Adjustment For Total Fat Mass Research Articles

Fat Mass Accounts for Insulin Resistance Impact on Functional Decline and Mortality in Nondiabetic Older Adults

ObjectiveTo assess the potential role of body composition in the association of insulin resistance (IR) with functional decline and mortality in nondiabetic older persons. DesignLongitudinal population-based cohort of community-dwelling people from Toledo, Spain, aged 65 years or older. Setting and ParticipantsA total of 1114 nondiabetic persons from the Toledo Study of Healthy Aging cohort (mean age: 74.5, 56.10% female) with complete data at baseline were included. Only 914 participants had fully assessment of functional evaluation during the follow-up period. MethodsIR was determined by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was assessed by the Frailty Trait Scale-5 (FTS-5) at baseline and after 2.99 years’ median follow-up period. A total of 319 participants experienced functional decline (2.5-point reduction in the FTS-5 score). A total of 143 deaths were recorded (6.31 years median follow-up) from the Spanish National Death Index. Body compositions were determined using dual-energy x-ray absorptiometry. Multivariate regression models analyzed the effect of HOMA-IR on outcomes, with age, sex, Charlson index, and number of medications included in the basic adjustment model. ResultsA 1-logaritmic unit increment in HOMA-IR increased the risk of functional decline after basic adjustment [odds ratio (95% confidence interval): 1.41 (1.09–1.83), P = .009]. This significant association was lost when further adjusted for total fat mass [1.14 (0.86–1.50)] and trunk fat mass [1.03 (0.77–1.37)], which accounted for 62.92% and 91.49% of the association. HOMA-IR was inversely associated with mortality risk [hazard ratio 0.66 (0.49–0.87), P = .0037], an association lost after adjustment for total fat mass [0.74 (0.55–1.01)] and trunk fat mass [0.80 (0.58–1.09)], accounting for 29.05% and 45.78% of the association. Adjustment by lean mass did not modify any of the associations. Conclusions and ImplicationsBody fat mass, especially in the trunk region, mediates the association of IR with functional decline and to a lesser extent with reduced risk of mortality in nondiabetic older subjects.

HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution.

Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.

Abstract IA38: Racial/ethnic differences in liver fat, an obesity-associated risk factor for liver cancer

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is thought to be the main driver for the recent rise of chronic liver disease and liver cancer. NAFLD is also associated with other obesity-related metabolic diseases. Relative fat deposition in the liver varies by race/ethnicity and may partially account for liver cancer disparities. Thus, we aimed to compare liver fat content across five racial/ethnic groups, assess their contribution to the metabolic syndrome (MetSx), and predict NAFLD using common blood biomarkers. Methods: We conducted a cross-sectional study within the Multiethnic Cohort. A total of 1,861 healthy men and women aged 60-77 years were recruited, after stratification on sex, ethnicity (African, Japanese, Latino, Native Hawaiian, or white ancestry), and six BMI categories (range, 17.1-49.8 kg/m2). We estimated total fat mass using DXA and liver fat content using abdominal MR imaging. Fasting blood was analyzed for ~50 markers including adipocytokines, insulin and IGFs, lipids and lipid-soluble micronutrients, liver enzymes, and steroid hormones, using multiple assay platforms. Liver fat amounts were compared across sex and ethnic groups after adjustment for age, total fat mass, and height. The contribution of liver fat to MetSx was estimated in multivariable-adjusted mediation analysis. A prediction model for NAFLD was developed using regularized logistic regression. Results: The correlation between liver fat and total fat was only moderate (rSp = 0.34) and varied across ethnic groups (0.20-0.55). Liver fat content was similar between the sexes but differed by ethnicity (p<.0001), with a four-fold range in NAFLD prevalence between Japanese Americans (57% in men, 72% in women) and African Americans (12%, 19%) after adjustment for total fat mass. Total fat-adjusted prevalence of MetSx also differed by ethnicity: compared to whites, it was higher among Japanese Americans and Native Hawaiian women and lower among African Americans and Latinos. This ethnic difference was significantly mediated by liver fat among African Americans (proportion mediated =19-24%), Japanese Americans (22-34%), and Native Hawaiian women (20%). The final prediction model for NAFLD included age, sex, BMI, waist circumference, waist/hip, and top five biomarker predictors (IGFBP2, HOMA-IR, TG, adiponectin, SHBG). Discrimination of NAFLD cases in a validation dataset had high accuracy (AUC=0.90), across ethnic groups (AUCs of 0.80-0.96), and was significantly improved by the biomarkers (p's for contrast<.0001, except in African Americans). Conclusions: Relative fat storage in the liver varies substantially by race/ethnicity. In particular, Japanese Americans and Native Hawaiian women appear to experience a greater metabolic burden from their propensity to store excess fat in ectopic areas, which is consistent with a stronger association of BMI with liver cancer in these groups. Key metabolism markers may be used to successfully detect and monitor NAFLD patients of in various ethnic groups. Citation Format: Unhee Lim, Lynne R. Wilkens, Kristine R. Monroe, Iona Cheng, Bruce S. Kristal, Johanna W. Lampe, Meredith A. Hullar, John Shepherd, Thomas Ernst, Loic Le Marchand. Racial/ethnic differences in liver fat, an obesity-associated risk factor for liver cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA38.

Lean body mass and risk of incident atrial fibrillation in post-menopausal women.

High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31). Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF.

Sex Differences in the Relationship between C-Reactive Protein and Body Fat

C-reactive protein (CRP) levels are significantly influenced by adiposity and are higher in women compared with men. We postulated that there may be sex differences in the relationship between CRP and body fat. We measured CRP and body fat parameters in 1166 men and 1413 women ages 30-65 in the population-based Dallas Heart Study. Total fat mass (TFM) was measured using dual-energy x-ray absorptiometry scanning and was subdivided into truncal fat (TrF) and lower body fat (LBF). The TrF/LBF ratio was used to measure fat distribution. Abdominal fat compartments (ip and sc) were measured using magnetic resonance imaging. Log-transformed CRP was used as the outcome variable in sex-combined models with interaction tests. Median body mass index was higher in women than in men (29.9 vs. 28.2 kg/m(2)), as was TFM (29.7 vs. 20.5 kg) (P < 0.001 each). TFM was linearly associated with log CRP in both sexes, with a steeper slope of association in women (P interaction = 0.003). CRP increased to a greater degree with increasing TrF (P interaction = 0.0004) in women compared with men, even after adjustment for TFM; values were similar across sexes for LBF. Fat distribution (TrF/LBF ratio) was more strongly associated with CRP levels in women vs. men (R(2) adjusted for TFM = 0.04 vs. 0.008). Greater increases in CRP were also observed with increasing ip and sc fat in women compared with men. The quantity and distribution of body fat influence CRP to a greater extent in women compared with men. Adiposity as a contributor to subclinical inflammation may be particularly relevant in women.

Accuracy of Predictive Equations for Basal Metabolic Rate and Contribution of Abdominal Fat Distribution to Basal Metabolic Rate in Obese Japanese People

BACKGROUND: Large errors may occur when predicting basal metabolic rate (BMR) based on physical characteristics in obese people. In addition, the contribution of abdominal visceral fat to BMR remains controversial. This study examined the accuracy of several predictive equations for BMR and the contribution of abdominal fat distribution to BMR in obese Japanese participants in the Saku Control Obesity Program (SCOP). METHODS: BMR was determined using a mask and Douglas bag in adult males (n = 12) and females (n = 11). We measured abdominal subcutaneous and visceral fat areas using computerized tomography.RESULTS: All the equations, with the exception of Bernstein’s, overestimated BMR in obese males. Some equations, including the Japan-Dietary Reference Intakes and the Food and Agriculture Organization of the United Nations/World Health Organization/United Nations University (FAO/WHO/UNU) equations, overestimated BMR in obese females, while the Harris-Benedict and Henry equations provided relatively accurate predictions of BMR in obese females. We found no correlation between abdominal visceral fat area and BMR when adjusted for sex, fat-free mass, and abdominal subcutaneous fat area (partial r =−0.022). Abdominal subcutaneous fat area correlated significantly with BMR when adjusted for sex, fat-free mass, and abdominal visceral fat area (partial r = 0.732), although this correlation was no longer significant after adjustment for total fat mass (partial r = 0.266).CONCLUSIONS: In obese Japanese subjects, most the predictive equations overestimated BMR in males, whereas some equations were relatively accurate for females. Our findings indicate abdominal fat distribution may not be independently related with BMR.

Relationship between Visceral Fat and PAI-1 in Overweight Men and Women before and after Weight Loss

This study was aimed at evaluating the relationship between visceral fat accumulation and plasma plasminogen activator inhibitor-1 (PAI-1) levels in healthy, obese men and women undergoing weight loss therapy. The subjects, 25 men and 25 premenopausal women, aged between 26 and 49 years, with an initial body mass index between 28 and 38 kg/m2, received a controlled diet for 13 weeks providing a 4.2 MJ/day energy deficit. Magnetic resonance imaging was used to measure visceral and subcutaneous abdominal fat. Our results show that before weight loss visceral fat was significantly correlated with PAI-1 in men (r = 0.45; p<0.05), but not in women (r = -0.15; ns). The association between visceral fat and PAI-1 in men remained significant after adjustment for age and total fat mass, and multiple linear regression analysis showed a significant independent contribution of visceral fat to plasma PAI-1 levels. Both visceral fat areas and PAI-1 levels decreased significantly with weight loss in both men and women. Changes in visceral fat area were related to changes in PAI-1 in women (r = -0.43; p = 0.05) but not in men (r = -0.01; ns); however, this association in women disappeared after adjustment for total fat mass. We conclude that there is a relationship between visceral fat and PAI-1 in obese men but not in obese women, and that PAI-1 levels decrease substantially (52%) by weight loss, but this change is not related to changes in visceral fat mass per se.

Genetics of abdominal visceral fat levels

The purpose of this review is to explore the evidence accumulated thus far that suggests a genetic component to the observed variation in abdominal visceral fat (AVF) levels. The precise determination of AVF levels in humans is limited to methods such as computerized tomography and magnetic resonance imaging; thus, few studies have examined the role of genetic factors on this phenotype. Evidence from the Québec Family Study (QFS) and the HERITAGE Family Study indicates that between 50–55% of the variance in AVF levels, adjusted for total fatness, is attributable to genetic factors. Additionally, a major gene hypothesis for AVF was supported in the both the QFS and HERITAGE Family Study. However, after adjustment for total fat mass the support for a major gene was reduced, suggesting that a major gene which affects fat mass may also affect AVF either directly (pleiotropy), or indirectly. The search for candidate genes that may impact AVF levels is in its infancy, and few candidate genes have been identified. However, the glucocorticoid receptor (GRL), ß3 adrenergic receptor (ADRB3), and fatty acid binding protein 2 (FABP2) genes have been significantly associated with AVF or intra-abdominal fat levels in humans. In addition, three quantitative trait loci obtained from crosses of mice, the Do2, Mob4, and Qbw1 loci have been linked with mesenteric or abdominal fat and are thus considered positional candidate genes for AVF levels. The search for candidate genes or random genetic markers associated with AVF levels is a challenging prospect. However, given the significant heritability of this phenotype, the quest remains promising. Am. J. Hum. Biol. 11:225–235, 1999. © 1999 Wiley-Liss, Inc.

Genetics of abdominal visceral fat levels.

The purpose of this review is to explore the evidence accumulated thus far that suggests a genetic component to the observed variation in abdominal visceral fat (AVF) levels. The precise determination of AVF levels in humans is limited to methods such as computerized tomography and magnetic resonance imaging; thus, few studies have examined the role of genetic factors on this phenotype. Evidence from the Québec Family Study (QFS) and the HERITAGE Family Study indicates that between 50-55% of the variance in AVF levels, adjusted for total fatness, is attributable to genetic factors. Additionally, a major gene hypothesis for AVF was supported in the both the QFS and HERITAGE Family Study. However, after adjustment for total fat mass the support for a major gene was reduced, suggesting that a major gene which affects fat mass may also affect AVF either directly (pleiotropy), or indirectly. The search for candidate genes that may impact AVF levels is in its infancy, and few candidate genes have been identified. However, the glucocorticoid receptor (GRL), ss3 adrenergic receptor (ADRB3), and fatty acid binding protein 2 (FABP2) genes have been significantly associated with AVF or intra-abdominal fat levels in humans. In addition, three quantitative trait loci obtained from crosses of mice, the Do2, Mob4, and Qbw1 loci have been linked with mesenteric or abdominal fat and are thus considered positional candidate genes for AVF levels. The search for candidate genes or random genetic markers associated with AVF levels is a challenging prospect. However, given the significant heritability of this phenotype, the quest remains promising. Am. J. Hum. Biol. 11:225-235, 1999. Copyright 1999 Wiley-Liss, Inc.

Familial clustering of insulin and abdominal visceral fat: the HERITAGE Family Study.

Abdominal visceral fat (AVF) is an obesity-related phenotype thought to be associated with insulin resistance, diabetes mellitus, and atherosclerosis. Significant genetic influences on both AVF and insulin levels have been reported. However, information is lacking as to whether common genetic influences on AVF and insulin levels exist. AVF was assessed by computed tomography scan, and fasting insulin was measured by RIA in 512 members of 98 sedentary Caucasian families participating in the HERITAGE Family Study. Baseline data, collected before exercise training, were used in the present investigation. A bivariate familial correlation model was applied to evaluate whether there are familial influences that are common to insulin and AVF before and after adjustment for total fat mass (FM), and to assess the overall heritability of insulin and AVF. The maximal heritability for AVF, before and after adjustment for total FM, was 42% and 50%, respectively; and for insulin, it was 21%. Interestingly, 29% of the familial influences on insulin were also common to AVF, whereas 14% of the familial influences on AVF were shared by insulin. Furthermore, after AVF was adjusted for total FM, these common familial influences were increased to 48% and 20%. Genes and/or familial nongenetic factors with pleiotropic effects seem to influence both AVF and plasma insulin levels to a certain degree. Genes involved in the regulation of lipid storage and mobilization in the abdominal fat depot are potential candidates for these genetic pleiotropic effects.

Effects of ethnicity, gender, obesity, and age on central fat distribution: Comparison of dual x-ray absorptiometry measurements in white, black, and Puerto Rican adults.

Population based studies relying primarily upon anthropometric surrogates of fat distribution have shown that central or upper-body adiposity is related to ethnicity, gender, age, and total body fatness. As an improvement over anthropometry, dual x-ray absorptiometry (DXA) provides more precise measurements of fat mass (FM) in the total body and trunk. DXA was performed on 510 apparently healthy White (81 females (f), 64 males (m)), Black (94 f, 79 m), and Puerto Rican (102 f, 100 m) adults aged 20-75 years in order to determine and compare the effects of race, gender, age, and total FM on trunk FM. Trunk FM was greater for Blacks and Puerto Ricans than Whites, irrespective of gender (P < 0.014). Puerto Rican males and females had a greater proportion of fat in the trunk (%TrFM) than Whites or Blacks (P < 0.001), and Whites and Blacks were similar with respect to %TrFM (P > 0.67). Females had less %TrFM than males in all three ethnic groups (all P < 0.001). Based on multiple regression analysis, ethnicity did not affect the relationship of trunk and total FM among males (P > 0.16), but the coefficient for total FM was larger for Puerto Rican compared to Black females (P = 0.043). Trunk FM increased with age in Whites and Puerto Ricans (P < 0.02), but not Blacks (P > 0.24). The effects of age did not differ by gender or ethnicity among Whites and Puerto Ricans (P > 0.10). Adjustment for total FM and age eliminated ethnic and gender differences in trunk FM (all P > 0.37). The results suggest that the high levels of central adiposity observed among Blacks and Hispanics relative to Whites reflect patterns of generalized obesity observed in the respective populations. Patterns of accumulation of truncal FM with increasing age and obesity may not be generalizable to all ethnic groups. Am. J. Hum. Biol. 10:361-369, 1998. © 1998 Wiley-Liss, Inc.

Effects of ethnicity, gender, obesity, and age on central fat distribution: Comparison of dual x‐ray absorptiometry measurements in white, black, and Puerto Rican adults

Population based studies relying primarily upon anthropometric surrogates of fat distribution have shown that central or upper-body adiposity is related to ethnicity, gender, age, and total body fatness. As an improvement over anthropometry, dual x-ray absorptiometry (DXA) provides more precise measurements of fat mass (FM) in the total body and trunk. DXA was performed on 510 apparently healthy White (81 females (f), 64 males (m)), Black (94 f, 79 m), and Puerto Rican (102 f, 100 m) adults aged 20–75 years in order to determine and compare the effects of race, gender, age, and total FM on trunk FM. Trunk FM was greater for Blacks and Puerto Ricans than Whites, irrespective of gender (P < 0.014). Puerto Rican males and females had a greater proportion of fat in the trunk (%TrFM) than Whites or Blacks (P < 0.001), and Whites and Blacks were similar with respect to %TrFM (P > 0.67). Females had less %TrFM than males in all three ethnic groups (all P < 0.001). Based on multiple regression analysis, ethnicity did not affect the relationship of trunk and total FM among males (P > 0.16), but the coefficient for total FM was larger for Puerto Rican compared to Black females (P = 0.043). Trunk FM increased with age in Whites and Puerto Ricans (P < 0.02), but not Blacks (P > 0.24). The effects of age did not differ by gender or ethnicity among Whites and Puerto Ricans (P > 0.10). Adjustment for total FM and age eliminated ethnic and gender differences in trunk FM (all P > 0.37). The results suggest that the high levels of central adiposity observed among Blacks and Hispanics relative to Whites reflect patterns of generalized obesity observed in the respective populations. Patterns of accumulation of truncal FM with increasing age and obesity may not be generalizable to all ethnic groups. Am. J. Hum. Biol. 10:361–369, 1998. © 1998 Wiley-Liss, Inc.