Regional Adiposity Research Articles

The associations between body fat distribution and bone mineral density in the Oxford Biobank: a cross sectional study

ABSTRACT Background Body composition is associated with bone mineral density (BMD), but the precise associations between body fat distribution and BMD remain unclear. The regional adipose tissue depots have different metabolic profiles. We hypothesized that they would have independent associations with BMD. Research Design and Methods We used data from 4,900 healthy individuals aged 30–50 years old from the Oxford Biobank to analyze associations between regional fat mass, lean mass and total BMD. Results Total lean mass was strongly positively associated with BMD. An increase in total BMD was observed with increasing mass of all the fat depots, as measured either by anthropometry or DXA, when accounting for lean mass. However, on adjustment for both total fat mass and lean mass, fat depot specific associations emerged. Increased android and visceral adipose tissue mass in men, and increased visceral adipose tissue mass in women, were associated with lower BMD. Conclusions Fat distribution alters the association between adiposity and BMD.

The relationship of regional abdominal adiposity and adiposity‐related factors with cognitive functioning among middle‐aged individuals at high Alzheimer’s dementia risk

AbstractBackgroundObesity in midlife has been consistently associated with late‐life cognitive decline and Alzheimer’s dementia (AD). Obesity is typically assessed by body mass index (BMI) rather than specific anatomical location of stored excess fat. These fat depots can affect the secretion of adipose‐related factors that in turn may affect AD risk. In this study we examined whether regional abdominal adiposity and adiposity‐related secreted factors are related to cognition in middle‐aged adults at high AD risk due to a parental history of AD.MethodParticipants were from The Israel Registry for Alzheimer’s Prevention (IRAP) study following middle‐aged offspring of Late‐Onset AD patients (N=390). To date, 46 participants who have complete cognitive assessment (summarized as global cognition and four cognitive domains—episodic memory, executive functions, language and working memory) have also been scanned for hepatic and pancreatic adiposity, and abdominal adipose tissue (AAT) via magnetic resonance imaging (MRI). Adiposity‐related factors primarily secreted by the liver (PAI‐1), visceral fat (TNF‐α), and the pancreas (PYY) were quantified by MILLIPLEX® MAP for 26 participants. Linear regressions examined the association of regional fat and adiposity‐related factors with cognition adjusting for age, sex, education, and BMI.ResultParticipants (52% women) averaged 51.5 (SD=5.5) years of age, 17.3 (SD=2.1) years of education. Higher AAT was associated with lower global cognition (r=‐0.347, p=0.024), executive function (r=‐0.471, p=0.024) and approached significance for language (r=‐0.301, p=0.053). Higher hepatic fat was associated with lower executive functions (r=‐0.334, p=0.031) and the association of higher pancreatic fat with poorer executive function approached significance (r=‐0.273, p=0.081). All three adipose‐related secreted factors were associated with lower executive functions (PAI1 (r=‐0.635, p=0.003), TNF‐α (r=‐0.478, p=0.033) and PYY (r=‐0.420, p=0.065)) but not with global cognition or other cognitive domains.ConclusionHigher regional abdominal adiposity and related secreted factors were associated with poorer cognitive functions, especially executive functions, already in midlife, in asymptomatic individuals enriched for AD risk, and regardless of global body fat measured by BMI. By AAIC 2021, we anticipate 100 IRAP participants will be assessed for regional abdominal adiposity and adipose‐related factors. Targeting regional adiposity is expected to prevent or delay cognitive decline, and ultimately AD.

Regional abdominal adiposity is associated with BMI‐related brain regions in middle‐aged adults at high risk of Alzheimer’s dementia

AbstractBackgroundThere is evidence for the involvement of midlife obesity in mild cognitive impairment (MCI), dementia, and Alzheimer’s dementia (AD) risk in late life. Obesity is primarily measured by body mass index (BMI), which poorly reflects body fat distribution. Regional abdominal adiposity has been related to inflammation and metabolic syndrome, both consistently linked to the neuropathology of AD and related disorders (ADRD). We examined the relationship between regional abdominal adiposity and regional brain volume, among middle‐aged adults enriched for AD risk due to parental history of AD.MethodParticipants were from the Israel Registry for Alzheimer’s Prevention (IRAP), which follows middle‐aged offspring of AD patients (N=390). At this time, 44 participants (Table 1) were scanned, via magnetic resonance imaging (MRI), for regional abdominal adiposity, including hepatic, pancreatic, and abdominal adipose tissues (AAT, visceral (VAT), and subcutaneous (SAT)). T1‐weighted volumetric brain MRI focused on three regions implicated in obesity and cognitive impairment: para‐hippocampus, amygdala, and inferior frontal gyrus (IFG). Following logarithmic normalization, linear regression was used to examine the association of regional abdominal fat with brain volume adjusting for age, sex, education, and intracranial volume. An additional adjustment for BMI was done to examine whether the associations are above and beyond global adiposity.ResultSmaller amygdalar volume was associated with the percentage of VAT fat (r=‐0.324, p=0.044) and approached significance for pancreatic (r=‐0.283, p=0.08) and hepatic (r=‐0.307, p=0.057) fat. A smaller para‐hippocampal volume was associated with the percentage of pancreatic fat (r=‐0.317, p=0.05) and hepatic (r=‐0.447, p=0.004) fat, and approached significance for VAT fat (r=‐0.309, p=0.056). Fat percentage was not associated with IFG volume (Table 2; Figure 1).ConclusionGreater regional abdominal adiposity was associated with higher amygdalar and para‐hippocampal volumes, already in midlife, regardless of global body adiposity measured by BMI. Regional adiposity affects secreted factors relevant to brain function, suggesting an underlying mechanism. By AAIC 2021, we anticipate 100 IRAP participants will be assessed for regional abdominal adiposity, blood‐based related secreted factors, and brain MRI. These data may lead to the development of age‐specific interventions targeting specific adipose depots, which are expected to prevent or delay neuropathology, cognitive decline, and ultimately AD.

Regional abdominal adiposity and related factors are associated with brain volumes and cognitive functioning in middle‐aged adults at high AD‐risk

AbstractBackgroundAlzheimer’s dementia (AD) is one of the most challenging diseases, affecting individuals, their families, and society. There is evidence for the involvement of midlife obesity (measured by BMI) in mild cognitive impairment (MCI), dementia, and AD risk in late life. Regional abdominal adiposity has been related to metabolic syndrome and inflammation, both consistently linked to cognitive impairment and neuropathology of AD. The accelerating prevalence of obesity and dementia in our aging population further amplifies the potential public health impact of the proposed investigation.MethodThe Israel Registry for Alzheimer’s Prevention (IRAP) (N=500), which aims to examine the connection between longevity and dementia, was capitalized. Newly collected data ‐ regional abdominal adiposity (abdominal (AAT) visceral (VAT), subcutaneous (SAT), pancreatic, and hepatic adipose tissue) by MRI (N=92), and adiposity‐related factors of visceral fat (TNF‐α, Leptin), pancreases (PP, PYY), and liver (PAI‐1, Fetuin) via serum (N=26).ResultHigh pancreatic fat percentage was associated with lower hippocampal and IFG volumes, and lower executive memory function. High hepatic fat percentage was associated with lower hippocampal volume and lower executive memory function. High VAT percentage was associated with lower amygdalar and hippocampal volumes, while high VAT volume was associated with lower cognitive functioning (executive and working memory, language, and global cognition). Serum levels of PP, PAI‐1, and Fetuin were negatively associated with para‐hippocampal and IFG volumes. Serum levels of Leptin were associated with amygdala and hippocampal volumes. High levels of PYY, PAI‐1, and TNF‐α were associated with lower executive memory function.ConclusionGreater regional abdominal adiposity and related secreted factors are associated with poorer cognitive functions and lower volumes of cognition and BMI‐related brain regions, already in midlife in asymptomatic individuals enriched for AD risk, regardless of global body adiposity measured by BMI. These results strongly support our overall hypothesis that specific fat deposits in specific tissues and organs are differentially associated with cerebrovascular and AD‐related neuropathology and cognition, advancing the field to new potential mechanistic pathways underlying the adipose tissue‐brain link.

Abstract 11432: The Impact of Regional Adipose Tissue Deposition on Physical Activity in Heart Failure with Preserved Ejection Fraction

Introduction: Obesity is common in heart failure with preserved ejection fraction (HFpEF) and is directly linked with lower levels of physical activity (PA). Visceral adiposity (VAT) is more common in HFpEF than controls and may play a role in its pathogenesis, characterized by impaired exercise capacity (peak VO 2 ). The direct relationship between VAT and PA in HFpEF is unknown. Hypothesis: Compared to controls, HFpEF patients will have excess regional adiposity (VAT, subcutaneous (SAT), and intramuscular (IMAT)), and these fat depots will be associated with lower levels of chronic physical activity. Methods: HFpEF patients (n=51; age 70±9) and non-HFpEF controls (n=49; age 65±5) prospectively underwent body composition measurement by dual-energy x-ray absorptiometry and magnetic resonance imaging. Peak VO 2 was measured by standard cardiopulmonary exercise testing. PA was monitored continuously via accelerometry over two weeks. Data were binned in arbitrary accelerometry units, averaged and stored in 30-second epochs (counts per epoch, CPE). Models were adjusted for age, sex, and ideal body weight. Results: HFpEF were less active overall (3.15±0.80 vs 3.59±0.73 CPE), had less moderate intensity PA (10.13±0.04 vs 10.15±0.03 CPE), and less morning (3.83±1.15 vs 4.24±1.09 CPE) and afternoon (3.84± 1.20 vs 4.53± 0.97 CPE) (p<0.05 for all) PA. Patients with HFpEF spent a greater proportion of time sedentary (0.71±0.08 vs 0.67±0.08 CPE) and less time in moderate (0.04±0.03 vs 0.06±0.03 CPE) and vigorous (0.02±0.01 vs 0.03±0.03 CPE) PA (p<0.01 for all). Chronic PA was significantly associated with regional fat depots (VAT β= -0.003, 95% CI: -0.004-0.001; SAT β= -0.003, 95%CI: -0.004-0.001; IMAT β=-0.02, 95% CI: -0.04—0.01) as a combined cohort (p<0.01 for all). Muscle quality (β=0.28, 95%CI: 0.15-0.40), peak VO 2 (β=0.08, 95% CI: 0.03-0.13), and peak watts (β=0.01, 95% CI: -0.004-0.02) were associated with PA in HFpEF only (p≤0.01 for all). Conclusions: The amount and pattern of PA differs between HFpEF and controls, as do relationships between regional fat depots and PA, and the relationship of PA and peak VO 2 . Further investigation is needed to better understand the temporality and mechanisms related to the pathophysiology and severity of HFpEF.

Abstract 10538: Differences in Oxygen Uptake Kinetics Across Ejection Fraction Phenotypes in Heart Failure

Introduction: Peripheral factors contribute to exercise limitations in heart failure (HF) with preserved ejection fraction (HFpEF) and may be related to excess regional adiposity. Slowed oxygen uptake (VO 2 ) kinetics are common in HF with reduced ejection fraction (HFrEF) and reflect peripheral O 2 transport impairments and abnormal muscle metabolic control. Differences in VO 2 kinetics between HFpEF and HFrEF may reveal phenotype-specific impairments in peripheral O 2 transport but remain unknown. Hypothesis: We hypothesized that VO 2 kinetics are slower in HFpEF (compared to HFrEF) and associated with greater leg adiposity. Methods: Patients with HFpEF (n=12; 3 women; 66±6 yrs; 29±3 kg/m 2 ; ejection fraction: 59±5%), HFrEF (n=12; 3 women; 62±9 yrs; 28±4 kg/m 2 ; ejection fraction: 37±8%), and controls (n=12; 3 women; 65±5 yrs; 28±3 kg/m 2 ) cycled at 20 W for 5 minutes prior to a maximal exercise test to determine VO 2peak . Age, sex, and BMI were matched by design and were not different among groups (p>0.05). A monoexponential function with a time delay was used to describe the VO 2 transition from rest to 20 W and calculate the O 2 deficit. Leg fat mass was measured via dual energy X-ray absorptiometry. Results: VO 2peak was lower in HFpEF (18.6±6.2 mL/kg/min) and HFrEF (19.0±3.7 mL/kg/min) compared to controls (26.0±3.1; both p<0.05). Amplitude (HFpEF: 507±97 mL/min; HFrEF: 443±91 mL/min; controls: 477±117 mL/min) and time delay (HFpEF: 16±9 s; HFrEF: 11±7 s; controls: 11±6 s) were not different among groups (p>0.05). The time constant was slower in HFrEF compared to controls (45±9 s vs. 32±6 s; p=0.03) and further slowed in HFpEF (66±18 s; p<0.001). The O 2 deficit was significantly greater in HFpEF (895±201 mL) and HFrEF (649±131 mL) compared to controls (590±125 mL; both p<0.05). There were no differences in percent leg fat mass among groups (HFpEF: 33±8%; HFrEF: 31±6%; controls: 34±9%) and no associations were detected between percent leg fat mass and any VO 2 parameters (all p>0.05). Conclusions: Patients with HFpEF exhibited slower VO 2 kinetics compared to HFrEF with no association to leg adiposity. These data suggest differences in peripheral O 2 transport and intramuscular metabolic control abnormalities between HF phenotypes.

Sex-specific associations of body composition measures with cardiac function and structure after 8\xa0years of follow-up

We investigated the prospective associations of body composition with cardiac structure and function and explored effect modification by sex and whether inflammation was a mediator in these associations. Total body (BF), trunk (TF) and leg fat (LF), and total lean mass (LM) were measured at baseline by a whole body DXA scan. Inflammatory biomarkers and echocardiographic measures were determined both at baseline and follow-up in the Hoorn Study (n = 321). We performed linear regression analyses with body composition measures as determinant and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) or left atrial volume index (LAVI) at follow-up as outcome. Additionally, we performed mediation analysis using inflammation at follow-up as mediator. The study population was 67.7 ± 5.2 years and 50% were female. After adjustment, BF, TF and LF, and LM were associated with LVMI with regression coefficients of 2.9 (0.8; 5.1)g/m2.7, 2.3 (0.6; 4.0)g/m2.7, 2.0 (0.04; 4.0)g/m2.7 and − 2.9 (− 5.1; − 0.7)g/m2.7. Body composition measures were not associated with LVEF or LAVI. These associations were not modified by sex or mediated by inflammation. Body composition could play a role in the pathophysiology of LV hypertrophy. Future research should focus on sex differences in regional adiposity in relation with diastolic dysfunction.

Adults with Crohn\u2019s disease exhibit elevated gynoid fat and reduced android fat irrespective of disease relapse or remission

Crohn’s disease (CD) is a debilitating inflammatory bowel condition of unknown aetiology that is growing in prevalence globally. Large-scale studies have determined associations between female obesity or low body mass index (BMI) with risk of CD at all ages or 8– < 40 years, respectively. For males, low BMI entering adult life is associated with increased incidence of CD or ulcerative colitis up to 40 years later. Body composition analysis has shown that combinations of lean tissue loss and high visceral fat predict poor CD outcomes. Here, we assessed dietary intake, physical activity and whole or regional body composition of patients with CD relapse or remission. This anthropometric approach found people with CD, irrespective of relapse or remission, differed from a large representative healthy population sample in exhibiting elevated gynoid fat and reduced android fat. CD is associated with mesenteric adipose tissue, or “creeping fat”, that envelops affected intestine exclusive of other tissue; that fat is localised to the android region of the body. In this context, CD mesenteric adiposity represents a stark juxtaposition of organ-specific and regional adiposity. Although our study population was relatively small, we suggest tentatively that there is a rationale to refer to Crohn’s disease as a fatty intestine condition, akin to fatty liver conditions. We suggest that our data provide early insight into a subject that potentially warrants further investigation across a larger patient cohort.

Genetic underpinnings of regional adiposity distribution in African Americans: Assessments from the Jackson Heart Study.

African ancestry individuals with comparable overall anthropometric measures to Europeans have lower abdominal adiposity. To explore the genetic underpinning of different adiposity patterns, we investigated whether genetic risk scores for well-studied adiposity phenotypes like body mass index (BMI) and waist circumference (WC) also predict other, less commonly measured adiposity measures in 2420 African American individuals from the Jackson Heart Study. Polygenic risk scores (PRS) were calculated using GWAS-significant variants extracted from published studies mostly representing European ancestry populations for BMI, waist-hip ratio (WHR) adjusted for BMI (WHRBMIadj), waist circumference adjusted for BMI (WCBMIadj), and body fat percentage (BF%). Associations between each PRS and adiposity measures including BF%, subcutaneous adiposity tissue (SAT), visceral adiposity tissue (VAT) and VAT:SAT ratio (VSR) were examined using multivariable linear regression, with or without BMI adjustment. In non-BMI adjusted models, all phenotype-PRS were found to be positive predictors of BF%, SAT and VAT. WHR-PRS was a positive predictor of VSR, but BF% and BMI-PRS were negative predictors of VSR. After adjusting for BMI, WHR-PRS remained a positive predictor of BF%, VAT and VSR but not SAT. WC-PRS was a positive predictor of SAT and VAT; BF%-PRS was a positive predictor of BF% and SAT only. These analyses suggest that genetically driven increases in BF% strongly associate with subcutaneous rather than visceral adiposity and BF% is strongly associated with BMI but not central adiposity-associated genetic variants. How common genetic variants may contribute to observed differences in adiposity patterns between African and European ancestry individuals requires further study.

Distinct opposing associations of upper and lower body fat depots with metabolic and cardiovascular disease risk markers.

To examine the associations of total and regional adiposity with metabolic and cardiovascular disease (CVD) risk markers. This cross-sectional study included 1080 (53.8% men, aged 39-44 years) individuals from South India. Anthropometry (height, weight, waist and hip circumference), body composition assessment using dual-energy X-ray absorptiometry (DXA), blood pressure (BP), and plasma glucose, insulin and lipids were measured. Regression analysis was used to examine associations of standardized fat measurements with type 2 diabetes (T2D), insulin resistance (IR), hypertension and hypertriglyceridemia and continuous measurements of BP, glucose, insulin, HOMA-IR and lipids. Contour plots were constructed to visualize the differential effect of upper and lower fat depots. DXA-measured fat depots were positively associated with metabolic and CVD risk markers. After adjusting for fat mass index, upper body fat remained positively, while lower body fat was negatively associated with risk markers. A one standard deviation (SD) increase in android fat showed higher odds ratios (ORs) for T2D (6.59; 95% CI 3.17, 13.70), IR (4.68; 95% CI 2.31, 9.50), hypertension (2.57; 95% CI 1.56, 4.25) and hypertriglyceridemia (6.39; 95% CI 3.46, 11.90) in men. A 1 SD increase in leg fat showed a protective effect with ORs for T2D (0.42; 95% CI 0.24, 0.74), IR (0.31; 95% CI 0.17, 0.57) and hypertriglyceridemia (0.61; 95% CI 0.38, 0.98). The magnitude of the effect was greater with DXA-measured fat compared with anthropometry. At any level of total body fat, upper and lower body fat depots demonstrate opposite risk associations with metabolic and CVD risk markers in Asian Indians.

Pericardial Adipose Tissue Volume and Left Ventricular Assist Device-Associated Outcomes

Pericardial adipose tissue (PAT) is associated with adverse cardiovascular outcomes in those with and without established heart failure (HF). However, it is not known whether PAT is associated with adverse outcomes in patients with end-stage HF undergoing left ventricular assist device (LVAD) implantation. This study aimed to evaluate the associations between PAT and LVAD-associated outcomes. We retrospectively measured computed tomography-derived PAT volumes in 77 consecutive adults who had available chest CT imaging prior to HeartMate 3 LVAD surgery between October 2015 and March 2019 at Duke University Hospital. Study groups were divided into above-median (≥219 cm3) and below-median (<219 cm3) PAT volume. Those with above-median PAT had a higher proportion of atrial fibrillation, chronic kidney disease and ischemic cardiomyopathy. Groups with above-median vs below-median PAT had similar Kaplan-Meier incidence rates over 2 years for (1) composite all-cause mortality, redo-LVAD surgery and cardiac transplantation (35.9 vs 32.2%; log-rank P = 0.65) and (2) composite incident hospitalizations for HF, gastrointestinal bleeding, LVAD-related infection, and stroke (61.5 vs 60.5%; log-rank P = 0.67). In patients with end-stage HF undergoing LVAD therapy, PAT is not associated with worse 2-year LVAD-related outcomes. The significance of regional adiposity vs obesity in LVAD patients warrants further investigation.

Regional Adiposity and Risk of Heart Failure and Mortality: The Jackson Heart Study.

BackgroundVisceral adipose tissue (VAT) is associated with incident heart failure (HF) and HF with preserved ejection fraction, yet it is unknown how pericardial and abdominal adiposity affect HF and mortality risks in Black individuals. We examined the associations of pericardial adipose tissue (PAT), VAT, and subcutaneous adipose tissue (SAT) with incident HF hospitalization and all‐cause mortality in a large community cohort of Black participants.Methods and ResultsAmong the 2882 Jackson Heart Study Exam 2 participants without prevalent HF who underwent body computed tomography, we used Cox proportional hazards models to examine associations between computed tomography–derived regional adiposity and incident HF hospitalization and all‐cause mortality. Fully adjusted models included demographics and cardiovascular disease risk factors. Median follow‐up was 10.6 years among participants with available VAT (n=2844), SAT (n=2843), and PAT (n=1386). Fully adjusted hazard ratios (95% CIs) of distinct computed tomography–derived adiposity measures (PAT per 10 cm3, VAT or SAT per 100 cm3) were as follows: for incident HF, PAT 1.08 (95% CI, 1.02–1.14) and VAT 1.04 (95% CI, 1.01–1.08); for HF with preserved ejection fraction, PAT 1.13 (95% CI, 1.04–1.21) and VAT 1.07 (95% CI, 1.01–1.13); for mortality, PAT 1.07 (95% CI, 1.03–1.12) and VAT 1.01 (95% CI, 0.98–1.04). SAT was not associated with either outcome.ConclusionsHigh PAT and VAT, but not SAT, were associated with incident HF and HF with preserved ejection fraction, and only PAT was associated with mortality in the fully adjusted models in a longitudinal community cohort of Black participants. Future studies may help understand whether changes in regional adiposity improves HF, particularly HF with preserved ejection fraction, risk predictions.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT00005485.

Brown adipose tissue is associated with healthier body fat distribution and metabolic benefits independent of regional adiposity

SummaryThe association of brown adipose tissue (BAT) and body fat distribution and their combined effects on metabolic health in humans remains unknown. Here, we retrospectively identify individuals with and without BAT on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and assemble a propensity score-matched study cohort to compare body fat distribution and determine its role in mediating the benefits of brown fat. We find that BAT is associated with lower amounts of visceral adipose tissue and higher amounts of subcutaneous adipose tissue, resulting in less central obesity. In addition, BAT is independently associated with lower blood glucose and white blood cell count, improved lipids, lower prevalence of type 2 diabetes mellitus, and decreased liver fat accumulation. These observations are most prominent in individuals with central obesity. Our results support a role of BAT in protection from visceral adiposity and improved metabolic health.

Hyperinsulinemic Compensation for Insulin Resistance Occurs Independent of Elevated Glycemia in Male Dogs.

Insulin resistance engenders a compensatory increase in plasma insulin. Inadequate compensation is a primary element in the pathogenesis of type 2 diabetes. The signal that heralds developing insulin resistance and initiates hyperinsulinemic compensation is not known. It has often been assumed to be increased glucose. We tested this assumption by determining whether development of fasting and/or glucose-stimulated hyperinsulinemia with diet-induced insulin resistance occurs because of concomitant elevation of glycemia. Male dogs (n = 58) were fed a hypercaloric, fat-supplemented diet for 6 weeks. Dogs underwent magnetic resonance imaging to quantify total and regional (visceral, subcutaneous) adiposity as well as euglycemic hyperinsulinemic clamps. A subset of animals also underwent an insulin-modified intravenous glucose tolerance test to assess insulin sensitivity, acute insulin response (AIRg), and glucose effectiveness. Fat feeding caused modest weight gain, increased visceral and subcutaneous fat, and insulin resistance at both peripheral and hepatic levels. Hyperinsulinemic compensation was observed in fasting levels as well as increased AIRg. However, we observed absolutely no increase in carefully measured fasting, evening (6 to 8 pm) or nocturnal glycemia (2 to 4 am). Insulin resistance and hyperinsulinemia occurred despite no elevation in 24-hour glucose. Compensatory development of hyperinsulinemia during diet-induced insulin resistance occurs without elevated fasting or 24-hour glycemia. These data refute the idea that glucose itself is a requisite signal for β-cell upregulation. Alternative feedback mechanisms need to be identified.

Relative Fat Mass (RFM) as an Estimate of Total Adiposity in Older Adults

Abstract Objectives It is imperative to accurately estimate whole body fat percentage (%fat) in order to understand the deleterious nature of excess adiposity on cardiometabolic disease risk. However, cost and accessibility often preclude the use of advanced assessment methods. Relative fat mass (RFM), an emerging estimator of whole body %fat based upon waist circumference, height, and biological sex, has yet to be evaluated in an older adult population. The purpose of this study was to examine the relationship between RFM and gold standard measures of adiposity among older adults, and to evaluate whether changes in RFM reflected changes in %fat following a 12-month lifestyle intervention. Methods This study was ancillary to a randomized controlled trial investigating the effects of a lifestyle intervention with and without intentional energy restriction. (Clinicaltrials.gov #NCT00955903). Older adults with obesity (N = 163, 37.4% male, 70.3 ± 4.7 years) were randomized to one of three groups: exercise only, exercise + nutrient-dense weight maintenance diet, or exercise + nutrient-dense energy restriction of 500 kcal/d. Total and regional adiposity were determined by dual-energy X-ray absorptiometry (DXA) at baseline and 12 months. Data were analyzed using Spearman's correlations, Wilcoxon, Kruskal-Wallis, and linear regression tests. Results At baseline, significant correlations were observed between RFM and DXA whole body %fat (r = 0.751, P &amp;lt; 0.001), DXA total fat (r = 0.353, P &amp;lt; 0.001), and DXA trunk %fat (r = 0.661, P &amp;lt; 0.001). Additionally, RFM was a significant predictor of DXA whole body %fat (P &amp;lt; 0.001) and accounted for 63.5% of model variance. From baseline to 12 months, a significant reduction in RFM was observed among participants in the exercise only and exercise + energy restriction groups (P = 0.020, P &amp;lt; 0.001, respectively). Magnitude of RFM change did not differ among groups. Notably, changes in RFM were significantly correlated with changes in DXA whole body %fat (r = 0.279, P = 0.001) and DXA trunk %fat (r = 0.276, P = 0.001). Conclusions Results support use of RFM as an estimate of whole body %fat, as well as an indicator of its sensitivity to change in fat mass over 12 months in older adults. Incorporation of RFM in cardiometabolic research may provide meaningful information not reflected in conventional body composition measures such as body mass index. Funding Sources NIH

Abstract P131: Changes In Bile Acid Subtypes And Improvements In Adiposity And Energy Metabolism In Response To Weight-loss Diets

Introduction: Bile acids (BAs) are synthesized in the liver from cholesterol, and gut microbiota transform the host-derived primary BAs into secondary BAs in the intestine. Emerging evidence suggests that different types of circulating BAs may play pivotal roles in regulating energy metabolism and body adiposity. Hypothesis: We comprehensively examined whether changes in different BA subtypes after consuming weight-loss diets were associated with improvements in energy metabolism and body adiposity among patients with obesity. Methods: This study included 551 overweight and obese adults who participated in a 2-year weight-loss dietary intervention, the POUNDS Lost trial. Blood levels of 14 types of BAs (primary and secondary unconjugated BAs and their taurine-/glycine-conjugates) were measured at baseline and 6 months after the intervention; changes in BAs from baseline to 6 months after the intervention were calculated. We evaluated changes in resting energy expenditure, weight, and waist circumference. Also, body composition was assessed by the dual-energy X-ray absorptiometry (DEXA) scans, and fat distribution was assessed by computed tomography (CT) scans. Results: At baseline, higher primary and secondary BAs were related to greater degrees of adiposity and energy expenditure. At 6 months after the intervention, greater decreases in primary BAs (cholic acid [CA] and chenodeoxycholic acid) and secondary BAs (deoxycholic acid [DCA] and lithocholic acid [LCA]) and their conjugated subtypes (except for glycolithocholic acid) were significantly associated with more decreases in weight and waist circumference at 6 months after the intervention (P values after controlling for the multiple testing, P FDR &lt;0.05). Greater reductions in the primary BAs (both unconjugated and conjugated types) and secondary BAs (DCA and its taurine-/glycine-conjugated forms) were also significantly ( P FDR &lt;0.05) associated with more decreases in resting energy expenditure at 6 months. We found that reductions in two BA subtypes, glycocholic acid (GCA) and glycoursodeoxycholic acid (GUDCA), were consistently and significantly associated with improvements in energy metabolism, general and central adiposity, as well as body fat composition and visceral adipose tissue mass. Further, the initial (6-month) changes in several primary and secondary BAs (including GCA and GUDCA) were significantly predictive of the long-term successful weight loss (weight loss of more than 5% loss from the initial weight) at 2 years. Conclusions: Weight-loss diet-induced changes in circulating various BAs may be involved in improving general and central adiposity and energy metabolism. Changes in specific BA subtypes would be potential targets for improving regional adiposity and achieving successful weight-loss among patients with obesity.

Adiponectin is associated with insulin sensitivity in white European men but not black African men.

We aimed to assess ethnic differences in inflammatory markers and their relationships with insulin sensitivity and regional adiposity between white European and black African men. A total of 53 white European and 53 black African men underwent assessment of inflammatory markers alongside Dixon-magnetic resonance imaging to quantify subcutaneous and visceral adipose tissue and intrahepatic lipid. A hyperinsulinaemic-euglycaemic clamp was used to measure whole-body and adipose tissue insulin sensitivity. To assess ethnic differences in relationships, the statistical significance of an interaction term between adipokines and ethnic group was tested in multivariable regression models. The black African men exhibited significantly lower adiponectin and tumour necrosis factor-α (TNF-α) and greater interleukin-10 (IL-10) compared to white European men (all p<0.05). There were no statistically significant ethnic differences in leptin, resistin, IL-6, interferon-γ, IL-13, IL-1β, IL-8 and vascular endothelial growth factor. Several relationships differed significantly by ethnicity such that they were stronger in white European than black African men including IL-6 with visceral adipose tissue; adiponectin with subcutaneous adipose tissue; leptin with intrahepatic lipid; adiponectin, IL-6 and TNF-α with whole-body insulin sensitivity and TNF-α with adipose tissue insulin sensitivity (all pinteraction<0.05). Leptin significantly predicted whole-body insulin sensitivity in white European (R2 =0.51) and black African (R2 =0.29) men; however, adiponectin was a statistically significant predictor in only white European men (R2 =0.22). While adiponectin is lower in black African men, its insulin sensitising effects may be greater in white men suggesting that the role of adipokines in the development of type 2 diabetes may differ by ethnicity.

Distinct metabolite profiles of adiposity indices and their relationships with habitual diet in young adults

Background and aimsObesity is characterized as overall or regional adiposity accumulation. However, the metabolic status underlying fat accumulation was not well understood. We sought to identify metabolite profiles based on their correlations with body mass index (BMI), body fat percentage (BFP), waist circumference (WC), and visceral adiposity index (VAI) in young Chinese adults (19–37 years old), and their associations with dietary consumption were also explored. Methods and resultsA total of 86 plasma samples were analyzed using untargeted lipidomics and metabolomics approaches. Metabolite profiles of adiposity indices were identified using random forest modelling. Ridge regression was used to generate metabolite scores. Overall, 30, 46, 30, and 20 metabolites correlated with BMI, BFP, WC, and VAI, respectively, which resulted in metabolite scores for each index. Top three enriched categories of the identified metabolites were glycerophospholipids, glycerolipids, and sphingolipids, with some specific metabolites (such as phosphatidylserine (37:2), phatidylethanolamine (42:4), and ceramide (40:0)) exclusively associated with overall adiposity, and some other metabolites exclusively associated with abdominal adiposity indices, e.g., triradylglycerol (45:0, 52:4, and 35:0) and diacylglycerol (38:4, 36:3, and 36:5). Moreover, metabolite scores were negatively associated with the intake of food rich in protein or fiber, while they were positively associated with food rich in carbohydrate, with similar results for adiposity indices. ConclusionWe observed unique metabolite profiles of regional or overall fat deposition in young adults. Glycerophospholipids, glycerolipids, or sphingolipids may be involved in the regulation of adiposity accumulation, affected by dietary exposures.

Body Composition Methods in Adults with Type 2 Diabetes or at Risk for T2D: a Clinical Review.

The aim of this study is to summarize anthropometric and advanced methods used to assess body composition in adults diagnosed with type 2 diabetes (T2D) or at risk for T2D that provide clinically relevant information about T2D disease-related complications or risk factors. Anthropometry is commonly used in clinical settings; however, provides unreliable estimates of fat mass, fat-free mass, and body fat distribution for metabolic health assessments compared to advanced techniques such as bioelectrical impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA), computerized tomography (CT), and magnetic resonance imaging (MRI). Few studies report the clinical use of anthropometric and advanced body composition methods that identify T2D disease-related complications or T2D risk factors. Anthropometry, BIA, DXA, CT, and MRI were used to estimate body adiposity and distribution, visceral and subcutaneous adipose tissue depots, and skeletal muscle mass. Review findings indicate that these methods were capable of identifying clinically relevant T2D disease-related complications such as sarcopenia and T2D risk factors such as obesity or regional adiposity. However, estimates were often sex and race/ethnicity specific warranting cross-validation of these methods in broader populations with T2D or risk for T2D prior to clinical implementation.

Body composition and metabolic parameters in men with chronic traumatic paraplegia – A pilot study from India

Objective To study body composition, measures of insulin resistance and dyslipidemia in Indian men with paraplegia as compared to age and body mass index (BMI) matched able-bodied men. Design Cross sectional study Setting Departments of Physical Medicine and Rehabilitation and Endocrinology Participants Males aged 18–45 years with chronic traumatic paraplegia versus age and BMI-matched able-bodied men Interventions None Main outcome measures Measures of body composition such as total body fat, lean mass, regional adiposity using dual energy x-ray absorptiometry (DXA), metabolic profile and insulin resistance Results Subjects with paraplegia (n = 43), compared to controls (n = 36), had higher %Fat mass (FM) (25.5 (21.2–28.9) vs 20.2 (15.9–22.2); P < 0.01), lower trunk to leg ratio (0.66 (0.51–0.73) vs 0.87 (0.72–0.94); P < 0.01), lower lean mass index (14.38 (2.57) vs 17.80 (2.34); P < 0.01) and lower appendicular lean mass index (5.81 ± 1.26 vs 8.17 ± 1.12; P < 0.01). Fasting blood glucose (mg/dl) was higher (89.0(81.5–96.5) vs 80.0 (74.5–88.2); P < 0.01), Homeostasis model assessment of insulin resistance was higher (1.33 (1.03–2.12) vs 0.94 (0.52–1.78); P = 0.02), Quantitative insulin sensitivity check index (QUICKI) was lower (0.36 ± 0.04 vs 0.38 ± 0.05; P = 0.02) and HDL-C was lower (33.00 (30.00–42.75) vs 38.50 (33.00–43.25); P < 0.02) in cases compared to controls. QUICKI correlated positively with HDL-C and negatively with %FM, estimated VAT volume and TG. Trunk to leg ratio correlated positively with TG even after controlling for %FM. Conclusion Men with chronic paraplegia had lower lean mass, higher total and regional fat mass, increased insulin resistance and low HDL-C when compared with BMI-matched able-bodied controls. Both total and regional adiposity correlated with poor metabolic profile.