Time of day differences in appetite and gut hormone responses to meal and stress challenges in adults with normal-weight and obesity.

BACKGROUND: Lifestyle factors like time of eating and stress exposure may impact physiology to promote excess weight gain. To understand behavioral and physiological mechanisms underlying these potential effects, we compared appetite and gut hormone responses to a series of meal and stress challenges beginning in the morning and the afternoon, in adults with normal-weight and obesity. METHOD: Thirty-two adults (16 with normal-weight, 16 with obesity) underwent the same test protocol on different days, each following an 8 h fast. On one day the protocol began in the morning (AM condition); on the other day it began in the late afternoon (PM condition). On each day they first received a standardized liquid meal (9:00am/4:00pm), then a stress test (Socially-Evaluated Cold Pressor Test, 11:10am/6:10pm), then an ad libitum buffet meal (11:40am/6:40pm). Appetite and stress ratings were obtained, and blood was drawn for measures of ghrelin, PYY, GLP-1, insulin, glucose, cortisol and leptin. Acetaminophen was administered as a tracer to assess gastric emptying of the liquid meal. RESULTS: Across all three challenges, AUC cortisol was lower in the PM vs. AM condition (all p<.001), and AUC insulin and leptin were higher in the obesity vs. normal-weight group (all p<.001). For the standardized liquid meal only, AUC hunger, desire to eat and ghrelin were greater in the PM vs. AM condition (all p<0.05), and AUC ghrelin was lower in the obesity vs. normal-weight group, even when controlling for baseline values (p<0.05). AUC glucose was higher in the evening for the normal-weight group only (condition x group interaction p<0.05). Post-liquid meal gastric emptying as indexed by AUC acetaminophen was slower in the PM vs. AM (p<.01). For the stress test, AUC cortisol was lower in the PM than the AM condition even when controlling for baseline values (p<.05). AUC leptin was lower in the evening in the obesity group only (condition x group interaction p<0.01). PYY showed an acute decrease post-stressor in the normal-weight but not the obesity group (p<.05). Post-stress ad libitum buffet meal intake was similar in the evening and morning conditions, and higher in the obesity group (p<0.05). Only among the obesity group in the evening condition, higher stressor-associated stress and cortisol were associated with greater meal-associated appetite (p<0.05). CONCLUSIONS: Normal-weight individuals and those with obesity may be at risk of evening overeating as a result of differential appetite and gut hormone responses following meal intake and stress exposure.

Meal-Related Acyl and Des-Acyl Ghrelin and Other Appetite-Related Hormones in People with Obesity and Binge Eating.

OBJECTIVE: Potential mechanisms of abnormal food intake, such as dysregulation of meal-related appetite hormones, including acyl ghrelin (AG) and des-acyl ghrelin (DAG), were investigated among men and women with obesity, with and without binge eating (BE). METHODS: Participants (n = 42: 19 female, 23 male) were assigned to a liquid meal and water condition in counterbalanced order, and blood samples for measuring hormones were obtained before and after these conditions. RESULTS: Participants with BE had significantly lower fasting and postingestive AG concentrations than participants without BE in both conditions. During the meal condition, postprandial decreases in AG concentrations were significantly smaller for the BE group than for the non-BE group. There were no significant differences in DAG by BE group. Leptin increased significantly less after meals for those with BE compared with those without BE. There were no differences in other hormones by BE group. Fasting and postmeal hunger ratings were significantly higher for those with BE than for those without BE. CONCLUSIONS: In individuals with BE, lower fasting AG may be due to downregulation by habitual overeating, and a smaller postmeal decline in AG may contribute to overeating. Lower postmeal leptin concentrations may also contribute to overeating.

Plasma cortisol levels in response to a cold pressor test did not predict appetite or ad libitum test meal intake in obese women.

Heightened cortisol response to stress due to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis may stimulate appetite and food intake. In this study, we assessed cortisol responsivity to a cold pressor test (CPT) as well as appetite ratings and subsequent test meal intake (TMI) in obese women. Following an overnight fast on two counterbalanced days, 20 obese women immersed their non-dominant hand for 2min in ice water (CPT) or warm water (WW) as a control. Plasma cortisol (ng/ml), heart rate, and blood pressure, as well as ratings of stress, pain, and appetite, were serially acquired. An ad libitum liquid meal was offered at 45min and intake measured covertly. Fasting cortisol was higher at 15min (mean peak cortisol) following the CPT compared to WW. Higher stress was reported at 2 and 15min for the CPT compared to WW. Pain, an indirect marker of the acute stress, systolic and diastolic blood pressure increased following the CPT at 2min compared to WW. Hunger decreased after the CPT at 2 and 15min, and desire to eat ratings were lower following CPT compared to WW. Subjects did not have greater test meal intake (TMI) following CPT compared to WW. There was also no significant relationship between cortisol levels following stress and TMI, indicating that cortisol did not predict subsequent intake in obese women.

Partitioning of the plasma membrane Ca2+-ATPase into lipid rafts in primary neurons: effects of cholesterol depletion.

Spatial and temporal alterations in intracellular calcium [Ca(2+)](i) play a pivotal role in a wide array of neuronal functions. Disruption in Ca(2+) homeostasis has been implicated in the decline in neuronal function in brain aging and in neurodegenerative disorders. The plasma membrane Ca(2+)-ATPase (PMCA) is a high affinity Ca(2+) transporter that plays a crucial role in the termination of [Ca(2+)](i) signals and in the maintenance of low [Ca(2+)](i) essential for signaling. Recent evidence indicates that PMCA is uniquely sensitive to its lipid environment and is stimulated by lipids with ordered acyl chains. Here we show that both PMCA and its activator calmodulin (CaM) are partitioned into liquid-ordered, cholesterol-rich plasma membrane microdomains or 'lipid rafts' in primary cultured neurons. Association of PMCA with rafts was demonstrated in preparations isolated by sucrose density gradient centrifugation and in intact neurons by confocal microscopy. Total raft-associated PMCA activity was much higher than the PMCA activity excluded from these microdomains. Depletion of cellular cholesterol dramatically inhibited the activity of the raft-associated PMCA with no effect on the activity of the non-raft pool. We propose that association of PMCA with rafts represents a novel mechanism for its regulation and, consequently, of Ca(2+) signaling in the central nervous system.