The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity.

AIM: To investigate the effects of once-weekly subcutaneous (s.c.) semaglutide 2.4 mg on gastric emptying, appetite, and energy intake in adults with obesity. MATERIALS AND METHODS: A double-blind, parallel-group trial was conducted in 72 adults with obesity, randomized to once-weekly s.c. semaglutide (dose-escalated to 2.4 mg) or placebo for 20 weeks. Gastric emptying was assessed using paracetamol absorption following a standardized breakfast. Participant-reported appetite ratings and Control of Eating Questionnaire (CoEQ) responses were assessed, and energy intake was measured during ad libitum lunch. RESULTS: The area under the concentration-time curve (AUC) for paracetamol 0 to 5 hours after a standardized meal (AUC0-5h,para ; primary endpoint) was increased by 8% (P = 0.005) with semaglutide 2.4 mg versus placebo at week 20 (non-significant when corrected for week 20 body weight; P = 0.12). No effect was seen on AUC0-1h,para , maximum observed paracetamol concentration, or time to maximum observed paracetamol concentration. Ad libitum energy intake was 35% lower with semaglutide versus placebo (1736 versus 2676 kJ; estimated treatment difference -940 kJ; P <0.0001). Semaglutide reduced hunger and prospective food consumption, and increased fullness and satiety when compared with placebo (all P <0.02). The CoEQ indicated better control of eating and fewer/weaker food cravings with semaglutide versus placebo (P <0.05). Body weight was reduced by 9.9% with semaglutide and 0.4% with placebo. Safety was consistent with the known profile of semaglutide. CONCLUSIONS: In adults with obesity, once-weekly s.c. semaglutide 2.4 mg suppressed appetite, improved control of eating, and reduced food cravings, ad libitum energy intake and body weight versus placebo. There was no evidence of delayed gastric emptying at week 20, assessed indirectly via paracetamol absorption.

Enhancing hepatic mitochondrial fatty acid oxidation stimulates eating in food-deprived mice.

Hepatic fatty acid oxidation (FAO) has long been implicated in the control of eating. Nevertheless, direct evidence for a causal relationship between changes in hepatic FAO and changes in food intake is still missing. Here we tested whether increasing hepatic FAO via adenovirus-mediated expression of a mutated form of the key regulatory enzyme of mitochondrial FAO carnitine palmitoyltransferase 1A (CPT1mt), which is active but insensitive to inhibition by malonyl-CoA, affects eating and metabolism in mice. CPT1mt expression increased hepatocellular CPT1 protein levels. This resulted in an increase in circulating ketone body levels in fasted CPT1mt-expressing mice, suggesting an increase in hepatic FAO. These mice did not show any significant changes in cumulative food intake, energy expenditure, or respiratory quotient after 4-h food deprivation. After 24-h food deprivation, however, the CPT1mt-expressing mice displayed increased food intake. Thus expression of CPT1mt in the liver increases hepatic FAO capacity, but does not inhibit eating. Rather, it may even stimulate eating after prolonged food deprivation. These data do not support the hypothesis that an increase in hepatic FAO decreases food intake.

Control of Eating Attributes and Weight Loss Outcomes over One Year After Sleeve Gastrectomy.

PURPOSE: Sleeve gastrectomy (SG) is a commonly performed metabolic-bariatric surgery, but its effectiveness is variable and difficult to predict. Our study aimed to compare control of eating (CoE) attributes pre- and post-SG depending on the achievement of optimal weight loss target at 1 year post-SG. MATERIALS AND METHODS: A prospective longitudinal cohort study using the CoE Questionnaire, pre-SG, and postoperatively at 3, 6, and 12 months was conducted. Total weight loss (TWL) ≥ 25% at 12 months post-SG was set as an optimal weight loss target. RESULTS: Forty-one patients (80.5% females, mean age 41.7 ± 10.6) were included. Sex, age, baseline weight, BMI, and smoking status were all comparable. At 3 months post-SG, "difficulty to control eating" score became significantly different between ≥ 25%TWL and < 25%TWL groups (7 [0-50] vs. 17 [5-63], p = 0.042). At 6 months, it was followed by "feeling of fullness," "frequency of food cravings," and "difficulty to resist cravings" demonstrating significant differences between ≥ 25%TWL and < 25%TWL groups. At 12 months, significant differences between groups were observed in "feeling hungry," "difficulty to resist cravings," "eating in response to cravings," and difficulty to control eating scores. CONCLUSION: Individuals with obesity who achieved a target of ≥ 25%TWL at 1 year post-SG have an early improvement in overall eating control at 3 months that steadily persists at 6 and 12 months. Improvements in other aspects tend to follow later, at 6 and 12 months. These findings may assist in identifying individuals with inadequate response to help attain optimal weight loss targets and developing a prognostic model to identify predictors of successful weight loss.

Stronger control of eating 3 months after sleeve gastrectomy predicts successful weight loss outcomes at one year.

Background: Weight loss response to sleeve gastrectomy (SG) is variable and predicting the effectiveness of surgery is challenging and elusive. The aim of our study was to assess and quantify the association between eating control and weight loss outcomes and identify the control of eating (CoE) attributes during the early postoperative period that might predict good vs. poor response to SG at one year. Methods: A prospective longitudinal cohort study using the Control of Eating Questionnaire (CoEQ) was designed as a series before and at 3-, 6-, and 12-months post-SG. Primary outcomes were changes in CoE attributes and percent of total weight loss (%TWL) 12-months post-surgery. Subjects were categorized based on %TWL as good (GR, ≥25 %) or poor responders (PR, <25 %). A receiver operating characteristic and logistic regression analyses were performed. Results: We included 41 participants (80.5% females, 51.2% Hispanic, mean age 41.7±10.6, median baseline body mass index (BMI) 43.6 kg/m2 [range 35.2-66.3]) who completed the CoEQ at all four timepoints. The "Difficulty to control eating" score at 3 months revealed the highest area under the curve (AUC) (AUC 0.711; 95%CI 0.524-0.898; p=0.032). In a trade-off between a high Youden index and high sensitivity, the "Difficulty to control eating" score of 7 at 3 months was identified as the optimal cut-off for distinguishing between GRs and PRs. Score ≤7 at 3 months was strongly independently associated with a successful weight loss target of 25%TWL at one-year post-SG (Relative Risk 4.43; 95%CI 1.06-18.54; p=0.042). Conclusion: "Difficulty to control eating" score at 3 months post-SG is an independent early predictor of optimal response (achieving a successful TWL target of ≥25 % at one-year post-SG). Our results support the utility of this easy-to-administer validated tool for predicting the effectiveness of SG and may assist in identifying individuals with suboptimal response early and helping them with interventions to attain optimal weight loss targets.

Eating behavior as a new frontier in memory research.

The study of memory is commonly associated with neuroscience, aging, education, and eyewitness testimony. Here we discuss how eating behavior is also heavily intertwined-and yet considerably understudied in its relation to memory processes. Both are influenced by similar neuroendocrine signals (e.g., leptin and ghrelin) and are dependent on hippocampal functions. While learning processes have long been implicated in influencing eating behavior, recent research has shown how memory of recent eating modulates future consumption. In humans, obesity is associated with impaired memory performance, and in rodents, dietary-induced obesity causes rapid decrements to memory. Lesions to the hippocampus disrupt memory but also induce obesity, highlighting a cyclic relationship between obesity and memory impairment. Enhancing memory of eating has been shown to reduce future eating and yet, little is known about what influences memory of eating or how memory of eating differs from memory for other behaviors. We discuss recent advancements in these areas and highlight fruitful research pursuits afforded by combining the study of memory with the study of eating behavior.

A physiological perspective on the neuroscience of eating.

I present the thesis that 'being physiological,' i.e., analyzing eating under conditions that do not perturb, or minimally perturb, the organism's endogenous processes, should be a central goal of the neuroscience of eating. I describe my understanding of 'being physiological' based on [i] the central neural-network heuristic of CNS function that traces back to Cajal and Sherrington, [ii] research on one of the simpler problems in the neuroscience of eating, identification of endocrine signals that control eating. In this context I consider natural meals, physiological doses and ranges, and antagonist studies. Several examples involve CCK. Next I describe my view of the cutting edge in the molecular neuroscience of eating as it has evolved from the discovery of leptin signaling through the application of optogenetic and pharmacogenetic methods. Finally I describe some novel approaches that may advance the neuroscience of eating in the foreseeable future. I conclude that [i] the neuroscience of eating may soon be able to discern 'physiological' function in the operation of CNS networks mediating eating, [ii] the neuroscience of eating should capitalize on methods developed in other areas of neuroscience, e.g., improved methods to record and manipulate CNS function in behaving animals, identification of canonical regional circuits, use of population electrophysiology, etc., and [iii] subjective aspects of eating are crucial aspects of eating science, but remain beyond mechanistic understanding.