometric properties tested in several population settings. The development of eating behaviours begins in utero, and several determinants may contribute to a decrease in the ability to self-regulate dietary intake. Examples include genetic predisposition, the first taste experiences and the family environment, a key determinant in this process. Several eating behaviours contribute most to childhood obesity. Among them, are the external eating (eating by external stimuli, such as the mere presence of the food or its smell), food restriction (which may potentiate the uninhibited increased intake of the restricted foods) and emotional eating (intake due to emotional variations, especially negative feelings). These eating behaviours have been linked to childhood obesity.

What Is the Evidence for "Food Addiction?" A Systematic Review.

The diagnostic construct of "food addiction" is a highly controversial subject. The current systematic review is the first to evaluate empirical studies examining the construct of "food addiction" in humans and animals. Studies were included if they were quantitative, peer-reviewed, and in the English language. The 52 identified studies (35 articles) were qualitatively assessed to determine the extent to which their findings indicated the following addiction characteristics in relation to food: brain reward dysfunction, preoccupation, risky use, impaired control, tolerance/withdrawal, social impairment, chronicity, and relapse. Each pre-defined criterion was supported by at least one study. Brain reward dysfunction and impaired control were supported by the largest number of studies (n = 21 and n = 12, respectively); whereas risky use was supported by the fewest (n = 1). Overall, findings support food addiction as a unique construct consistent with criteria for other substance use disorder diagnoses. The evidence further suggests that certain foods, particularly processed foods with added sweeteners and fats, demonstrate the greatest addictive potential. Though both behavioral and substance-related factors are implicated in the addictive process, symptoms appear to better fit criteria for substance use disorder than behavioral addiction. Future research should explore social/role impairment, preoccupation, and risky use associated with food addiction and evaluate potential interventions for prevention and treatment.

Effect of physical exercise on spontaneous physical activity energy expenditure and energy intake in overweight adults (the EFECT study): a study protocol for a randomized controlled trial.

BACKGROUND: Physical exercise interventions have been extensively advocated for the treatment of obesity; however, clinical trials evaluating the effectiveness of exercise interventions on weight control show controversial results. Compensatory mechanisms through a decrease in energy expenditure and/or an increase in caloric consumption is a possible explanation. Several physiological mechanisms involved in the energy balance could explain compensatory mechanisms, but the influences of physical exercise on these adjustments are still unclear. Therefore, the present trial aims to evaluate the effects of exercise on non-exercise physical activity energy expenditure, energy intake and appetite sensations among active overweight/obese adults, as well as, to investigate hormonal changes associated with physical exercise. METHODS: This study is a randomized controlled trial with parallel, three-group experimental arms. Eighty-one overweight/obese adults will be randomly allocated (1:1:1 ratio) to a vigorous exercise group, moderate exercise group or control group. The trial will be conducted at a military institution and the intervention groups will be submitted to exercise sessions in the evening, three times a week for 65 min, during a 2-week period. The primary outcome will be total spontaneous physical activity energy expenditure during a 2-week period. Secondary outcomes will be caloric intake, appetite sensations and laboratorial biomarkers. Intention-to-treat analysis will be performed using linear mixed-effects models to evaluate the effect of treatment-by-time interaction on primary and secondary outcomes. Data analysis will be performed using SAS 9.3 and statistical significance will be set at p < 0.05. DISCUSSION: The results of the present study will help to understand the effect of physical exercise training on subsequent non-exercise physical activity, appetite and energy intake as well as understand the physiological mechanisms underlying a possible compensatory phenomenon, supporting the development of more effective interventions for prevention and treatment of obesity. TRIAL REGISTRATION: Physical Exercise and Energy Balance trial registry, trial registration number: NCT 03138187 . Registered on 30 April 2017.

What makes people leave their food? The interaction of personal and situational factors leading to plate leftovers in canteens.

In order to provide a basis for the reduction of food losses, our study analyzes individual food choice, eating and leftover behavior in a university canteen by consideration of personal, social and environmental determinants. Based on an extended literature review, a structural equation model is derived and empirically tested for a sample of 343 students. The empirical estimates support the derived model with a good overall model fit and sufficient R2 values for dependent variables. Hence, our results provide evidence for a general significant impact of behavioral intention and related personal and social determinants as well as for the relevance of environmental/situational determinants such as portion sizes and palatability of food for plate leftovers. Moreover, we find that environmental and personal determinants are interrelated and that the impact of different determinants is relative to perceived time constraints during a visit of the university canteen. Accordingly, we conclude that simple measures to decrease avoidable food waste may take effects via complex and interrelated behavioral structures and that future research should focus on these effects to understand and change food leftover behavior.

Appetite self-regulation: Environmental and policy influences on eating behaviors.

OBJECTIVE: Appetite regulation is influenced by the environment, and the environment is shaped by food-related policies. This review summarizes the environment and policy research portion of an NIH Workshop (Bethesda, MD, 2015) titled "Self-Regulation of Appetite-It's Complicated." METHODS: In this paper, we begin by making the case for why policy is an important tool in efforts to improve nutrition, and we introduce an ecological framework that illustrates the multiple layers that influence what people eat. We describe the state of the science on how policies influence behavior in several key areas: the federal food programs, schools, child care, food and beverage pricing, marketing to youth, behavioral economics, and changing defaults. Next, we propose novel approaches for multidisciplinary prevention and intervention strategies to promote breastfeeding, and examine interactions between psychology and the environment. RESULTS: Policy and environmental change are the most distal influences on individual-level appetite regulation, yet these strategies can reach many people at once by changing the environment in which food choices are made. We note the need for more research to understand compensatory behavior, reactance, and how to effectively change social norms. CONCLUSIONS: To move forward, we need a more sophisticated understanding of how individual psychological and biological factors interact with the environment and policy influences.

From the past to future: from energy expenditure to energy intake to energy expenditure.

Although most recent research on energy balance focusses on energy intake (EI) there is still need to think about both sides of the energy balance. Current research on energy expenditure (EE) relates to metabolic adaptation to negative energy balance, mitochondrial metabolism associated with aging, obesity and type 2 diabetes mellitus, the role of EE in hunger and appetite control, non-shivering thermogenesis and brown adipose tissue activity, cellular bioenergetics as a target of obesity treatment and the evolutionary and ecological determinants of EE in humans and other primates. As far as regulation of energy balance is concerned there is recent evidence that EE rather than body weight is under tight control. Biologically, EE is maintained within a narrow physiological range. An EE-set point has been proposed as the width between the upper and lower boundaries of the individual EE range. Regulation of EE may fail in very obese patients with an EI above their upper boundary and after drastic weight loss when patients may go far below their lower EE boundary and thus are loosing control. In population studies, fat-free mass (FFM) and its composition (that is, the proportion of high to low metabolic rate organs) are major determinants of EE. It is tempting to speculate that tight biologic control of EE is related to brain energy need, which is preserved at the cost of peripheral metabolism. There is a moderate heritability of EE, which is independent of the heritability of FFM. In future, metabolic phenotyping should focus on the EE-FFM relationship rather than on EE-values alone.

A minireview of effects of green tea on energy expenditure.

In recent years, individuals have begun to tend more frequently to some natural and herbal products to be used alone or as a combination with diet and exercise for ensuring the weight loss. Green tea is the leading one of these products. In some studies, it is reported that the green tea causes an increase in thermogenesis and substrate with fat oxidation by affecting on the sympathetic nervous system. It is reported that green tea has two main components that are associated with energy expenditure. One of them is caffeine and the other is catechin content. Each of these two components has an impact on energy mechanism separately. In this minireview article, mechanisms of action and effects of caffeine and catechin, which are found in green tea composition, on energy expenditure are assessed.

Mouth rinsing with a sweet solution increases energy expenditure and decreases appetite during 60 min of self-regulated walking exercise.

Carbohydrate mouth rinsing can improve endurance exercise performance and is most ergogenic when exercise is completed in the fasted state. This strategy may also be beneficial to increase exercise capacity and the energy deficit achieved during moderate-intensity exercise relevant to weight control when performed after an overnight fast. Eighteen healthy men (mean (SD); age, 23 (4) years; body mass index, 23.1 (2.4) kg·m-2) completed a familiarisation trial and 3 experimental trials. After an overnight fast, participants performed 60 min of treadmill walking at a speed that equated to a rating of perceived exertion of 13 ("fairly hard"). Participants manually adjusted the treadmill speed to maintain this exertion. Mouth rinses for the experimental trials contained either a 6.4% maltodextrin solution with sweetener (CHO), a taste-matched placebo (PLA), or water (WAT). Appetite ratings were collected using visual analogue scales and exercise energy expenditure and substrate oxidation were calculated from online gas analysis. Increased walking distance during CHO and PLA induced greater energy expenditure compared with WAT (mean difference (90% confidence interval); 79 (60) kJ, P = 0.035, d = 0.24; and 90 (63) kJ, P = 0.024, d = 0.27, respectively). Appetite area under the curve was lower in CHO and PLA than WAT (8 (6) mm, P = 0.042, d = 0.43; and 6 (8) mm, P = 0.201, d = 0.32, respectively). Carbohydrate oxidation was higher in CHO than PLA and WAT (7.3 (6.7) g, P = 0.078, d = 0.47; and 10.1 (6.5) g, P = 0.015, d = 0.81, respectively). This study provides novel evidence that mouth rinsing with a sweetened solution may promote a greater energy deficit during moderate-exertion walking exercise by increasing energy expenditure and decreasing appetite. A placebo effect may have contributed to these benefits.

Effects of a 12-week aerobic exercise intervention on eating behaviour, food cravings, and 7-day energy intake and energy expenditure in inactive men.

This study examined effects of 12 weeks of moderate-intensity aerobic exercise on eating behaviour, food cravings, and weekly energy intake and expenditure in inactive men. Eleven healthy men (mean ± SD: age, 26 ± 5 years; body mass index, 24.6 ± 3.8 kg·m-2; maximum oxygen uptake, 43.1 ± 7.4 mL·kg-1·min-1) completed the 12-week supervised exercise programme. Body composition, health markers (e.g., blood pressure), eating behaviour, food cravings, and weekly energy intake and expenditure were assessed before and after the exercise intervention. There were no intervention effects on weekly free-living energy intake (p = 0.326, d = -0.12) and expenditure (p = 0.799, d = 0.04) or uncontrolled eating and emotional eating scores (p > 0.05). However, there was a trend with a medium effect size (p = 0.058, d = 0.68) for cognitive restraint to be greater after the exercise intervention. Total food cravings (p = 0.009, d = -1.19) and specific cravings of high-fat foods (p = 0.023, d = -0.90), fast-food fats (p = 0.009, d = -0.71), and carbohydrates/starches (p = 0.009, d = -0.56) decreased from baseline to 12 weeks. Moreover, there was a trend with a large effect size for cravings of sweets (p = 0.052, d = -0.86) to be lower after the exercise intervention. In summary, 12 weeks of moderate-intensity aerobic exercise reduced food cravings and increased cognitive restraint, but these changes were not accompanied by changes in other eating behaviours or weekly energy intake and expenditure. The results indicate the importance of exercising for health improvements even when reductions in body mass are modest.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity.

OBJECTIVE: The brain's reward system influences ingestive behavior and subsequently obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. This study sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. METHODS: A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n = 16) and men (n = 12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the two testing days. RESULTS: Mean fasting-state brain responses on day 2 were reduced compared with day 1 in the left insula and right amygdala, but mean day 1 and day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. CONCLUSIONS: fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies.