Biology subjects

Hall, K. D.

Publications and source records attributed to Hall, K. D..

8 recordsLinked to original sources

bioRxiv2026

When does post-ingestive dopamine signaling occur in humans?

The post-ingestive dopamine response is an integral determinant of subsequent eating behavior in animals yet measurement of the post-ingestive response to nutrients in humans has been elusive when assessed in the early post-ingestive period (30 minutes postprandially). We conducted secondary analysis comparing dopamine D2 receptor binding potential (D2BP) measured using [18F]fallypride positron emission tomography in two inpatient controlled feeding cohorts consuming standardized diet (50% carbohydrate; 35% fat; 15% protein) with similar characteristics and procedures but differing in time since last meal: confirmed overnight fast (n=57; 66.7% female; BMI 29.6{+/-}7.6 kg/m2; 31.9{+/-}7.2 years old) and 2-hours after a standardized meal reflecting 20% of energy requirements (n=43; 48.8% female; BMI 28.8{+/-}7.8 kg/m2, 31.3{+/-}7.7 years old). Compared to the fasted cohort, the 2-hour postprandial cohort exhibited significantly reduced whole striatal D2BP (p<0.0001) as well as in clusters in insular cortex, prefrontal cortex which remained after adjustment for age, sex, and insulin sensitivity. Voxelwise comparisons of the relationship between D2BP and BMI in the fasted and fed cohorts reveals clusters within dorsolateral and ventral striatum where dopamine level is dependent on postprandial state and adiposity. Given the similarities between protocol procedures and participant characteristics, our results suggest that the post-ingestive dopamine response to nutrients may be prominent in the extended post-ingestive period and warrant investigation within-subject.

neuroscience↗

bioRxiv2026

Why Do Patients with Type 2 Diabetes Lose Less Weight on GLP-1s? A Mathematical Modeling Analysis

Objective: To investigate the extent to which attenuation of weight loss observed in patients with Type 2 Diabetes (T2D) treated with semaglutide can be quantitatively explained by changes in energy expenditure and urinary glucose excretion (UGE) that occur with improved glycemic control. Methods: A previously validated mathematical model of human energy balance dynamics was modified to simulate patients with T2D by including the effects of hyperglycemia on energy expenditure as well as UGE calculated based on estimated glomerular filtration rate (eGFR), renal threshold (RT) for glucose reabsorption, and estimated plasma glucose derived from measured glycated hemoglobin (HbA1c). Treatment with sodium glucose co-transporter 2 inhibitors (SGLT2i) was simulated by lowering RT. Results: Attenuated semaglutide induced weight losses in T2D patients without background SGLT2i therapy were partially explained by changes in UGE and energy expenditure. Patients with T2D on stable background SGLT2i therapy were predicted to have the greatest attenuation of weight loss. Conclusions: Changes in energy expenditure and UGE associated with glycemic improvements can substantially offset negative energy balance in patients with T2D treated with semaglutide, especially in patients on stable background SGLT2i therapy.

physiology↗

bioRxiv2023

Physiology of the Weight Loss Plateau after Calorie Restriction, GLP-1 Receptor Agonism, and Bariatric Surgery

ObjectiveTo investigate why different weight loss interventions result in varying durations of weight loss prior to approaching plateaus. MethodsA validated mathematical model of energy balance and body composition dynamics was used to simulate mean weight loss trajectories in response to intensive calorie restriction, semaglutide 2.4 mg, tirzepatide 10 mg, and Roux en-Y gastric bypass (RYGB) surgery interventions. Each intervention was simulated by varying two model parameters affecting energy intake to fit the observed mean weight loss data. One parameter represented the persistent magnitude of the intervention to shift the system from baseline equilibrium and the other parameter represented the strength of the feedback control circuit relating weight loss to increased appetite. ResultsRYGB surgery resulted in a persistent intervention magnitude more than 4-fold greater than calorie restriction and about double that of tirzepatide and semaglutide. All interventions except calorie restriction substantially weakened the appetite feedback control circuit resulting in an extended period of weight loss prior to the plateau. ConclusionsThese preliminary mathematical modeling results suggest that both GLP-1 receptor agonism and RYGB surgery interventions act to weaken the appetite feedback control circuit regulating body weight and induce greater persistent effects to shift the body weight equilibrium as compared to intensive calorie restriction.

physiology↗

bioRxiv2022

A data-driven approach to quantifying meal characteristics influencing energy intake

We used a data-driven approach to determine the influence of energy density, hyper-palatability, protein content, and eating rate on ad libitum non-beverage energy intake during 2733 meals consumed by 35 inpatient adults who participated in two 28-day feeding studies. All four meal characteristics significantly contributed to energy intake, but their relative importance varied by the prevailing dietary pattern according to macronutrient composition and degree of processing.

physiology↗

bioRxiv2022

Restriction of dietary fat, but not carbohydrate, alters brain reward circuitry in adults with obesity

Weight loss diets often target restriction of dietary fat or carbohydrate, macronutrients that are sensed via distinct gut-brain pathways and differentially affect peripheral hormones and metabolism. However, the effects of such diet changes on human brain are unclear. We investigated whether selective isocaloric reductions in dietary fat or carbohydrate altered dopamine D2/3 receptor binding potential (D2BP) and neural activity in brain reward regions in response to visual food cues in 17 inpatient adults with obesity as compared to a eucaloric baseline diet. On the fifth day of dietary fat restriction, but not carbohydrate restriction, both D2BP and neural activity to food cues were decreased in brain reward regions. After the reduced fat diet, ad libitum intake shifted towards foods high in both fat and carbohydrates. These results suggest that dietary fat restriction increases tonic dopamine in brain reward regions and affects food choice in ways that may hamper diet adherence.

neuroscience↗

bioRxiv2018

No Significant Effect of Dietary Carbohydrate versus Fat on the Reduction in Total Energy Expenditure During Maintenance of Lost Weight: A Secondary Analysis

Key messagesO_LIThe latest battle in the perpetual diet wars claimed that low carbohydrate diets offer a metabolic advantage to burn more calories and thereby help patients maintain lost weight. C_LIO_LIHowever, analyzing the data according to the original pre-registered statistical plan resulted in no statistically significant effects of diet composition on energy expenditure. C_LIO_LIThe large reported diet effect on expenditure calculated using the revised analysis plan depended on data from subjects with excessive amounts of unaccounted energy. Adjusting the data to be commensurate with energy conservation resulted in a diet effect that was less than half the value reported in the BMJ paper. C_LIO_LIThe measured daily average CO2 production rates were not significantly different between the diets and the reported expenditure differences were due to inaccurate calculations based on false assumptions about diet adherence. C_LI

physiology↗

bioRxiv2018

Objective versus Self-Reported Energy Intake Changes During Low-Carbohydrate and Low-Fat Diets

ObjectiveTo examine objective versus self-reported energy intake changes ({Delta}EI) during a 12-month diet intervention.\n\nMethodsWe calculated {Delta}EI in subjects who participated in a 1-year randomized low-carbohydrate versus low-fat diet trial using repeated body weight measurements as inputs to an objective mathematical model ({Delta}EIModel) and compared these values with self-reported energy intake changes assessed by repeated 24-hr recalls ({Delta}EI24hrRecall).\n\nResults{Delta}EI24hrRecall indicated a relatively persistent state of calorie restriction [≥]500 kcal/d throughout the year with no significant differences between diets. {Delta}EIModel demonstrated large early decreases in calorie intake >800 kcal/d followed by an exponential return to approximately 100 kcal/d below baseline at the end of the year. The low-carbohydrate diet resulted in {Delta}EIModel that was 162{+/-}53 kcal/d lower than the low-fat diet over the first 3 months (p=0.002), but no significant diet differences were found at later times. Weight loss at 12 months was significantly related to {Delta}EIModel at all time intervals for both diets (p<0.0001).\n\nConclusionsSelf-reported measurements of {Delta}EI were inaccurate. Model-based calculations of {Delta}EI found that instructions to follow the low-carbohydrate diet resulted in greater calorie restriction than the low-fat diet in the early phases of the intervention, but these diet differences were not sustained.\n\nWhat is already known about this subject?O_LIDiet assessments that rely on self-report, such as 24hr dietary recall, are known to underestimate actual energy intake as measured by doubly labeled water. However, it is possible that repeated self-reported measurements could accurately detect changes in energy intake over time if the absolute bias of self-reported of measurements is approximately constant for each subject.\nC_LI\n\nWhat this study addsO_LIWe compared energy intake changes measured using repeated 24hr dietary recall measurements collected over the course of the 1-year Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial versus energy intake changes calculated using repeated body weight measurements as inputs to a validated mathematical model.\nC_LIO_LIWhereas self-reported measurements indicated a relatively persistent state of calorie restriction, objective model-based measurements demonstrated a large early calorie restriction followed by an exponential rise in energy intake towards the pre-intervention baseline.\nC_LIO_LIModel-based calculations, but not self-reported measurements, found that low-carbohydrate diets led to significantly greater early decreases in energy intake compared to low-fat diets, but long-term energy intake changes were not significantly different.\nC_LI

physiology↗

bioRxiv2018

Potential Bias of Doubly Labeled Water for Measuring Energy Expenditure Differences Between Diets Varying in Carbohydrate

BackgroundVery low-carbohydrate diets have been reported to substantially increase human energy expenditure as measured by doubly labeled water (DLW) but not by respiratory chambers. Do the DLW data reflect true physiological differences that are undetected by respiratory chambers? Alternatively, are the apparent DLW energy expenditure a consequence of failure to fully account for respiratory quotient (RQ) differences between diets?\n\nObjectiveTo examine energy expenditure differences between diets varying drastically in carbohydrate and to quantitatively compare DLW data with respiratory chamber and body composition measurements within an energy balance framework.\n\nDesignDLW measurements were obtained during the final two weeks of month-long baseline (BD; 50% carbohydrate, 35% fat, 15% protein) and isocaloric ketogenic diets (KD; 5% carbohydrate, 80% fat, 15% protein) in 17 men with BMI 25-35 kg/m2. Subjects resided 2d/week in respiratory chambers to measure energy expenditure (EEchamber). DLW expenditure was calculated using chamber-determined respiratory quotients (RQ) either unadjusted (EEDLW) or adjusted (EEDLW{Delta}RQ) for net energy imbalance using diet-specific coefficients. Accelerometers measured physical activity. Body composition changes were measured by dual-energy X-ray absorptiometry which were combined with energy intake measurements to calculate energy expenditure by balance (EEbal).\n\nResultsAfter transitioning from BD to KD, neither EEchamber nor EEbal were significantly changed ({triangleup}EEchamber=24{+/-}30 kcal/d; p=0.43 and {triangleup}EEbal=-141{+/-}118 kcal/d; p=0.25). Similarly, physical activity (-5.1{+/-}4.8%; p=0.3) and exercise efficiency (-1.6{+/-}2.4%; p=0.52) were not significantly changed. However, EEDLW was 209{+/-}83 kcal/d higher during the KD (p=0.023) but was not significantly increased when adjusted for energy balance (EEDLW{Delta}RQ =139{+/-}89 kcal/d; p=0.14). After removing 2 outliers whose EEDLW were incompatible with other data, EEDLW and EEDLW{triangleup}RQ were marginally increased during the KD by 126{+/-}62 kcal/d (p=0.063) and 46{+/-}65 kcal/d (p=0.49), respectively.\n\nConclusionsDLW calculations failing to account for diet-specific energy imbalance effects on RQ erroneously suggest that very low carbohydrate diets substantially increase energy expenditure.

physiology↗