Secular trends and determinants of ad libitum energy intake measured in a research setting from 1999-2020.

Introduction: Historically, secular and seasonal trend analyses have been examined using self-report measures of intake. Rarely are objective measures and known determinants of dietary intake used in these analyses. Our objective was to quantify the seasonal and secular differences in an objective ad libitum intake paradigm while considering the contribution of determinants, such as fat-free mass (FFM) index and spontaneous physical activity (SPA) limited to the restricted space of a whole-room calorimeter. Methods: For this study, recruitment of N = 292 healthy, diabetes free, adults occurred from 1999 to 2020. Assessment during their 10-day stay included body composition (by DXA), SPA (by an approximately 24-h stay in whole-room calorimetry), and ad libitum intake (by a vending machine for 3 days). This secondary analysis used general linear models (GLM) to investigate secular and seasonal differences while adjusting for sex, age, FFM index, FM (fat mass) index, SPA, and race/ethnicity. Results: FFM index and SPA were positively associated with all intake measures (p < 0.05). In all adjusted seasonal models, season did not affect intake. Adjusted secular trends models (kcals/year) demonstrated a decrease in total kcals (ß = -55), intake as percent weight maintaining energy needs (ß = -2), protein kcals (ß = -10), fat kcals (ß = -27), and carbohydrates kcals (ß = -22) (all p < 0.05). After further adjustment for SPA, significance remained in all intake measures (p < 0.05). Secular trends in body composition revealed no changes in weight, BMI, and percent body fat (all p > 0.20). Discussion: Our results indicate that over time, ad libitum intake decreased in this controlled research setting and remained significant even after accounting for positive determinants of intake. A significant ad libitum decrease, coupled with no change in body composition, may highlight a participant bias toward calorie restriction in a controlled setting over time and deserves further investigation.

Acid accumulation is associated with metabolic alterations; higher energy, fat, and protein intake; and energy expenditure.

OBJECTIVE: The objective of this study was to study how acid accumulation (lower plasma bicarbonate and higher anion gap [AG] and corrected anion gap [CAG]) correlates with metabolic parameters, food intake, and 24-h energy expenditure (EE). METHODS: Acid accumulation was measured in 286 healthy adults with estimated glomerular filtration rate > 60 mL/min/1.73 m2. Measurements included body composition by dual-energy x-ray absorptiometry scan, ad libitum energy intake by a vending machine paradigm over 3 days, and 24-h EE in a whole-room indirect calorimeter. RESULTS: Lower bicarbonate, higher AG, and higher CAG were correlated with higher waist and thigh circumferences, body fat (percentage), fat mass, triglycerides, and lower high-density lipoprotein cholesterol. Acid accumulation markers were correlated with higher total energy (CAG partial r = 0.17; p = 0.02), fat (CAG partial r = 0.17; p = 0.02), protein intake (CAG partial r = 0.20; p = 0.006), and 24-h EE (CAG partial r = 0.24; p = 0.0007). A mediation analysis of CAG and total energy intake found that 24-h EE was a partial mediator (40%), but the association remained significant (ß = 0.15; p < 0.0001). CONCLUSIONS: In healthy individuals, acid accumulation was associated with an unfavorable metabolic phenotype; higher 24-h EE; and increased total energy, fat, and protein intake. Acid accumulation markers, as putative markers of higher dietary acid load (e.g., from protein), may affect energy balance physiology promoting weight gain.

Twenty-Four-Hour Urinary Sugars Biomarker in a Vending Machine Intake Paradigm in a Diverse Population.

Accurately measuring dietary sugars intake in large-scale epidemiological studies is necessary to understand dietary sugars' true impact on health. Researchers have developed a biomarker that can be used to assess total sugars intake. Our objective is to test this biomarker in diverse populations using an ad libitum intake protocol. Healthy adult participants (n = 63; 58% Indigenous Americans/Alaska Natives; 60% male; BMI (mean ± SD) = 30.6 ± 7.6 kg.m2) were admitted for a 10-day inpatient stay. On day 2, body composition was measured by DXA, and over the last 3 days, ad libitum dietary intake was measured using a validated vending machine paradigm. Over the same days, participants collected daily 24 h urine used to measure sucrose and fructose. The 24 h urinary sucrose and fructose biomarker (24hruSF) (mg/d) represents the sum of 24 h urinary sucrose and fructose excretion levels. The association between the 3-day mean total sugars intake and log 24uSF level was assessed using the Pearson correlation. A linear mixed model regressing log-biomarker on total sugars intake was used to investigate further the association between biomarker, diet, and other covariates. Mean (S.D.) total sugars intake for the group was 197.7 g/d (78.9). Log 24uSF biomarker was moderately correlated with total sugars intake (r = 0.33, p = 0.01). In stratified analyses, the correlation was strongest in females (r = 0.45, p = 0.028), the 18-30 age group (r = 0.44, p = 0.079), Indigenous Americans (r = 0.51, p = 0.0023), and the normal BMI category (r = 0.66, p = 0.027). The model adjusted for sex, age, body fat percent, and race/ethnicity demonstrated a statistically significant association between 24uSF and total sugars intake (ß = 0.0027, p < 0.0001) and explained 31% of 24uSF variance (marginal R2 = 0.31). Our results demonstrated a significant relationship between total sugars intake and the 24uSF biomarker in this diverse population. However, the results were not as strong as those of controlled feeding studies that investigated this biomarker.

Dietary Adherence Is Associated with Perceived Stress, Anhedonia, and Food Insecurity Independent of Adiposity.

We examined whether perceived stress, anhedonia, and food insecurity were associated with dietary adherence during a 6-week intervention. Sixty participants (23 m; 53 ± 14 y) completed psychosocial measures and were provided with full meals. Individuals with obesity were randomized to a weight-maintaining energy needs (WMENs) (n = 18; BMI 33 ± 4) or a 35% calorie-reduced diet (n = 19; BMI 38 ± 9); normal-weight individuals (n = 23; BMI 23 ± 2) were assigned to a WMENs diet. Adherence scores were determined via weekly assessments and daily ecological momentary assessments (EMAs) of real-time behavior in a natural environment. Perceived stress and anhedonia were associated with % body fat (all r-values > 0.25, all p-values < 0.05), but food insecurity and adherence were not. Higher perceived stress (r = -0.31, p = 0.02), anhedonia (r = -0.34, p = 0.01), and food insecurity (r = -0.27, p = 0.04) were associated with lower adherence scores, even after adjusting for age, sex, and % body fat. In all adjusted models, % body fat was not associated with adherence. Higher measures of stress, anhedonia, and food insecurity predicted lower adherence independently of body fat, indicating that psychosocial factors are important targets for successful adherence to dietary interventions, regardless of body size.

Validation of Total Water Intake from the Automated Self-Administered 24-h Recall, 4-d Food Records, and a Food Frequency Questionnaire Using Doubly Labeled Water.

BACKGROUND: Although prior evidence indicates that water intake is important for health, the ability to accurately measure community-dwelling intake is limited. Only a few studies have evaluated self-reported water intake against an objective recovery biomarker. OBJECTIVES: The aim was to compare preformed water intakes (all sources including food) by multiple Automated Self-Administered 24-h recalls (ASA24s), food frequency questionnaires (FFQs), and 4-d food records (4DFRs) against a recovery biomarker, doubly labeled water (DLW), to assess measurement error. METHODS: Over 1 y, 1082 women and men (50%), aged 50 to 74 y, were asked to complete 6 ASA24s, 2 FFQs, 2 unweighted 4DFRs, and an administration of DLW (n = 686). Geometric means of water intake by self-report tools were compared with DLW. Attenuation factors and correlation coefficients between self-reported and the recovery biomarker (DLW) were estimated. RESULTS: Mean water intakes by DLW were 2777 mL/d (interquartile range, 2350 to 3331) in women and 3243 mL/d (interquartile range, 2720 to 3838) in men. Compared with DLW, water intake was underestimated by 18% to 31% on ASA24s and 43% to 44% on 4DFRs. Estimated geometric means from FFQs differed from DLW by -1% to +13%. For a single ASA24, FFQ, and 4DFR, attenuation factors were 0.28, 0.27, and 0.32 and correlation coefficients were 0.46, 0.48, and 0.49, respectively. Repeated use of 6 ASA24s, 2 FFQs, and 2 4DFRs improved attenuation factors to 0.43, 0.32, and 0.39 and correlation coefficients to 0.58, 0.53, and 0.54, respectively. CONCLUSIONS: FFQs may better estimate population means for usual water intake compared with ASA24 and 4DFR. Similar attenuation factors and correlation coefficients across all self-report tools indicate that researchers have 3 feasible options if the goal is understanding intake-disease relationships. The findings are useful for planning future nutrition studies that set policy priorities for populations and to understand the health impact of water. This trial was registered at clinicaltrials.gov as NCT03268577.

Food insecurity is associated with higher respiratory quotient and lower glucagon-like peptide 1.

OBJECTIVE: Food insecurity is known to be associated with obesity, but its association with physiological measures is unclear. Therefore, it was hypothesized that, compared with food-secure individuals, those with food insecurity would have higher 24-hour energy expenditure (EE [kilocalories per day]) and 24-hour respiratory quotient (RQ [ratio]). Subsequently, hormones involved in appetite regulation, substrate oxidation, and EE were explored. METHODS: A total of 113 healthy participants without diabetes (75 men; mean [SD], age 40 [12] years; BMI 30 [8] kg/m2 ) were included in this analysis. Participants completed the Food Security Short Form, underwent a dual-energy x-ray absorptiometry scan, and spent 24 hours in a human respiratory chamber following a weight-maintaining diet. RESULTS: Compared with individuals with food security, participants with food insecurity had no difference in 24-hour EE. However, they had higher carbohydrate oxidation rates (p = 0.03) and lower lipid oxidation rates (p = 0.02), resulting in higher 24-hour RQ (p < 0.01). They also had lower fasting glucagon-like peptide 1 (p = 0.03) concentrations. CONCLUSIONS: Food insecurity is associated with higher 24-hour RQ and lower fasting glucagon-like peptide 1 concentrations, metabolic and hormonal differences previously shown to drive greater calorie intake in the setting of unrestricted food availability. These findings therefore provide new insight into the paradoxical link between restricted food access and increased adiposity.

Amino Acid Nitrogen Isotope Ratios Respond to Fish and Meat Intake in a 12-Week Inpatient Feeding Study of Men.

BACKGROUND: The natural abundance nitrogen stable isotope ratio (NIR) of whole tissue correlates with animal protein intakes, including meat and fish. Amino acid (AA) NIRs (NIRAAs) are more variable than the whole-tissue NIRs and may thus better differentiate among foods. OBJECTIVES: We evaluated whether NIRAAs were associated with intakes of fish and meat and whether these dietary associations were larger than with whole-tissue NIRs. METHODS: Men were recruited at the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix, Arizona, and randomly assigned to one of eight 12-wk inpatient dietary interventions, which varied the presence/absence of fish, meat, and sugar-sweetened beverages (SSBs) in all possible combinations. Fasting blood was drawn pre- and postintervention and plasma and RBC NIRAAs (free and protein-bound) were measured as secondary outcomes in 32 participants. Multivariable regression was used to determine responses of postintervention NIRAAs to dietary variables, and logistic regression was used to calculate receiver operating characteristic AUCs. RESULTS: Most plasma NIRAAs increased with fish and meat intakes, but to a greater extent with fish intake. The largest increase in response to fish intake was plasma NIRLeucine (ß = 2.19, SE = 0.26). The NIRThreonine decreased with both fish and meat intakes. Fewer RBC NIRAAs increased with fish intake, and only RBC NIRProline increased with meat intake. No plasma or RBC NIRAA responded to SSB intake. We identified fish intake with a high degree of accuracy using plasma NIRLeucine (corrected AUC, cAUC = 0.96) and NIRGlutamic acid/glutamine (cAUC = 0.93), and meat intake to a lower degree using plasma NIRProline (cAUC = 0.80) and RBC NIRProline (cAUC = 0.85). CONCLUSIONS: Plasma and RBC NIRAAs were associated with fish and meat intakes but were not superior to whole-tissue stable isotope biomarkers in identifying these intakes in a US diet. This trial is registered at www.clinicaltrials.gov as NCT01237093.

The counterbalancing effects of energy expenditure on body weight regulation: Orexigenic versus energy-consuming mechanisms.

OBJECTIVE: Weight change is a dynamic function of whole-body energy balance resulting from the interplay between energy intake and energy expenditure (EE). Recent reports have provided evidence for the existence of a causal effect of EE on energy intake, suggesting that increased EE may drive overeating, thereby promoting future weight gain. This study investigated the relationships between ad libitum energy intake and 24-hour EE (24-h EE) in sedentary conditions versus long-term, free-living weight change using a mediation analysis framework. METHODS: Native American individuals (n = 61, body fat by dual-energy x-ray absorptiometry: 39.7% [SD 9.5%]) were admitted to the clinical inpatient unit and had baseline measurements as follows: 1) 24-h EE accurately measured in a whole-room indirect calorimeter during energy balance and weight stability; and 2) ad libitum energy intake objectively assessed for 3 days using computerized vending machines. Free-living weight change was assessed after a median follow-up time of 1.7 years (interquartile range: 1.2-2.9). RESULTS: The total effect of 24-h EE on weight change (-0.23 kg per 100-kcal/d difference in EE at baseline) could be partitioned into the following two independent and counterbalanced effects: higher EE protective against weight gain (-0.46 kg per 100-kcal/d difference in EE at baseline) and an orexigenic effect promoting overeating, thereby favoring weight gain (+0.23 kg per 100-kcal/d difference in EE at baseline). CONCLUSIONS: The overall impact of EE on body weight regulation should be evaluated by also considering its collateral effect on energy intake. Any weight loss intervention aimed to induce energy deficits by increasing EE should take into account any potential orexigenic effects that promote compensatory overeating, thereby limiting the efficacy of these obesity therapies.

Meal-to-meal and day-to-day macronutrient variation in an ad libitum vending food paradigm.

BACKGROUND: Theory posits that macronutrient intake is regulated by protein consumption and adequate intake of protein results in consumption of less carbohydrates and fat. The current study investigates the effect of protein intake on calorie and macronutrient content using an ad libitum vending machine paradigm. METHODS: Healthy volunteers (n = 287; 177 m; Age = 36 ± 11; BMI = 32 ± 8) were admitted to our clinical research unit. Macronutrient meal content (grams) and energy intake (Kcal) were quantified by specialized food processing software and collected on an hourly basis over a three-day period using a validated ad libitum vending machine paradigm. Body composition was assessed by DXA. Lagged multi-level models accounting for age, sex, race/ethnicity, fat and fat free mass indices were fitted to examine the impact of prior macronutrient content on subsequent meals. RESULTS: Protein intake was associated with decreased energy intake (Kcal; B = -1.67 kcal, p = 0.0048), lower protein and carbohydrate intake (B = -0.08 g, p = 0.0006; B = -0.21 g, p = 0.0003, respectively) at subsequent meals. Daily Macronutrient intake and subsequent intake were positively associated. CONCLUSIONS: Dietary protein exhibits a negative regulatory effect on a short-term meal-to-meal rather than day-to-day basis. In the setting of readily available food, protein intake impacts energy intake only over very short time courses.

Food insecurity moderates the relationship between momentary affect and adherence in a dietary intervention study.

OBJECTIVE: Negative affect and food insecurity have been proposed to impede adherence to weight loss interventions. Therefore, this study examined the role of these variables on dietary adherence using Ecological Momentary Assessment. METHODS: A total of 50 participants (19 male participants; age = 49 [SD 14] years) participated in an outpatient dietary study. Lean participants (n = 22; BMI ≤ 25 kg/m2 ) received a weight-maintaining energy needs (WMEN) diet, and participants with obesity (BMI ≥ 30) were randomized to receive either a WMEN diet (n = 14) or a 35% calorie-reduced diet (n = 14). Food insecurity was measured, and, twice daily, Ecological Momentary Assessment captured real-time affect ratings and adherence. Between-person (trait-level) and lagged within-person (state-level) scores were calculated. RESULTS: Greater food insecurity and trait-level negative affect were associated with reduced adherence (p = 0.0015, p = 0.0002, respectively), whereas higher trait-level positive affect was associated with greater adherence (p < 0.0001). Significant interactions between affect and food insecurity revealed an association between higher trait positive affect and increased adherence at lower levels of food insecurity. Higher trait negative affect was more strongly associated with decreased adherence in participants with greater levels of food insecurity (-1 SD: B = -0.21, p = 0.22; mean: B = -0.46, SE = 0.13, p = 0.0004; +1 SD: B = -0.71, SE = 0.17, p < 0.0001). CONCLUSIONS: Trait-level affect may be crucial in predicting dietary adherence, especially in those with greater food insecurity.

Higher fasting plasma FGF21 concentration is associated with lower ad libitum soda consumption in humans.

BACKGROUND: The hepatokine fibroblast growth factor 21 (FGF21) influences eating behavior and sugar consumption in rodent models. However, whether circulating FGF21 concentration is associated with food and soda intake in humans is still unclear. OBJECTIVE: We investigated whether fasting plasma FGF21 concentration is associated with objective measures of ad libitum food intake and soda consumption. METHODS: Healthy individuals [n = 109; 69 men, aged 34 ± 10 y; BMI (kg/m2): 30.4 ± 7.7; body fat by DXA: 30.5% ± 8.9%] with available plasma for hormonal measurements participated in an inpatient cohort study to objectively quantify ad libitum food and soda intake for 3 d using an automated and reproducible vending machine paradigm. Fasting plasma FGF21 concentration was measured by ELISA prior to ad libitum feeding. RESULTS: Fasting FGF21 concentration was inversely associated with daily soda intake (R = -0.22, P = 0.02 adjusted for demographics and anthropometrics), such that an interindividual difference of 200 pg/mL was associated with an average lower soda consumption by 68 kcal/d. Conversely, no associations were observed with total daily energy intake or macronutrient intake (all P > 0.17). CONCLUSIONS: Higher plasma fasting FGF21 concentration is associated with lower ad libitum soda intake. Although this inverse correlation does not imply causation, the present results support the putative role of FGF21 in the reward pathways regulating sugar consumption in humans. This trial was registered at www.clinicaltrials.gov as NCT00342732.

Metabolic Characterization of Meat, Fish, and Soda Intake in Males: Secondary Results from a Randomized Inpatient Pilot Study.

OBJECTIVE: This study aimed to evaluate whether a 12-week, weight-maintaining, macronutrient-stable dietary intervention that varies only by meat, fish, or soda consumption alters 24-hour energy expenditure (24hrEE) and substrate oxidation. METHODS: Healthy males were recruited to participate in a 12-week inpatient study and were randomized to a weight-maintaining dietary intervention that contained varying combinations of meat (0% or 19%), fish (0% or 6%), or soda (0% or 14%) in a factorial design. Macronutrient composition across dietary intervention groups was as follows: 50% of energy from carbohydrates, 30% of energy from fat, and 20% of energy from protein. Whole-room indirect calorimetry at baseline and week 12 were used to measure 24hrEE and substrate oxidation. RESULTS: Twenty-six males (mean [SEM], age: 46.6 [10.4] years; BMI: 26.9 [4.1] kg/m2 ) completed all measurements. Fish consumption resulted in higher 24hrEE by 126 (55) kcal/d compared with no fish consumption (P = 0.03), whereas 24hrEE for soda consumption was 132 (56) kcal/d (P = 0.03) lower. Approximately 80% of the decrease in 24hrEE with soda consumption was due to lower awake-inactive energy expenditure (EE; P = 0.001). No specific EE component accounted for the differences observed with fish consumption. CONCLUSIONS: The data indicate that dietary sources of protein and carbohydrates appear to influence 24hrEE and inactive EE.

The carbon isotope ratios of nonessential amino acids identify sugar-sweetened beverage (SSB) consumers in a 12-wk inpatient feeding study of 32 men with varying SSB and meat exposures.

BACKGROUND: The carbon isotope ratios (CIRs) of individual amino acids (AAs) may provide more sensitive and specific biomarkers of sugar-sweetened beverages (SSBs) than total tissue CIR. Because CIRs turn over slowly, long-term controlled-feeding studies are needed in their evaluation. OBJECTIVE: We assessed the responses of plasma and RBC CIRAA's to SSB and meat intake in a 12-wk inpatient feeding study. METHODS: Thirty-two men (aged 46.2 ± 10.5 y) completed the feeding study at the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix, Arizona. The effects of SSB, meat, and fish intake on plasma and RBC CIRAA's were evaluated in a balanced factorial design with each dietary variable either present or absent in a common weight-maintaining, macronutrient-balanced diet. Fasting blood samples were collected biweekly from baseline. Dietary effects on the postfeeding CIR of 5 nonessential AAs (CIRNEAA's) and 4 essential AAs (CIREAA's) were analyzed using multivariable regression. RESULTS: In plasma, 4 of 5 CIRNEAA's increased with SSB intake. Of these, the CIRAla was the most sensitive (ß = 2.81, SE = 0.38) to SSB intake and was not affected by meat or fish intake. In RBCs, all 5 CIRNEAA's increased with SSBs but had smaller effect sizes than in plasma. All plasma CIREAA's increased with meat intake (but not SSB or fish intake), and the CIRLeu was the most sensitive (ß = 1.26, SE = 0.23). CIRs of leucine and valine also increased with meat intake in RBCs. Estimates of turnover suggest that CIRAA's in plasma, but not RBCs, were in equilibrium with the diets by the end of the study. CONCLUSIONS: The results of this study in men support CIRNEAA's as potential biomarkers of SSB intake and suggest CIREAA's as potential biomarkers of meat intake in US diets. This trial was registered at clinicaltrials.gov/ct2/show/NCT01237093 as NCT01237093.

Reduced metabolic efficiency in sedentary eucaloric conditions predicts greater weight regain in adults with obesity following sustained weight loss.

BACKGROUND: Successful long-term weight loss maintenance after caloric restriction (CR) is rarely achieved. Besides known metabolic, behavioural, and cognitive factors, 24-hour energy expenditure (24hEE) relative to body size (i.e., metabolic efficiency) might influence subsequent weight loss maintenance. METHODS: Eleven participants with obesity (BMI = 39.0 ± 8.7 kg/m2, body fat = 36.1 ± 6.4%) had 24hEE measured in a whole-room indirect calorimeter during eucaloric conditions and weight stability prior to starting a 6-week inpatient CR study (50% of daily energy needs). Twenty-four-hour energy expenditure was adjusted via regression analysis for fat free mass (FFM) and fat mass (FM) by DXA. Body composition was reassessed at the end of CR and after 1-year follow-up. Free-living weight was assessed by monthly weight measurements during 12 months. RESULTS: After 6-week CR, participants lost 8.5 ± 2.7% weight (FFM: -6.3 ± 3.6 kg, FM: -3.4 ± 1.2 kg) but regained 5.1 ± 8.0% 1 year following CR, which was mostly due to FFM regain (+5.7 ± 5.5 kg) and unchanged FM. A relatively higher 24hEE by 100 kcal/day prior to CR was associated with an average greater rate of weight regain by +0.3 kg/month during follow-up and a greater final weight regain by +5.1 kg after 1 year of follow-up. CONCLUSION: These results suggest that reduced metabolic efficiency in 24hEE during eucaloric, sedentary conditions may predict greater weight regain after CR-induced weight loss.

Is Dietary Nonadherence Unique to Obesity and Weight Loss? Results From a Randomized Clinical Trial.

OBJECTIVE: Weight stigma is associated with poor dietary adherence, yet adherence is essential for weight loss and maintenance. This study aimed to determine differences in dietary adherence and perceived hunger between lean individuals and two groups of individuals with obesity. METHODS: In a 6-week outpatient dietary intervention (23 males; aged 48 [SD 14] years), lean participants (n = 23; BMI 23 [SD 2] kg/m2 ) received a weight-maintaining energy needs (WMEN) diet, and participants with obesity (BMI 36 [SD 7]) were randomized to either WMEN (n = 18) or a 35% calorie-reduced (CR) diet (n = 19). All food was provided, and multiple adherence and hunger ratings were assessed daily and weekly on an outpatient basis and in person at twice-weekly visits (e.g., 24-hour recall, diaries). RESULTS: Weight decreased more in the group of CR individuals with obesity (ß = -0.301 kg/wk, P = 0.02) compared with the group of lean individuals and the group of WMEN individuals with obesity. However, total percent adherence did not differ between groups (P = 0.60), and hunger scores did not change across groups over time (P = 0.08). CONCLUSIONS: Results indicate that there are no differences in dietary adherence between lean individuals and individuals with obesity and adherence is not associated with adiposity or hunger. Thus, the belief that nonadherence (e.g., lack of willpower) is unique to obesity is untrue and may perpetuate weight bias and stigma.

Early adaptive thermogenesis is a determinant of weight loss after six weeks of caloric restriction in overweight subjects.

BACKGROUND: Adaptive thermogenesis during prolonged energy deficit refers to the greater than expected reduction in energy expenditure (EE) independent of concomitant loss of metabolically active body mass. OBJECTIVE: As inter-individual variability in the magnitude of adaptive thermogenesis may influence the extent of energy deficit thereby predicting the amount of weight reduction, we investigated whether early adaptive thermogenesis is a determinant of weight loss after 6 weeks of daily 50% caloric restriction in an inpatient setting. DESIGN AND METHODS: The current study reports the results of an exploratory, secondary analysis in overweight but otherwise healthy subjects (n = 11, 7 men, 35 ±â€¯9y, BMI = 40 ±â€¯7 kg/m2, body fat = 63.3 ±â€¯5.3%). Body composition and 24-h EE (24hEE) measurement in a whole-room indirect calorimeter were used to calculate the magnitude of adaptive thermogenesis while on caloric restriction after 1, 3 and 6 weeks. Energy deficit during caloric restriction was quantified via food, stool, and urine bomb calorimetry. Fasting hormonal concentrations (FT4, FT3, FGF21, leptin) were obtained at baseline and at weeks 3 and 6 during caloric restriction. RESULTS: The magnitude of adaptive thermogenesis in 24hEE after 1 week of caloric restriction was -178 ±â€¯137 kcal/day (mean ±â€¯SD), was overall stable during and following caloric restriction, and demonstrated remarkable intra-individual consistency. A relatively greater decrease in 24hEE of 100 kcal/d after 1 week of caloric restriction was associated on average with reduced energy deficit by 8195 kcal over 6 weeks and predicted 2.0 kg less weight loss, of which 0.5 kg was fat mass, after 6 weeks. No correlations were found between hormonal concentrations and weight loss. CONCLUSIONS: The extent of weight loss is influenced by the magnitude of adaptive thermogenesis in the early stage of caloric restriction. Although these results need replication in larger study groups with adequate statistical power, targeting adaptive thermogenesis may help to optimize long-term interventions in obesity therapy.

Thigh Adipocyte Size is Inversely Related to Energy Intake and Respiratory Quotient in Healthy Women.

OBJECTIVE: The relationship between adipocyte size and ad libitum energy intake has not been previously examined. This study hypothesized an inverse relationship between adipocyte size and daily energy intake (DEI). METHODS: Seventy healthy adults (39 men and 31 women; BMI 30.0 [SD 6.3]) underwent dual-energy x-ray absorptiometry and subcutaneous fat biopsies from the abdomen and thigh. Osmium-fixed adipocytes were sized with a Coulter counter. Volunteers self-selected food from a vending machine paradigm as the only source of energy intake over 3 days as inpatients. Volunteers also had 24-hour respiratory quotient (RQ) measured in a whole-room indirect calorimeter. RESULTS: In women, the large cell peak diameter of the thigh depot was greater than that of the abdominal depot (Δ = +15.8 µm; P < 0.0001). In women, thigh peak diameter was inversely associated with DEI (ß = -264.7 kcal/d per 10-µm difference; P = 0.03) after adjusting for demographics and body composition. The thigh peak diameter in women was associated with 24-hour RQ (r = -0.47, P = 0.04) after adjusting for demographics, body composition, and 24-hour energy balance. These associations did not extend to men or the abdominal depot. CONCLUSIONS: In women, thigh adipocyte size was associated with reduced DEI and 24-hour RQ, indicating a special role for thigh fat in women. This depot-specific sexual dimorphism indicates common regulation of energy intake and adipocyte size in the thigh region of women.

Assessing established BMI variants for a role in nighttime eating behavior in robustly phenotyped Southwestern American Indians.

BACKGROUND/OBJECTIVES: Nighttime eating (NE) behavior has a genetic component and predicts weight gain. We hypothesized that some genetic variants, which affect NE would also show an effect on body mass index (BMI). We aimed to determine which known BMI variants associate with NE in Southwestern American Indians (SWAIs), who are at elevated risk for obesity. METHODS: Known BMI variants from the GIANT-UK Biobank meta-analysis (N = 700,000) were analysed in SWAIs characterized for NE during an inpatient 3-day protocol. Variants were analysed for association with NE using whole-genome sequence data from 50 SWAIs (23 cases and 27 controls) and selected variants were genotyped in an additional 32 SWAIs (13 NE cases and 19 controls). Variants associated with NE in a meta-analysis of the two SWAI samples were further analysed for association with nightly caloric intake and functionality in hypothalamus, pituitary, and adrenal tissues. RESULTS: Variants were identified where the allele that associated with increased BMI in the GIANT-UK Biobank meta-analysis (P ≤ 1 × 10-8) also had a P < 0.01 for increased NE in the SWAI meta-analysis. These variants were captured by six tagSNPs. Comparison of the nightly calorie intake by genotype and eQTL data from relevant tissues highlighted rs3753612 upstream of HCRTR1. CONCLUSIONS: Our strategy led to the HCRTR1 locus, which has previously been linked to sleep regulation and feeding. Although this is an intriguing candidate gene for NE, further studies in larger samples and different populations are required to validate the role of HCRTR1 in NE.