Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins

Abstract

-Järvinen. Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins. Am J Physiol Endocrinol Metab 288: E768 -E774, 2005. First published December 7, 2004; doi:10.1152/ajpendo.00381.2004.-We determined whether acquired obesity is associated with increases in liver or intra-abdominal fat or impaired insulin sensitivity by studying monozygotic (MZ) twin pairs discordant and concordant for obesity. We studied nineteen 24-to 27-yr-old MZ twin pairs, with intrapair differences in body weight ranging from 0.1 to 24.7 kg [body mass index (BMI) range 20.0-33.9 kg/m 2 ], identified from a population-based FinnTwin16 sample. Fat distribution was determined by magnetic resonance imaging, percent body fat by dual-energy X-ray absorptiometry, liver fat by proton spectroscopy, insulin sensitivity by measuring the fasting insulin concentration, and whole body insulin sensitivity by the euglycemic insulin clamp technique. Intrapair differences in BMI were significantly correlated with those in intra-abdominal fat (r ϭ 0.82, P Ͻ 0.001) and liver fat (r ϭ 0.57, P ϭ 0.010). Intrapair differences in fasting insulin correlated with those in subcutaneous abdominal (r ϭ 0.60, P ϭ 0.008), intra-abdominal (r ϭ 0.75, P ϭ 0.0001) and liver (r ϭ 0.49, P ϭ 0.048) fat. Intrapair differences in whole body insulin sensitivity correlated with those in subcutaneous abdominal (r ϭ Ϫ0.72, P ϭ 0.001) and intraabdominal (r ϭ Ϫ0.55, P ϭ 0.015) but not liver (r ϭ Ϫ0.20, P ϭ 0.20) fat. We conclude that acquired obesity is associated with increases in intraabdominal and liver fat and insulin resistance, independent of genetic factors. body composition; fatty liver; genes; environment; spectroscopy; magnetic resonance imaging RECENT STUDIES HAVE IDENTIFIED fat accumulation in the liver as a novel proximal correlate of insulin resistance (2,5,15,29,36). Although subcutaneous and especially intra-abdominal fat are closely correlated with insulin resistance (6,14,30,37), liver fat has been associated with features of insulin resistance independent of obesity and fat distribution in several studies (25,35,45). Increased liver fat has also been shown to predict type 2 diabetes independently of obesity (7, 47). In both mice (2,5,15,29,36) and humans (28), severe insulin resistance can be observed in the absence of subcutaneous and intra-abdominal fat. In such mice, hepatic insulin resistance can be abolished by subcutaneous fat transplantation (15). These data raise the question of whether acquired obesity indeed regulates liver fat content. Alternative regulators would be genetic factors and acquired factors other than obesity, such as dietary fat content and composition (24, 44).Study of monozygotic (MZ) twin pairs discordant for obesity offers a unique opportunity to determine whether acquired obesity increases liver fat. Because MZ twins are perfectly matched for genes as well as for age, sex, and ethnicity and MZ twins also often share the same environment, study of young adults...

A comparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose, fasting insulin, and glycated hemoglobin in women with and without diabetes

“…Data of women with and without diabetes were analyzed separately and a formal test for interaction between age adjusted ALT and GGT (each) and diabetes in their association with fasting glucose, fasting insulin and HbA1c was conducted. As evidence shows that the fat accumulation in the liver is associated with obesity (for example, Pietilainen et al 23 ), we also conducted analyses stratified by central obesity for data of women without diabetes.…”

Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes

“…More recently it was suggested that ectopic fat accumulation within the liver may be also associated with peripheral and hepatic insulin resistance in nondiabetic individuals [5,6] and is common in obese patients with type 2 diabetes [20]. Some authors suggest that fatty liver represents a body composition manifestation of obesity and visceral adiposity in insulin-resistant subjects [21], but at the same time they suggest that the impact on insulin sensitivity is determined regardless of intra-abdominal and overall adiposity [6]. Moreover, fatty liver accumulation appears to be peculiarly associated with hepatic insulin resistance; in fact moderate weight reduction in obese patients with type 2 diabetes was associated with reduced IHF content and improvement of hepatic insulin sensitivity but no change in insulin-stimulated peripheral glucose metabolism [22].…”

Causes and consequences of obesity: the contribution of recent twin studies

“…5 The heavier co-twin was found to have 64% more abdominal subcutaneous fat, 93% more intra-abdominal fat and 284% more liver fat than the lean co-twin. Environmental influences independent from acquired obesity on liver fat were evaluated based on questionnaires and food diaries.…”

“…Analysis of data from food diaries showed that the percentage of energy from fat (r ¼ 0.37, P ¼ 0.02) and saturated fat (r ¼ 0.38, P ¼ 0.005) did correlate with liver fat. 5 The effects of acquired obesity, however, varied considerably between the twin pairs; although in all cases the obese co-twin had an increased amount of subcutaneous and visceral fat, some of the pairs were clearly more prone to hepatic fat accumulation, regardless of the weight difference---presumably because of strong genetic influences on this fat depot. 45 Calculations of the intra-pair differences in fat accumulation across different depots revealed that subcutaneous fat accumulation explains roughly twice as much of the variation in intra-abdominal (42 --67%) than liver fat (12 --33%).…”

“…Non-obese co-twins are set as 1.0, and the obese co-twins' values are the ratio of obese to non-obese co-twins' values. Data are derived from Pietilainen et al 5 ; Mustelin et al 10 ; Pietilainen et al 12 fS-insulin, fasting serum insulin; Ia, intra-abdominal; mtDNA, mitochondrial DNA; Sc fat, subcutaneous abdominal fat. *Po0.05, **Po0.01, ***Po0.001.…”