Liver Fat Content and Body Fat Distribution in Youths with Excess Adiposity.
ABSTRACT: This study had two main objectives: To examine the association between body fat distribution and non-alcoholic fatty liver disease (NAFLD) and liver fat content, and to determine whether the relationship between NAFLD and regional body fat distribution, with respect to liver fat content in youths with excess adiposity, is independent of cardiorespiratory fitness (CRF) and a healthy diet. Liver fat content (controlled attenuation parameter (CAP)), body fat distribution (body mass index (BMI) z-score, waist circumference, waist-to-height ratio, fat mass/height, body fat percentage, total fat mass, android-to-gynoid fat mass ratio, visceral adipose tissue (VAT), and lean mass index, determined by dual-energy X-ray absorptiometry (DXA)), CRF (20-m shuttle-run test), and healthy diet (adherence to the Mediterranean diet by KIDMED questionnaire) were measured in 126 adolescents (66% girls) aged between 11 and 17 years. Participants were assigned to two groups according to the presence or absence of hepatic steatosis (CAP values ?225 dB/m or <225 dB/m of liver fat, respectively). Considering the similar total fat values for the two groups (>30% by DXA), youths with NAFLD had higher fat distribution parameters than those without NAFLD, regardless of sex, age, puberty stage, lean mass index, CRF, and healthy diet (p < 0.01). In the non-NAFLD group, the association between hepatic fat and fat distribution parameters presented a similar pattern, although the association was statistically insignificant after adjusting for a potential confounding variable (ps > 0.05), except for the case of VAT. Body fat distribution parameters were higher in youths with NAFLD compared to those without NAFLD. Additionally, body fat distribution showed a significant association with liver fat content as assessed by CAP in youths with NAFLD independent of CRF and adherence to the Mediterranean diet, supporting the notion that upper body fat distribution might play a pivotal role in the development of NAFLD in adolescents. These results may have implications for the clinical management of youths with excess adiposity given the high prevalence of NAFLD in children and young adults.
Project description:Background: Recent studies in adult non-elderly and elderly individuals have reported a link between nonalcoholic fatty liver disease (NAFLD) and sarcopenia. Nonetheless, whether this relationship would be found outside these populations it is still unknown. Hence, we evaluated the relationship between NAFLD and skeletal muscle mass in children and adolescents with overweight/obesity. Methods: Two-hundred and thirty-four overweight/obese youths were enrolled. NAFLD was diagnosed by ultrasononography, after exclusion of infectious and metabolic disorders. Forty of the patients with NAFLD had also liver biopsy. Total and regional lean body mass and total fat mass measurements were obtained by dual-energy X-ray absorptiometry. The relative muscle mass (RMM) was defined as the percent of muscle mass (kg) relative to the sum of muscle and fat (kg) mass. Appendicular skeletal muscle mass (ASM) was calculated by the sum of muscle masses of the four limbs (kg), and expressed as percent of body weight. Results: Subjects were stratified according to tertiles of RMM. The prevalence of abdominal obesity, dyslipidemia, insulin resistance, metabolic syndrome, NAFLD as well as biopsy-proven nonalcoholic steatohepatitis (NASH) was significantly increased in the lowest tertile of RMM. After controlling for age, sex and Tanner stage, children in the lowest tertile of RMM had an increased risk for NAFLD (OR= 2.80, 95% CI=1.57-5.02) compared to those in the other two tertiles. This association persisted after additional adjustments for clinical and metabolic variables. Similarly, the risk of NAFLD in the lowest tertile of ASM/weight index was significantly higher compared to those in the other two tertiles after adjustment for the above confounders. Conclusions: This is the first study to establish an independent association between low muscle mass and NAFLD/NASH in overweight/obese youths. Considering the worldwide increase of pediatric obesity, measurements of muscle mass may serve as useful method of identifying among obese children those at high metabolic risk who may need intensive lifestyle interventions to prevent NAFLD and its progression.
Project description:Body weight reduction leads to improvement of nonalcoholic fatty liver disease (NAFLD), but the contributions of body composition modification on its improvement have not been clarified yet. We performed a retrospective cohort study in a Japanese university hospital to clarify the effect of body fat reduction on the improvement of hepatic stiffness as well as hepatic steatosis. The skeletal muscle mass index (SMI, kg/m2), fat to muscle mass ratio, and the change in fat to muscle mass ratio after 1 year from baseline were calculated. Controlled attenuation parameter (CAP, dB/m) and liver stiffness measurement (LSM, kPa) were evaluated by elastography. Primary outcome was set as the association of the change of fat to muscle mass ratio after 1 year from baseline with the change of liver stiffness measurement. One hundred and seventeen patients (59 men and 58 women) completed the study. The average age was 63.5 years, and baseline CAP and LSM were 273.4 ± 53.5 dB/m and 6.3 ± 3.4 kPa, respectively. After 1 year, body mass index (BMI), SMI, and LSM decreased. Multiple regression analyses demonstrated that change in fat to muscle mass ratio was associated with the change in CAP (ß = 0.38, p < 0.001) or LSM (ß = 0.21, p = 0.026). The reduction of fat to muscle mass ratio was associated with improvement in liver stiffness, but the reduction of BMI was not.
Project description:OBJECTIVE:We examined whether racial differences in liver fat are associated with the differences in abdominal fat distribution or cardiorespiratory fitness (CRF). METHODS:Participants included 57 black and white obese boys (12-18?years). Total and abdominal fat was measured by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging, respectively. CRF was measured using a maximal graded treadmill test with the use of standard open-circuit spirometry techniques until volitional fatigue. Liver fat was measured using a 3T proton magnetic resonance spectroscopy. Fatty liver was defined as having liver fat ?5%. RESULTS:In the sample, 16.1% of black boys and 30.8% of white boys had fatty liver. Liver fat was associated (P???.05) with body mass index (BMI) percentile (r?=?0.28), total fat (r?=?0.31), waist circumference (r?=?0.38), visceral fat (r?=?0.62), abdominal subcutaneous adipose tissue (r?=?0.30), and CRF (r?=?-0.27) adjusting for age and race. White boys had greater liver fat than black boys with adjustment for age and differences in BMI percentile or CRF, but not with waist circumference or visceral fat (P?>?.05). In a model with age, ethnicity, total body fat, fat-free mass, visceral fat, abdominal subcutaneous fat, and CRF, visceral fat was the only factor to be independently associated with increased odds of having fatty liver (OR?=?1.12; 95% CI: 1.04-1.21; P?=?.003). CONCLUSION:The racial disparities in liver fat between obese black vs white adolescents are explained, in part, by differences in visceral fat.
Project description:Paediatric non-alcoholic fatty liver disease (NAFLD) is considered the most common early driver of chronic liver disease. The aim of this study was to examine whether grip strength moderates the association between anthropometric and body composition parameters and controlled attenuation parameter (CAP), an indicator of fat deposits in the liver, in children and adolescents with excess of adiposity. A total of 127 adolescents (67% girls) aged between 11 and 17, attending two public schools in Bogotá (Colombia), who had an axiological evaluation of obesity were included in this study. A grip strength test was assessed as an indicator of muscular strength, and cardiorespiratory fitness by maximal oxygen uptake was assessed using the 20 m shuttle-run test. Waist circumference (WC), waist-to-height ratio (WHtR), fat mass, and visceral adipose tissue (VAT) (cm³) were included as anthropometric and body composition measures. CAP was determined with a FibroScan® 502 Touch device (Echosens, Paris, France). The anthropometric and body composition parameters including WC, WHtR, fat mass, and VAT were positively associated with the CAP (range ? = 0.423 to 0.580), slightly reduced after being adjusted for handgrip strength/weight. The Johnson-Neyman technique revealed a significant inverse relationship between WC, WHtR, VAT, and CAP when grip strength normalized by body mass was above but not equal to or below 0.475 (8.1% of the sample), 0.469 (8.9% of the sample), and 0.470 (8.5% of the sample), respectively. In conclusion, grip strength adjusted by body mass, has a moderating effect on the association between anthropometric and body composition parameters (including WC, WHtR, and VAT) and CAP in in children and adolescents with excess of adiposity, suggesting the importance of promoting muscular strength during paediatric population in order to prevent NAFLD.
Project description:The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the liver status in overweight or obese subjects with NAFLD after a 6 months follow-up. Ninety-eight individuals from the Fatty Liver in Obesity (FLiO) study were randomized into two groups and followed different energy-restricted diets. Subjects were evaluated at baseline and after 6 months. Diet, anthropometry, body composition, and biochemical parameters were evaluated. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, and determination of transaminases. Both dietary groups significantly improved their metabolic and hepatic markers after the intervention, with no significant differences between them. Multivariate regression models evidenced a relationship between weight loss, adherence to the Mediterranean Diet (MedDiet), and a decrease in liver fat content, predicting up to 40.9% of its variability after 6 months. Moreover, the antioxidant capacity of the diet was inversely associated with liver fat content. Participants in the group with a higher adherence to the MedDiet showed a greater reduction in body weight, total fat mass, and hepatic fat. These results support the benefit of energy-restricted diets, high adherence to the MedDiet, and high antioxidant capacity of the diet for the management of NAFLD in individuals with overweight or obesity.
Project description:Despite the benefits of pioglitazone in the treatment of non-alcoholic fatty liver disease (NAFLD), many treated patients continue to experience disease progression. We aimed to investigate the additive effect of ipragliflozin on NAFLD in patients with type 2 diabetes treated with metformin and pioglitazone. In this 24-week randomized controlled trial, 44 patients with type 2 diabetes and comorbid NAFLD were either randomized to receive 50 mg/day of ipragliflozin as an add-on treatment (n = 29) or maintained on metformin and pioglitazone (n = 15). The fatty burden was assessed using the fatty liver index, NAFLD liver fat score, and controlled attenuation parameter (CAP). Changes in fat and muscle depots were measured by dual-energy x-ray absorptiometry and abdominal computed tomography scans. The enrolled patients were relatively controlled (mean baseline glycated hemoglobin of 6.6% ± 0.6%) and centrally obese (mean waist circumference of 101.6 ± 10.9 cm). At week 24, patients in the ipragliflozin add-on group exhibited reduced hepatic fat content (fatty liver index: -9.8 ± 1.9, p = 0.002; NAFLD liver fat score: -0.5 ± 0.2, p = 0.049; CAP: -8.2 ± 7.8 dB/m2, p = 0.133). Ipragliflozin add-on therapy also reduced whole-body visceral fat and the ratio of visceral to subcutaneous fat (change in whole-body visceral fat: -69.6 ± 21.5 g; change in abdominal visceral fat: -26.2 ± 3.7 cm2; abdominal visceral to subcutaneous fat ratio: -0.15 ± 0.04; all p < 0.05). In conclusion, ipragliflozin treatment significantly ameliorates liver steatosis and reduces excessive fat in euglycemic patients with type 2 diabetes and NAFLD taking metformin and pioglitazone.
Project description:OBJECTIVE:Increased hepatic expression of dipeptidyl peptidase 4 (DPP4) is associated with non-alcoholic fatty liver disease (NAFLD). Whether this is causative for the development of NAFLD is not yet clarified. Here we investigate the effect of hepatic DPP4 overexpression on the development of liver steatosis in a mouse model of diet-induced obesity. METHODS:Plasma DPP4 activity of subjects with or without NAFLD was analyzed. Wild-type (WT) and liver-specific Dpp4 transgenic mice (Dpp4-Liv-Tg) were fed a high-fat diet and characterized for body weight, body composition, hepatic fat content and insulin sensitivity. In vitro experiments on HepG2 cells and primary mouse hepatocytes were conducted to validate cell autonomous effects of DPP4 on lipid storage and insulin sensitivity. RESULTS:Subjects suffering from insulin resistance and NAFLD show an increased plasma DPP4 activity when compared to healthy controls. Analysis of Dpp4-Liv-Tg mice revealed elevated systemic DPP4 activity and diminished active GLP-1 levels. They furthermore show increased body weight, fat mass, adipose tissue inflammation, hepatic steatosis, liver damage and hypercholesterolemia. These effects were accompanied by increased expression of PPAR? and CD36 as well as severe insulin resistance in the liver. In agreement, treatment of HepG2 cells and primary hepatocytes with physiological concentrations of DPP4 resulted in impaired insulin sensitivity independent of lipid content. CONCLUSIONS:Our results give evidence that elevated expression of DPP4 in the liver promotes NAFLD and insulin resistance. This is linked to reduced levels of active GLP-1, but also to auto- and paracrine effects of DPP4 on hepatic insulin signaling.
Project description:Type 2 diabetes mellitus (T2DM) is associated with a high incidence of non-alcoholic fatty liver disease (NAFLD) related to obesity and insulin resistance. Currently, medical interventions for NAFLD have focused on diet control and exercise to reduce body weight, and there is a requirement for effective pharmacological therapies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote the urinary excretion of glucose by blocking its reabsorption in renal proximal tubules. SGLT2 inhibitors lower blood glucose independent of insulin action and are expected to reduce body weight because of urinary calorie loss. Here we show that an SGLT2 inhibitor ipragliflozin improves hepatic steatosis in high-fat diet-induced and leptin-deficient (ob/ob) obese mice irrespective of body weight reduction. In the obese mice, ipragliflozin-induced hyperphagia occurred to increase energy intake, attenuating body weight reduction with increased epididymal fat mass. There is an inverse correlation between weights of liver and epididymal fat in ipragliflozin-treated obese mice, suggesting that ipragliflozin treatment promotes normotopic fat accumulation in the epididymal fat and prevents ectopic fat accumulation in the liver. Despite increased adiposity, ipragliflozin ameliorates obesity-associated inflammation and insulin resistance in epididymal fat. Clinically, ipragliflozin improves liver dysfunction in patients with T2DM irrespective of body weight reduction. These findings provide new insight into the effects of SGLT2 inhibitors on energy homeostasis and fat accumulation and indicate their potential therapeutic efficacy in T2DM-associated hepatic steatosis.
Project description:Background: Emerging evidence suggests that structural adventitial modifications and perivascular adipose tissue (PAT) may have a role in early atherogenesis. In a cohort of children and adolescents, we explored (1) the association of carotid extra-media thickness (cEMT), an ultrasound measure whose main determinants are arterial adventitia and PAT, with obesity and its cardiometabolic complications; and (2) the interplay between cEMT and endothelial function. Methods: The study participants included 286 youths (age, 6-16 years; 154 boys, and 132 girls). Anthropometric and laboratory parameters, liver ultrasound, vascular structure measures [cEMT and carotid intima-media thickness (cIMT)], endothelial function [brachial artery flow-mediated dilation (FMD)] were obtained in all subjects. Non-alcoholic fatty liver disease (NAFLD) was diagnosed in the presence of hepatic fat on ultrasonography, in the absence of other causes of liver disease. Diagnosis of metabolic syndrome (MetS) was established on the basis of three or more of the following cardiovascular disease (CVD) risk variables: abdominal obesity, high triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure (BP), and impaired fasting glucose. Results: cEMT demonstrated significant associations with body-mass index (BMI) and waist circumference (WC), BP, insulin resistance, NAFLD, and inflammation. No association was found between cEMT and lipid values, and between cEMT and MetS. A stepwise multivariate linear regression analysis indicated that WC (? coefficient, 0.35; P < 0.0001) was the only determinant of cEMT, independently of other major cardiometabolic risk factors. Further adjustment for cIMT did not significantly alter this association. FMD was correlated to age, Tanner stage, total and abdominal obesity, BP, NAFLD, and cEMT. The association between FMD and cEMT was independent of age, sex, Tanner stage, WC, and BMI (? coefficient, -0.14; P = 0.027). After controlling for CVD risk factors and basal brachial artery diameter, cEMT remained associated with FMD (? coefficient, -0.11; P = 0.049). Conclusions: In youths, cEMT is associated with abdominal fat, a well-established body fat depot with important implications for cardiovascular diseases. Furthermore, cEMT is related to FMD, suggesting that arterial adventitia and PAT may be involved in the early changes in endothelial function.