Elevated Circulating Glutamate Is Associated With Subclinical Atherosclerosis Independently of Established Risk Markers: A Cross-Sectional Study

Abstract Objective Elevated plasma glutamate levels are associated with an increased risk of cardiovascular disease (CVD). Because plasma glutamate levels are also strongly associated with visceral adiposity, nonalcoholic fatty liver disease, insulin resistance, and high circulating levels of branched-chain amino acids (BCAAs), it is unknown to what extent elevated circulating glutamate is an independent marker of an increased risk of atherosclerosis. Methods Plasma levels of glutamate and BCAAs were measured in 102 individuals who were precisely phenotyped for body fat mass and distribution (magnetic resonance [MR] tomography), liver fat content (1H-MR spectroscopy), insulin sensitivity (oral glucose tolerance test and hyperinsulinemic, euglycemic clamp [N = 57]), and carotid intima media thickness (cIMT). Results Plasma glutamate levels, adjusted for age, sex, body fat mass, and visceral fat mass, correlated positively with liver fat content and cIMT (all std β ≥ .22, all P ≤ .023) and negatively with insulin sensitivity (std β ≤ –.31, P ≤ .002). Glutamate levels also were associated with cIMT, independently of additional adjustment for liver fat content, insulin sensitivity and BCAAs levels (std β ≥ .24, P ≤ .02). Furthermore, an independent positive association of glutamate and interleukin-6 (IL-6) levels was observed (N = 50; std β = .39, P = .03). Although glutamate, adjusted for age, sex, body fat mass, and visceral fat mass, also correlated positively with cIMT in this subgroup (std β = .31, P = .02), after additional adjustment for the parameters liver fat content, insulin sensitivity, BCAAs, or IL-6 levels, adjustment for IL-6 most strongly attenuated this relationship (std β = .28, P = .05). Conclusions Elevated plasma glutamate levels are associated with increased cIMT, independently of established CVD risk factors, and this relationship may in part be explained by IL-6-associated subclinical inflammation.

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Liver Fat Content and Body Fat Distribution in Youths with Excess Adiposity

Journal of Clinical Medicine ◽

10.3390/jcm7120528 ◽

2018 ◽

Vol 7 (12) ◽

pp. 528 ◽

Cited By ~ 3

Author(s):

Robinson Ramírez-Vélez ◽

Mikel Izquierdo ◽

Jorge Correa-Bautista ◽

María Correa-Rodríguez ◽

Jacqueline Schmidt-RioValle ◽

...

Keyword(s):

Body Fat ◽

Fat Mass ◽

Fat Distribution ◽

Fat Content ◽

Body Fat Distribution ◽

Healthy Diet ◽

Liver Fat ◽

Liver Fat Content ◽

Excess Adiposity ◽

Distribution Parameters

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.

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Insulin Sensitivity Is Correlated with Subcutaneous but Not Visceral Body Fat in Overweight and Obese Prepubertal Children

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2089 ◽

2008 ◽

Vol 93 (6) ◽

pp. 2122-2128 ◽

Cited By ~ 60

Author(s):

Claudio Maffeis ◽

Riccardo Manfredi ◽

Maddalena Trombetta ◽

Silvia Sordelli ◽

Monica Storti ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Body Fat ◽

Fat Distribution ◽

Fat Content ◽

Liver Fat ◽

P Value ◽

Inflammation Markers ◽

Liver Fat Content ◽

Prepubertal Children

Abstract Aim: Our aim was to explore the relationship between insulin sensitivity, body fat distribution, ectopic (liver and skeletal muscle) fat deposition, adipokines (leptin and adiponectin), and inflammation markers (highly sensitive C-reactive protein, IL-6, IL-10, and TNF-α) in prepubertal children. Subjects and Methods: Thirty overweight and obese children (16 males and 14 females with body mass index z-score range of 1.1–3.2) were recruited. Body fat distribution and fat accumulation in liver and skeletal muscle were measured using magnetic resonance imaging. Insulin sensitivity was assessed by iv glucose tolerance test. Results: Insulin sensitivity was associated with sc abdominal adipose tissue (SAT) (r = −0.52; P < 0.01) and liver fat content (r = −0.44; P < 0.02) but not with visceral abdominal adipose tissue (VAT) (r = −0.193; P value not significant) and fat accumulation in skeletal muscle (r = −0.210; P value not significant). Adipokines, but not inflammation markers, were significantly correlated to insulin sensitivity. VAT correlated with C-reactive protein (r = 0.55; P < 0.01) as well as adiponectin (r = −0.53; P <0.01). Multiple regression analysis showed that only SAT and liver fat content were independently correlated to insulin sensitivity (P < 0.01; 20 and 16% of explained variance, respectively). Conclusions: In overweight and moderately obese prepubertal children, insulin sensitivity was negatively correlated with SAT and liver fat content. Furthermore, contrary to adults, VAT and inflammation markers were not correlated with insulin sensitivity in children.

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Branched-chain amino acid metabolism, insulin sensitivity and liver fat response to exercise training in sedentary dysglycaemic and normoglycaemic men

Diabetologia ◽

10.1007/s00125-020-05296-0 ◽

2020 ◽

Author(s):

Sindre Lee ◽

Hanne L. Gulseth ◽

Torgrim M. Langleite ◽

Frode Norheim ◽

Thomas Olsen ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Plasma Concentration ◽

Fat Mass ◽

Liver Fat ◽

Liver Fat Content ◽

Mrna Sequencing ◽

Branched Chain

Abstract Aims/hypothesis Obesity and insulin resistance may be associated with elevated plasma concentration of branched-chain amino acids (BCAAs) and impaired BCAA metabolism. However, it is unknown whether the insulin-sensitising effect of long-term exercise can be explained by concomitant change in BCAAs and their metabolism. Methods We included 26 sedentary overweight and normal-weight middle-aged men from the MyoGlu clinical trial, with or without dysglycaemia, for 12 weeks of supervised intensive exercise intervention, including two endurance and two resistance sessions weekly. Insulin sensitivity was measured as the glucose infusion rate (GIR) from a hyperinsulinaemic−euglycaemic clamp. In addition, maximum oxygen uptake, upper and lower body strength and adipose tissue depots (using MRI and spectroscopy) were measured, and subcutaneous white adipose tissue (ScWAT) and skeletal muscle (SkM) biopsies were harvested both before and after the 12 week intervention. In the present study we have measured plasma BCAAs and related metabolites using CG-MS/MS and HPLC-MS/MS, and performed global mRNA-sequencing pathway analysis on ScWAT and SkM. Results In MyoGlu, men with dysglycaemia displayed lower GIR, more fat mass and higher liver fat content than normoglycaemic men at baseline, and 12 weeks of exercise increased GIR, improved body composition and reduced liver fat content similarly for both groups. In our current study we observed higher plasma concentrations of BCAAs (14.4%, p = 0.01) and related metabolites, such as 3-hydroxyisobutyrate (19.4%, p = 0.034) in dysglycaemic vs normoglycaemic men at baseline. Baseline plasma BCAA levels correlated negatively to the change in GIR (ρ = −0.41, p = 0.037) and $$ \dot{V}{\mathrm{O}}_{2\max } $$ V ̇ O 2 max (ρ = −0.47, p = 0.015) after 12 weeks of exercise and positively to amounts of intraperitoneal fat (ρ = 0.40, p = 0.044) and liver fat (ρ = 0.58, p = 0.01). However, circulating BCAAs and related metabolites did not respond to 12 weeks of exercise, with the exception of isoleucine, which increased in normoglycaemic men (10 μmol/l, p = 0.01). Pathway analyses of mRNA-sequencing data implied reduced BCAA catabolism in both SkM and ScWAT in men with dysglycaemia compared with men with normoglycaemia at baseline. Gene expression levels related to BCAA metabolism correlated positively with GIR and markers of mitochondrial content in both SkM and ScWAT, and negatively with fat mass generally, and particularly with intraperitoneal fat mass. mRNA-sequencing pathway analysis also implied increased BCAA metabolism after 12 weeks of exercise in both groups and in both tissues, including enhanced expression of the gene encoding branched-chain α-ketoacid dehydrogenase (BCKDH) and reduced expression of the BCKDH phosphatase in both groups and tissues. Gene expression of SLC25A44, which encodes a mitochondrial BCAA transporter, was increased in SkM in both groups, and gene expression of BCKDK, which encodes BCKDH kinase, was reduced in ScWAT in dysglycaemic men. Mediation analyses indicated a pronounced effect of enhanced SkM (~53%, p = 0.022), and a moderate effect of enhanced ScWAT (~18%, p = 0.018) BCAA metabolism on improved insulin sensitivity after 12 weeks of exercise, based on mRNA sequencing. In comparison, plasma concentration of BCAAs did not mediate any effect in this regard. Conclusion/interpretation Plasma BCAA concentration was largely unresponsive to long-term exercise and unrelated to exercise-induced insulin sensitivity. On the other hand, the insulin-sensitising effect of long-term exercise in men may be explained by enhanced SkM and, to a lesser degree, also by enhanced ScWAT BCAA catabolism.

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No Independent Association of Circulating Fetuin-A with Insulin Sensitivity in Young Women

Hormone and Metabolic Research ◽

10.1055/a-1216-4405 ◽

2020 ◽

Vol 52 (11) ◽

pp. 809-814

Author(s):

Sabrina Reif ◽

Sarah Moschko ◽

Christina Gar ◽

Uta Ferrari ◽

Nina Hesse ◽

...

Keyword(s):

Diabetes Mellitus ◽

Metabolic Syndrome ◽

Insulin Sensitivity ◽

Young Women ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Fetuin A ◽

The Metabolic Syndrome ◽

Independent Association

AbstractAnimal data link high circulating fetuin-A to low insulin sensitivity and observational studies identify the hepatokine as a marker of future incident type 2 diabetes mellitus in humans. However, a recent, well-powered Mendelian randomization study finds no causal role. We therefore tested in a deeply-phenotyped human cohort if circulating fetuin-A correlates independently with insulin sensitivity and how it relates to the metabolic syndrome and ectopic fat deposition. We analyzed data from 290 young women with and without recent gestational diabetes mellitus. We found that circulating fetuin-A correlates inversely with insulin sensitivity in univariate analyses, but that this correlation is lost after adjustment for markers of the metabolic syndrome and of fatty liver. Additionally, we investigated which fat compartment associates most strongly with circulating fetuin-A. In whole body MRI data from a subcohort of 152 women, this was liver fat content. We conclude that high circulating fetuin-A occurs as part of the metabolic syndrome in young women and associates most strongly with liver fat content. Its close link to the metabolic syndrome may also cause the inverse correlation of circulating fetuin-A with insulin sensitivity as we found no independent association.

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Effect of liver fat on insulin clearance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00444.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. E1709-E1715 ◽

Cited By ~ 129

Author(s):

Anna Kotronen ◽

Satu Vehkavaara ◽

Anneli Seppälä-Lindroos ◽

Robert Bergholm ◽

Hannele Yki-Järvinen

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Fat Content ◽

Insulin Clearance ◽

Liver Fat ◽

Hepatic Insulin Resistance ◽

Model Assessment ◽

Liver Fat Content ◽

Hepatic Insulin Sensitivity ◽

Impaired Insulin

A fatty liver is associated with fasting hyperinsulinemia, which could reflect either impaired insulin clearance or hepatic insulin action. We determined the effect of liver fat on insulin clearance and hepatic insulin sensitivity in 80 nondiabetic subjects [age 43 ± 1 yr, body mass index (BMI) 26.3 ± 0.5 kg/m2]. Insulin clearance and hepatic insulin resistance were measured by the euglycemic hyperinsulinemic (insulin infusion rate 0.3 mU·kg−1·min−1for 240 min) clamp technique combined with the infusion of [3-3H]glucose and liver fat by proton magnetic resonance spectroscopy. During hyperinsulinemia, both serum insulin concentrations and increments above basal remained ∼40% higher ( P < 0.0001) in the high (15.0 ± 1.5%) compared with the low (1.8 ± 0.2%) liver fat group, independent of age, sex, and BMI. Insulin clearance (ml·kg fat free mass−1·min−1) was inversely related to liver fat content ( r = −0.52, P < 0.0001), independent of age, sex, and BMI ( r = −0.37, P = 0.001). The variation in insulin clearance due to that in liver fat (range 0–41%) explained on the average 27% of the variation in fasting serum (fS)-insulin concentrations. The contribution of impaired insulin clearance to fS-insulin concentrations increased as a function of liver fat. This implies that indirect indexes of insulin sensitivity, such as homeostatic model assessment, overestimate insulin resistance in subjects with high liver fat content. Liver fat content correlated significantly with fS-insulin concentrations adjusted for insulin clearance ( r = 0.43, P < 0.0001) and with directly measured hepatic insulin sensitivity ( r = −0.40, P = 0.0002). We conclude that increased liver fat is associated with both impaired insulin clearance and hepatic insulin resistance. Hepatic insulin sensitivity associates with liver fat content, independent of insulin clearance.

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Metabolomics: a search for biomarkers of visceral fat and liver fat content

Metabolomics ◽

10.1007/s11306-019-1599-x ◽

2019 ◽

Vol 15 (10) ◽

Cited By ~ 2

Author(s):

Sebastiaan Boone ◽

Dennis Mook-Kanamori ◽

Frits Rosendaal ◽

Martin den Heijer ◽

Hildo Lamb ◽

...

Keyword(s):

Visceral Fat ◽

Diagnostic Value ◽

Fat Content ◽

Metabolite Concentration ◽

Liver Fat ◽

Plasma Metabolites ◽

Liver Fat Content ◽

Cross Sectional ◽

Fat Depots ◽

Cardiometabolic Disorders

Abstract Intoduction Excess visceral and liver fat are known risk factors for cardiometabolic disorders. Metabolomics might allow for easier quantification of these ectopic fat depots, instead of using invasive and costly tools such as MRI or approximations such as waist circumference. Objective We explored the potential use of plasma metabolites as biomarkers of visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC). Methods We performed a cross-sectional analysis of a subset of the Netherlands Epidemiology of Obesity study. Plasma metabolite profiles were determined using the Biocrates AbsoluteIDQ p150 kit in 176 individuals with normal fasting plasma glucose. VAT was assessed with magnetic resonance imaging and HTGC with proton-MR spectroscopy. We used linear regression to investigate the associations of 190 metabolite variables with VAT and HTGC. Results After adjustment for age, sex, total body fat, currently used approximations of visceral and liver fat, and multiple testing, three metabolite ratios were associated with VAT. The strongest association was the lysophosphatidylcholines to total phosphatidylcholines (PCs) ratio [− 14.1 (95% CI − 21.7; − 6.6) cm2 VAT per SD of metabolite concentration]. Four individual metabolites were associated with HTGC, especially the diacyl PCs of which C32:1 was the strongest at a 1.31 (95% CI 1.14; 1.51) fold increased HTGC per SD of metabolite concentration. Conclusion Metabolomics may be a useful tool to identify biomarkers of visceral fat and liver fat content that have added diagnostic value over current approximations. Replication studies are required to validate the diagnostic value of these metabolites.

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Potential effects of reduced red meat compared with increased fiber intake on glucose metabolism and liver fat content: a randomized and controlled dietary intervention study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy307 ◽

2019 ◽

Vol 109 (2) ◽

pp. 288-296 ◽

Cited By ~ 3

Author(s):

Caroline Willmann ◽

Martin Heni ◽

Katarzyna Linder ◽

Robert Wagner ◽

Norbert Stefan ◽

...

Keyword(s):

Body Fat ◽

Intervention Study ◽

Dietary Intervention ◽

Fat Content ◽

Red Meat ◽

Liver Fat ◽

Fiber Intake ◽

Liver Fat Content ◽

Meat Intake

ABSTRACT Background Epidemiological studies suggest that an increased red meat intake is associated with a higher risk of type 2 diabetes, whereas an increased fiber intake is associated with a lower risk. Objectives We conducted an intervention study to investigate the effects of these nutritional factors on glucose and lipid metabolism, body-fat distribution, and liver fat content in subjects at increased risk of type 2 diabetes. Methods This prospective, randomized, and controlled dietary intervention study was performed over 6 mo. All groups decreased their daily caloric intake by 400 kcal. The “control” group (N = 40) only had this requirement. The “no red meat” group (N = 48) in addition aimed to avoid the intake of red meat, and the “fiber” group (N = 44) increased intake of fibers to 40 g/d. Anthropometric parameters and frequently sampled oral glucose tolerance tests were performed before and after intervention. Body-fat mass and distribution, liver fat, and liver iron content were assessed by MRI and single voxel proton magnetic resonance spectroscopy. Results Participants in all groups lost weight (mean 3.3 ± 0.5 kg, P < 0.0001). Glucose tolerance and insulin sensitivity improved (P < 0.001), and body and visceral fat mass decreased in all groups (P < 0.001). These changes did not differ between groups. Liver fat content decreased significantly (P < 0.001) with no differences between the groups. The decrease in liver fat correlated with the decrease in ferritin during intervention (r2 = 0.08, P = 0.0021). This association was confirmed in an independent lifestyle intervention study (Tuebingen Lifestyle Intervention Program, N = 229, P = 0.0084). Conclusions Our data indicate that caloric restriction leads to a marked improvement in glucose metabolism and body-fat composition, including liver-fat content. The marked reduction in liver fat might be mediated via changes in ferritin levels. In the context of caloric restriction, there seems to be no additional beneficial impact of reduced red meat intake and increased fiber intake on the improvement in cardiometabolic risk parameters. This trial was registered at clinicaltrials.gov as NCT03231839.

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Associations of Hair Cortisol Concentrations with General and Organ Fat Measures in Childhood

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa785 ◽

2020 ◽

Author(s):

Florianne O L Vehmeijer ◽

Susana Santos ◽

Romy Gaillard ◽

Yolanda B de Rijke ◽

Trudy Voortman ◽

...

Keyword(s):

Fat Mass ◽

Visceral Fat ◽

Standard Deviation Score ◽

Population Based ◽

Liver Fat ◽

Hair Cortisol ◽

Fat Mass Index ◽

Nonalcoholic Fatty Liver ◽

Increased Risk ◽

Fat Fraction

Abstract Context Stress may lead to an adverse body fat distribution from childhood onwards. Objective To examine the associations of hair cortisol concentration (HCC) at 6 years with general and organ fat measures, risk of overweight, and nonalcoholic fatty liver disease (NAFLD) at 10 years and to assess whether these were independent of adiposity measures at 6 years. Design, Setting and participants HCCs were measured in hair of 6-year-old children (n = 2042) participating in the Generation R Study, a population-based prospective cohort study. Main Outcome Measures Body mass index (BMI), fat mass index measured by dual-energy X-ray absorptiometry scan, and visceral fat index, pericardial fat index, liver fat fraction measured by magnetic resonance imaging and risk of overweight and NAFLD were obtained at 10 years. Results The associations of higher HCC at 6 years, with higher BMI, fat mass index, and increased risk of overweight at age 10 years are explained by the relationships observed at 6 years. HCCs at 6 years were associated with a higher liver fat fraction (difference 0.11 liver fat fraction standard deviation score; 95% confidence interval [CI] 0.03, 0.18) and a higher risk of NAFLD at 10 years (odds ratio 1.95; 95% CI 1.06, 3.56), independent of fat mass index at 6 years. HCCs were not associated with pericardial or visceral fat indices. Conclusions Higher HCCs at 6 years were associated with higher BMI, fat mass index, liver fat fraction, and higher risks of overweight and NAFLD at 10 years. Only the associations for liver fat fraction and NAFLD were independent of fat mass index at 6 years.

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Possible Role of Adiponectin and Insulin Sensitivity in Mediating the Favorable Effects of Lower Body Fat Mass on Blood Lipids

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-1062 ◽

2006 ◽

Vol 91 (5) ◽

pp. 1698-1704 ◽

Cited By ~ 19

Author(s):

B. Buemann ◽

A. Astrup ◽

O. Pedersen ◽

E. Black ◽

C. Holst ◽

...

Keyword(s):

Insulin Sensitivity ◽

Body Fat ◽

Fat Mass ◽

Blood Lipids ◽

Body Fat Mass ◽

Lower Body

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Similar Weight Loss Induces Greater Improvements in Insulin Sensitivity and Liver Function among Individuals with NAFLD Compared to Individuals without NAFLD

Nutrients ◽

10.3390/nu11030544 ◽

2019 ◽

Vol 11 (3) ◽

pp. 544 ◽

Cited By ~ 2

Author(s):

Ruth Schübel ◽

Tobias Nonnenmacher ◽

Disorn Sookthai ◽

Sandra Gonzalez Maldonado ◽

Solomon Sowah ◽

...

Keyword(s):

Weight Loss ◽

Insulin Sensitivity ◽

Liver Function ◽

Dietary Intervention ◽

Fat Content ◽

Metabolic Parameters ◽

Liver Fat ◽

Metabolic Effects ◽

Liver Fat Content ◽

Alcoholic Fatty Liver

Background: Preliminary evidence suggests that weight loss among obese has differential metabolic effects depending on the presence of non-alcoholic fatty liver disease (NAFLD). We assessed whether NAFLD predisposes to differential changes in liver fat content, liver function, and metabolic parameters upon diet-induced weight loss in a 50-week intervention trial. Methods: 143 overweight and obese non-smokers underwent a 12-week dietary intervention and a 38-week follow-up. Diet-induced changes in anthropometric measures, circulating biomarkers, and magnetic resonance (MR)-derived liver fat content and adipose tissue volumes were evaluated by mixed linear models stratifying by NAFLD at baseline. Results: The prevalence of NAFLD at baseline was 52%. Diet-induced weight loss after 12 (NAFLD: 4.8 ± 0.5%, No NAFLD: 5.1 ± 0.5%) and 50 weeks (NAFLD: 3.5 ± 0.7%, No NAFLD: 3.5 ± 0.9%) was similar in both groups, while the decrease in liver fat was significantly greater in the NAFLD group (week 12: 32.9 ± 9.5% vs. 6.3 ± 4.0%; week 50: 23.3 ± 4.4% vs. 5.0 ± 4.2%). Decreases in biomarkers of liver dysfunction (GGT, ALT, AST) and HOMA IR were also significantly greater in the NAFLD group. Other metabolic parameters showed no significant differences. Conclusion: Our data suggest that individuals with NAFLD show greater improvements of liver function and insulin sensitivity after moderate diet-induced weight loss than individuals without NAFLD.

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