Adaptive thermogenesis, at the level of resting energy expenditure, after diet alone or diet plus bariatric surgery.

OBJECTIVE: The objective of this study was to compare the magnitude of adaptive thermogenesis (AT), at the level of resting energy expenditure (REE), after a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy, as well as to investigate the association between AT and changes in appetite. METHODS: A total of 44 participants with severe obesity underwent 10 weeks of a very low-energy diet alone or combined with Roux-en-Y gastric bypass or sleeve gastrectomy. Body weight and composition, REE, subjective appetite feelings, and plasma concentrations of gastrointestinal hormones were measured at baseline and week 11. AT, at the level of REE, was defined as a significantly lower measured versus predicted (using a regression model with baseline data) REE. RESULTS: Participants lost 18.4 ± 3.9 kg of body weight and experienced AT, at the level of REE (-121 ± 188 kcal/day; p < 0.001), with no differences among groups. The larger the AT, at the level of REE, the greater the reduction in fasting ghrelin concentrations and the smaller the reduction in feelings of hunger and desire to eat in the postprandial state. CONCLUSIONS: Weight-loss modality does not seem to modulate the magnitude of AT, at the level of REE. The greater the AT, at the level of REE, the greater the drive to eat following weight loss.

Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance.

There is a substantial body of clinical evidence supporting the beneficial effects of lower-carbohydrate dietary patterns on multiple established risk factors associated with insulin resistance and cardiovascular diseases in adult populations. Nutrition and health researchers, clinical practitioners, and stakeholders gathered for, "The Scientific Forum on Nutrition, Wellness, and Lower-Carbohydrate Diets: An Evidence- and Equity-Based Approach to Dietary Guidance" to discuss the evidence base around lower-carbohydrate diets, health outcomes, and dietary guidance. Consensus statements were agreed upon to identify current areas of scientific agreement and spotlight gaps in research, education, and practice to help define and prioritize future pathways. Given the evidence base and considering that most American adults are living with at least one nutrition-related chronic disease, there was consensus that including a lower-carbohydrate dietary pattern as one part of the Dietary Guidelines for Americans could help promote health equity among the general population.

Metabolic adaptation is associated with a greater increase in appetite following weight loss: a longitudinal study.

BACKGROUND: Weight loss is associated with a disproportionate reduction in energy expenditure, along with increases in hunger feelings and ghrelin concentrations. These changes are presumed to be homeostatic mechanisms to counteract the energy deficit. The possibility that these 2 components of the energy balance equation are mechanistically linked has never been examined. OBJECTIVE: This study aimed to determine if the disproportionate reduction in resting metabolic rate (RMR) seen with weight loss is associated with changes in the plasma concentration of gastrointestinal hormones involved in appetite regulation and subjective appetite ratings. METHODS: This was a longitudinal study with repeated measurements. Fifty-six individuals with obesity (body mass index [BMI]: 34.5±0.5 kg/m2; age: 47±1 y; 26 males) underwent an 8 wk low-energy diet, followed by 4 wk of refeeding and weight stabilization. The RMR, respiratory quotient (RQ), body composition, plasma concentrations of ghrelin, glucagon-like peptide 1, peptide YY, cholecystokinin, insulin, and appetite ratings in the fasting and postprandial states were measured at baseline, Wk9 and 13. Metabolic adaptation was defined as significantly lower when measured versus the predicted RMR (pRMR) (from own regression model using baseline data). RESULTS: A 14.2±0.6 kg weight loss was seen at Wk9 and maintained at Wk13. RQ was significantly reduced at Wk9 (0.82±0.06 vs. 0.76±0.05, P< 0.001) but returned to baseline at Wk13. Metabolic adaptation was seen at Wk9, but not Wk13 (-341±58, P <0.001 and -75±72 kJ/d, P = 0.305, respectively). The larger the difference between measured and predicted RMR at both timepoints, the greater the increase in hunger, desire to eat, and composite appetite score (fasting and postprandial at Wk9, postprandial only at Wk13), even after adjusting for weight loss and RQ. CONCLUSION: A larger metabolic adaptation during weight loss is accompanied by a greater drive to eat. This might help explain the interindividual differences in weight loss outcomes to dietary interventions.

The Effects of COVID-19 Virtual Learning on Body Fat and Insulin Resistance in Adolescents with Overweight or Obesity.

(1) Background: COVID-19 virtual learning reduced structural supports for adolescent physical activity and diet, threatening metabolic health, especially in teens with overweight or obesity (OWOB). (2) Methods: Adolescents (N = 14) with OWOB completed fasting blood draws (measuring insulin resistance, IR) and Dual Energy X-Ray Absorptiometry (DXA, measuring total body fat percent, TBF%) pre-COVID-19 and during COVID-19. Changes in TBF% and IR were calculated (1) pre-COVID-19 and (2) from pre-COVID-19 to during COVID-19. Age and body mass index (BMI) percentile-matched data assessed normative changes across similar, non-COVID-19 time periods. Paired t-tests compared TBF% change pre- to during COVID-19 with (1) TBF% change pre-COVID19 and (2) TBF% normative change. Two ANCOVAs compared IR change pre- to during COVID-19 with (1) IR change pre-COVID-19 controlling for BMI z-score and difference in time between assessments and (2) normative change in IR controlling for sex/race. (3) Results: The TBF% change pre-COVID-19 and the normative change were similar. The TBF% increased more (~six percentage points) during COVID-19 compared to normative change (p < 0.01). During COVID-19, IR increased more (~2.5 units) than change pre-COVID-19 (p = 0.03) and increased more (~3.5 units) than normative change (p = 0.01). (4) Conclusions: TBF% and IR increased exponentially during COVID-19 in teens with OWOB compared to pre-COVID-19 and normative changes.

Systemic Inflammation, Endothelial Function, and Risk of Periodontitis in Overweight/Obese Adults.

The network interaction between systemic inflammatory mediators, endothelial cell adhesion function, and adiponectin as mediators of the association between metabolic diseases and periodontitis has not been evaluated. The objective of this study is to assess whether the interaction of baseline serum levels of TNF-α, hs-CRP, ICAM-1, VCAM-1, and adiponectin leads to periodontitis. Five hundred and ninety-seven overweight/obese (overweight: BMI 25 to <30 kg/m2; obese: >30 kg/m2) adults, aged 40-65 years, with complete 3-year follow-up data were included. Generalized structural equation models with negative binomial regression were used to estimate the regression coefficient (ß) for the outcome number of teeth with probing pocket depth (PPD) ≥ 4 mm and bleeding on probing (BOP) at 3-year follow-up for a 1 standard deviation unit increase (Δ = +1SD) in each biomarker. After adjusting for multiple covariates, baseline ICAM-1 and VCAM-1 had significant direct effects on increased log-transformed number of teeth with PPD ≥ 4 mm and BOP (ß: 0.16; 95% CI: 0.02-0.30; ß: 0.15; 95% CI: 0.02-0.30, respectively). Baseline hs-CRP showed a significant indirect effect via ICAM-1 on the log-transformed number of teeth with PPD ≥ 4 mm and BOP (ß: 4.84; 95% CI: 0.27-9.42). Thus, elevated serum ICAM-1 and VCAM-1 have a significant direct effect and increased hs-CRP has a significant indirect effect on the predicted level of periodontitis at the 3-year follow-up among overweight/obese Hispanic adults.

Association between ß-Hydroxybutyrate Plasma Concentrations after Hypocaloric Ketogenic Diets and Changes in Body Composition.

BACKGROUND: Early studies show that ketogenic diets (KDs) lead to preferential loss of fat mass (FM), whereas preserving fat-free mass (FFM). Additionally, animal data support the anticatabolic effects of DL-3-hydroxybutyrate. From our knowledge, a potential association between ß-hydroxybutyrate (ßHB) plasma concentrations and changes in body composition has never been explored. OBJECTIVES: The main aim of this analysis was to determine if ßHB plasma concentrations, following hypocaloric KDs, were associated with FM and FFM changes in men and women with obesity. METHODS: Data from 199 individuals (BMI = 36.6 ± 4.3 kg/m2; age = 43.6 ± 9.8 y; 82 men) were collated from 3 weight loss studies employing common measures of body composition (air displacement plethysmography) and ßHB plasma concentration (ELISA). The association between ßHB and weight, FM and FFM loss (kg), and %FFM loss (%FFML) was investigated with Spearman correlation. Multivariable linear regression was used to determine if ßHB was a significant predictor of the changes in anthropometric variables, after adjusting for confounding factors. RESULTS: ßHB was not associated with FFML (% or kg), but a weak positive association was seen with FM loss (r = 0.182, P = 0.01, n = 199) and a trend with weight loss (r = 0.128, P = 0.072, n = 199). ßHB was a significant predictor of both weight and FM loss (kg), after adjusting for age, sex, baseline BMI, and intervention study. CONCLUSIONS: The magnitude of ketosis is not associated with FFM preservation. However, the higher the level of ketosis, the greater the weight and FM loss. Further studies are needed to confirm these findings and to explore the mechanisms involved. This trial was registered at clinicaltrials.gov identifier as NCT01834859, NCT04051190, NCT02944253.

Associations of renal sinus fat with blood pressure and ectopic fat in a diverse cohort of adults.

Background: Renal sinus fat (RSF) is an ectopic fat depot shown to be associated with visceral adiposity and hypertension in predominantly white populations. The purpose of this analysis is to investigate RSF and associations between RSF and blood pressure in a cohort of African American (AA) and European American (EA) adults. A secondary purpose was to explore risk factors associated with RSF. Methods: Participants were 116 A A and EA adult men and women. Ectopic fat depots were assessed with MRI: RSF, intraabdominal adipose tissue (IAAT), intermuscular adipose tissue (IMAT), perimuscular adipose tissue (PMAT), and liver fat. Cardiovascular measures included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure, mean arterial pressure, and flow mediated dilation. Matsuda index was calculated for insulin sensitivity. Pearson correlations were used to investigate associations of RSF with cardiovascular measures. Multiple linear regression was used to evaluate contributions of RSF on SBP and DBP and to explore factors associated with RSF. Results: No difference was observed in RSF between AA and EA participants. RSF was positively associated with DBP in AA participants, but this was not independent of age and sex. Age, male sex, and total body fat were positively associated with RSF in AA participants. Insulin sensitivity was inversely and IAAT and PMAT were positively associated with RSF in EA participants. Conclusions: Differential associations of RSF with age, insulin sensitivity, and adipose depots among AA and EA adults suggest unique pathophysiological mechanisms influence RSF deposition, which may contribute to chronic disease etiology and progression.

Associations of atrial natriuretic peptide with measures of insulin and adipose depots.

Low concentrations of natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). African American individuals (AA) have lower NP levels and are disproportionately burdened by T2D. The purpose of this study was to test the hypothesis that higher post-challenge insulin in AA adults is associated with lower plasma N-terminal pro-atrial natriuretic peptide (NT-proANP). A secondary purpose was to explore associations between NT-proANP and adipose depots. Participants were 112 AA and European American (EA) adult men and women. Measures of insulin were obtained from an oral glucose tolerance test and hyperinsulinemic-euglycemic glucose clamp. Total and regional adipose depots were measured from DXA and MRI. Multiple linear regression analysis was used to assess associations of NT-proANP with measures of insulin and adipose depots. Lower NT-proANP concentrations in AA participants was not independent of 30-min insulin area under the curve (AUC). NT-proANP was inversely associated with 30-min insulin AUC in AA participants, and with fasting insulin and HOMA-IR in EA participants. Thigh subcutaneous adipose tissue and perimuscular adipose tissue were positively associated with NT-proANP in EA participants. Higher post-challenge insulin may contribute to lower ANP concentrations in AA adults.

Association between Fat-Free Mass Loss, Changes in Appetite, and Weight Regain in Individuals with Obesity.

BACKGROUND: The role of fat-free mass loss (FFML) in modulating weight regain in individuals with obesity, as well as the potential mechanisms involved, remain inconsistent. OBJECTIVES: The aim of this study was to determine if % FFML following weight loss (WL) is a predictor of weight regain and to investigate the association between %FFML and changes in appetite markers. METHODS: Seventy individuals with obesity (BMI: 36 ± 4 kg/m2; age: 44 ± 9 y; 29 males) underwent 8 wk of a very low energy diet (550-660 kcal/d), followed by 4 wk of gradual refeeding and weight stabilization and a 9-mo maintenance program (eucaloric diet). The primary outcomes were body weight and body composition (fat mass and fat-free mass). The secondary outcomes were plasma concentrations of ß-hydroxybutyrate (a marker of ketosis) in fasting and appetite-related hormones (ghrelin, glucagon-like peptide 1, peptide YY, and cholecystokinin) and subjective appetite feelings during fasting and every 30 min after a fixed breakfast for 2.5 h. All were measured at baseline, week 9, and 1 y [week 13 in 35 subjects (25 males)]. The association between FFML, weight regain, and changes in appetite was assessed by linear regression. RESULTS: WL at week 9 was 17.5 ± 4.3kg and %FFML 20.4 ± 10.6%. Weight regain at 1 y was 1.7 ± 8.2 kg (8.8 ± 45.0%). After adjusting for WL and fat mass at baseline, %FFML at week 9 was not a significant predictor of weight regain. Similar results were seen at week 13. The greater the %FFML at week 9, but not 13, the smaller the reduction, or greater the increase in basal ghrelin concentration (ß: -3.2; 95% CI: -5.0, -1.1; P = 0.003), even after adjusting for WL and ß-hydroxybutyrate. CONCLUSIONS: %FFML was not a significant predictor of weight regain at 1 y in individuals with obesity. However, a greater %FFML was accompanied by a greater increase in ghrelin secretion under ketogenic conditions, suggesting a link between fat-free mass and appetite regulation. This trial was registered at clinicaltrials.gov as NCT01834859.

Proinsulin-to-C-Peptide Ratio as a Marker of ß-Cell Function in African American and European American Adults.

OBJECTIVE: The primary purpose of the current study was to test the hypothesis that the proinsulin-to-C-peptide (PI-to-CP) ratio, as an index of proinsulin secretion, would be higher and associated with indices of ß-cell function in African American adults relative to European American adults without type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants were 114 African American and European American adult men and women. A 2-h oral glucose tolerance test was conducted to measure glucose, insulin, C-peptide, and proinsulin and derive indices of ß-cell response to glucose. The Matsuda index was calculated as a measure of insulin sensitivity. The disposition index (DI), the product of insulin sensitivity and ß-cell response, was calculated for each phase of ß-cell responsivity. Pearson correlations were used to investigate the relationship of the PI-to-CP ratio with each phase of ß-cell response (basal, Φb; dynamic, Φd; static, Φs; total, Φtot), disposition indices (DId, DIs, DItot), and insulin sensitivity. Multiple linear regression analysis was used to evaluate independent contributions of race, BMI, and glucose tolerance status on PI-to-CP levels before and after adjustment for insulin sensitivity. RESULTS: African American participants had higher fasting and 2-h PI-to-CP ratios. The fasting PI-to-CP ratio was positively associated with Φb, and the fasting PI-to-CP ratio and 2-h PI-to-CP ratio were inversely associated with DId and insulin sensitivity only in African American participants. CONCLUSIONS: The PI-to-CP ratio could be useful in identifying African American individuals at highest risk for ß-cell dysfunction and ultimately type 2 diabetes.

Inflammation, Executive Function, and Adiposity in Children With or at Risk for Obesity: A Pilot Study.

OBJECTIVE: Obesity is associated with executive function (EF) deficits across the lifespan. Higher body mass index (BMI), obesity severity, and poorer adherence and weight outcomes in obesity treatment have all been associated with EF deficits. Adult literature has begun to emphasize neuroinflammation in obesity as a possible pathway to later cognitive impairment in EF. However, pediatric obesity literature has yet to establish associations between peripheral inflammation and EF. Thus, the present study examined associations and variability in inflammation, EF, and adiposity in children with or at risk for obesity. Additionally, inflammation was examined as a mediator of the relationship between adiposity and EF. METHODS: Children (N = 39) aged 8-12 years with BMI ≥ 50th percentile were recruited. The NIH Toolbox Cognitive Battery was used to assess performance-based EF. Peripheral inflammation was assessed in fasted sera. Dual-energy X-ray absorptiometry scans were conducted to assess body composition. Linear regression and Hayes' PROCESS Model 4 (Hayes, 2017) were used to evaluate associations between adiposity and inflammation, inflammation and EF, and whether adiposity effects EF through its effect on inflammation. RESULTS: Positive associations were identified between adiposity and inflammation, and negative to null associations were identified between inflammation and EF. Medium indirect effects of adiposity on EF through inflammation were detected. CONCLUSION: Pilot evidence suggests greater adiposity is linked with greater inflammation, which in turn is associated with less EF in some domains. Directionality and causality cannot yet be established, but with replication, findings may inform efforts to target EF in pediatric obesity.

Association between Fat-Free Mass Loss after Diet and Exercise Interventions and Weight Regain in Women with Overweight.

PURPOSE: This study aimed to determine if percent fat-free mass loss (% FFML) after diet alone, diet plus aerobic, or diet plus resistance exercise is a predictor of weight regain in women with overweight. METHODS: One hundred and forty-one premenopausal women with overweight (body mass index, 28 ± 1 kg·m -2 ; age, 35 ± 6 yr) enrolled in a weight loss program to achieve a body mass index <25 kg·m -2 (diet alone, diet plus resistance, or diet plus aerobic exercise) and were followed for 1 yr. Body weight and composition (with dual-energy x-ray absorptiometry) were measured at baseline, after weight loss, and at 1 yr. RESULTS: Participants lost 12.1 ± 2.6 kg of body weight, 11.3 ± 2.5 kg of fat mass, and 0.5 ± 1.6 kg of fat-free mass during the weight loss intervention, followed by weight regain at 1 yr (6.0 ± 4.4 kg, 51.3% ± 37.8%; P < 0.001 for all). % FFML was -3.6 ± 12.4, and a greater % FFML was associated with more weight regain ( r = -0.216, P = 0.01, n = 141), even after adjusting for the intervention group ( ß = -0.07; 95% confidence interval, -0.13 to -0.01; P = 0.017). CONCLUSIONS: % FFML is a significant predictor of weight regain in premenopausal women with overweight. These results support strategies for conserving fat-free mass during weight loss, such as resistance training. Future research should try to identify the mechanisms, at the level of both appetite and energy expenditure, responsible for this association.

Metabolic adaptation delays time to reach weight loss goals.

OBJECTIVE: The aim of this study was to determine whether metabolic adaptation, at the level of resting metabolic rate, was associated with time to reach weight loss goals, after adjusting for confounders. METHODS: A total of 65 premenopausal women with overweight (BMI: 28.6 ± 1.5 kg/m2 ; age: 36.4 ± 5.9 years; 36 were White, and 29 were Black) followed an 800-kcal/d diet until BMI ≤25 kg/m2 . Body weight and composition were measured at baseline and after weight loss. Dietary adherence was calculated from total energy expenditure, determined by double labeled water, and body composition changes. Metabolic adaptation was defined as a significantly lower measured versus predicted resting metabolic rate (from own regression model). A regression model to predict time to reach weight loss goals was developed including target weight loss, energy deficit, dietary adherence, and metabolic adaptation as predictors. RESULTS: Participants lost on average 12.5 ± 3.1 kg (16.1% ± 3.4%) over 155.1 ± 49.2 days. Average dietary adherence was 63.6% ± 31.0%. There was significant metabolic adaptation after weight loss (-46 ± 113 kcal/d, p = 0.002) and this variable was a significant predictor of time to reach weight loss goals (ß = -0.1, p = 0.041), even after adjusting for confounders (R2 adjusted = 0.63, p < 0.001). CONCLUSION: In premenopausal women with overweight, metabolic adaptation after a 16% weight loss increases the length of time necessary to achieve weight loss goals.

Bioimpedance-Derived Membrane Capacitance: Clinically Relevant Sources of Variability, Precision, and Reliability.

Membrane capacitance (CM), a bioimpedance-derived measure of cell membrane health, has been suggested as an indicator of health status. However, there are few published data to support its use in clinical settings. Hence, this study evaluated clinically relevant sources of variation, precision, and reliability of CM measurements. This longitudinal study included 60 premenopausal women. Sources of variability (e.g., demographics, body composition, serum measures, diet) were identified by stepwise regression. Precision and reliability were assessed by the coefficient of variation (CV), intraclass correlation coefficients (ICC), and technical error of the measurement (TEM) for intra-day (30 min apart) and inter-day measurements (7-14 days apart). Body composition, temperature, and metabolic activity were identified as sources of variability. CM measurements had high precision (CV = 0.42%) and high reliability for intra-day (ICC = 0.996) and inter-day (ICC = 0.959) measurements, independent of menstrual cycle and obesity status. Our results showed that CM measurements are sensitive to clinical factors and have high precision and reliability. The results of this study suggest that CM is sufficiently reliable for health status monitoring in conditions with variation in body composition, metabolic activity, or body temperature among premenopausal women.

Interaction effect of systemic inflammation and modifiable rheumatoid cachexia risk factors on resting energy expenditure in patients with rheumatoid arthritis.

Background: In rheumatoid cachexia (RC), high resting energy expenditure (REE) is associated with loss of muscle mass driven by proinflammatory cytokines. The objectives of this study were to investigate parameters associated with RC, and the interaction between systemic inflammation and modifiable risk factors for RC on REE. Methods: Thirty-five rheumatoid arthritis (RA) and nineteen non-RA controls comparable in age, sex, race and BMI underwent measures of REE by indirect calorimetry. Clinical, dietary, body composition and physical function data were collected. Homeostasis model assessment for insulin resistance (HOMA-IR) and serum interleukin-6 (IL-6) were used as parameters of IR and systemic inflammation, respectively. Regression models tested association between REE and dependent variables, including pre-specified interaction tests involving HOMA-IR and IL-6 and dietary intake of protein per weight (PPW) and IL-6. Results: RA subjects were mostly women (94%) and had a median age of 54 years (50.5, 70) and BMI of 30.5 kg/m2 (26.1, 36.9). We observed a significant interaction effect between PPW and serum IL-6 on REE among RA subjects in the multiple regression model among RA. The upper tertile of PPW demonstrated a significant negative correlation between REE and IL-6 (ß=-19.97, 95% CI [-35.41, -4.54], p=0.01). The lower tertile of PPW demonstrated a significant positive correlation between REE and IL-6 (ß=42.24, 95% CI [4.25, 80.23], p=0.03). Conclusions: While IR can lead to muscle catabolism, IR was not significantly associated with REE in RA individuals. Higher dietary protein intake could attenuate the effect of systemic inflammation on REE in RA patients.

Sex and race contribute to variation in mitochondrial function and insulin sensitivity.

OBJECTIVE: Insulin sensitivity is lower in African American (AA) versus Caucasian American (CA). We tested the hypothesis that lower insulin sensitivity in AA could be explained by mitochondrial respiratory rates, coupling efficiency, myofiber composition, or H2 O2 emission. A secondary aim was to determine whether sex affected the results. METHODS: AA and CA men and women, 19-45 years, BMI 17-43 kg m2 , were assessed for insulin sensitivity (SIClamp ) using a euglycemic clamp at 120 mU/m2 /min, muscle mitochondrial function using high-resolution respirometry, H2 O2 emission using amplex red, and % myofiber composition. RESULTS: SIClamp was greater in CA (p < 0.01) and women (p < 0.01). Proportion of type I myofibers was lower in AA (p < 0.01). Mitochondrial respiratory rates, coupling efficiency, and H2 O2 production did not differ with race. Mitochondrial function was positively associated with insulin sensitivity in women but not men. Statistical adjustment for mitochondrial function, H2 O2 production, or fiber composition did not eliminate the race difference in SIClamp . CONCLUSION: Neither mitochondrial respiratory rates, coupling efficiency, myofiber composition, nor mitochondrial reactive oxygen species production explained lower SIClamp in AA compared to CA. The source of lower insulin sensitivity in AA may be due to other aspects of skeletal muscle that have yet to be identified.

Association between ketosis and metabolic adaptation at the level of resting metabolic rate.

BACKGROUND: The ketone body ß-hydroxybutyrate (ßHB) has been shown to act as a signaling molecule that regulates metabolism and energy homeostasis during starvation in animal models. A potential association between ßHB and metabolic adaptation (a reduction in energy expenditure below predicted levels) in humans has never been explored. OBJECTIVE: To determine if metabolic adaptation at the level of resting metabolic rate (RMR) was associated with the magnitude of ketosis induced by a very-low energy diet (VLED). A secondary aim was to investigate if the association was modulated by sex. METHODS: Sixty-four individuals with obesity (BMI: 34.5 ± 3.4 kg/m2; age: 45.7 ± 8.0 years; 31 males) enrolled in a 1000 kcal/day diet for 8 weeks. Body weight/composition, RMR and ßHB (as a measure of ketosis) were determined at baseline and week 9 (W9). Metabolic adaptation was defined as a significantly lower measured versus predicted RMR (from own regression model). RESULTS: Participants lost on average 14.0 ± 3.9 kg and were ketotic (ßHB: 0.76 ± 0.51 mM) at W9. A significant metabolic adaptation was seen (-84 ± 106 kcal/day, P < 0.001), with no significant differences between sexes. [ßHB] was positively correlated with the magnitude of metabolic adaptation in females (r = 0.432, P = 0.012, n = 33), but not in males (r = 0.089, P = 0.634, n = 31). CONCLUSION: In females with obesity, but not males, the larger the [ßHB] under VLED, the greater the metabolic adaptation at the level of RMR. More studies are needed to confirm these findings and to explore the mechanisms behind the sex difference in the association between ketosis and metabolic adaptation. TRIAL REGISTRATION NAME: Clinicaltrials.gov. STUDY REGISTRATION ID: NCT02944253. URL: https://clinicaltrials.gov/ct2/show/NCT02944253.

A Pilot Study of Associations Between Visceral Fat, IL-6, and Urinary F2-Isoprostanes in Older Adults Exposed to a Diet Intervention.

BACKGROUND: Short-term markers of successful visceral adipose tissue (VAT) loss are needed. Urinary F2-isoprostanes might serve as a marker for intensified lipid metabolism, whereas circulating IL-6 might stimulate fat oxidation and enhance mobilization of VAT. OBJECTIVES: This pilot study was designed to explore the hypotheses that 1) reduction in VAT is associated with increase in IL-6, and 2) that increases in urinary F2-isoprostanes are associated with increases in IL-6 and reduction in VAT. METHODS: Eighteen participants (aged 60-75 y, BMI 30-40 kg/m2) were randomly assigned to either a very-low-carbohydrate diet (VLCD; <10:25:>65% energy from carbohydrate:protein:fat) or a low-fat diet (LFD; 55:25:20%) for 8 wk. Changes in fat distribution were assessed by MRI. Four urinary F2-isoprostane isomers were quantified in 24-h urine collection using LC-MS/MS analyses. Changes in 4 F2-isoprostane isomers were summarized using factor analysis (Δ-F2-isoprostane factor). Statistical significance was set at P < 0.1. RESULTS: Within the VLCD group, change in VAT was inversely associated with change in IL-6 (r = -0.778, P = 0.069) and Δ-F2-isoprostane factor (r = -0.690, P = 0.086), demonstrating that participants who maintained higher concentrations of F2-isoprostane factor across the intervention showed greater decreases in VAT. A positive relation between Δ-F2-isoprostane factor and change in IL-6 was observed (r = 0.642, P = 0.062). In the LFD group, no significant associations between changes in VAT, F2-isoprostane factor, or IL-6 were observed. CONCLUSIONS: Results from this exploratory study in older adults with obesity suggest that, in the context of a VLCD, IL-6 could be involved in VAT mobilization, and urinary F2-isoprostanes could reflect intensified oxidation of mobilized fatty acids.Trial registration: This study is registered at clinicaltrials.gov as NCT02760641.

Genetic risk score prediction of leg fat and insulin sensitivity differs by race/ethnicity in early pubertal children.

BACKGROUND: In the United States, the underlying reasons for racial/ethnic disparities in type 2 diabetes risk remain unclear. However, differences in genetic risk for insulin resistance and peripheral adipose tissue distribution may be contributing factors. OBJECTIVE: To investigate racial/ethnic differences in associations of genetic risk for insulin resistance with leg fat and insulin sensitivity in a cohort of American children. METHODS: Participants were healthy European-American (n = 83), African-American (n = 79) and Hispanic-American (n = 74) children aged 7-12 years. Genetic risk scores were derived from published variants associated with insulin resistance phenotypes in European adults. Body composition was assessed using dual-energy X-ray absorptiometry. Insulin sensitivity was determined from the frequently sampled intravenous glucose tolerance test and minimal modelling. Statistical models were adjusted for age, sex, pubertal stage and body composition. RESULTS: In the combined cohort, risk score was inversely associated with insulin sensitivity (p = 0.033) but not leg fat (p = 0.170). Within Hispanic Americans, risk score was inversely associated with insulin sensitivity (p = 0.027) and leg fat (p = 0.005), while associations were non-significant in European and African Americans (p > 0.200). CONCLUSIONS: The higher type 2 diabetes risk observed among Hispanic Americans may have a genetic basis related to an inability to store lipid in peripheral adipose tissue.