Numerous MRI-studies of last years could identify different compartments of adipose tissue (AT) with varying impacts on metabolism [1-3]. The most important compartment seems to be visceral adipose tissue (VAT), which shows a strong association to insulin sensitivity and low grade inflammation [4]. Besides this, intrahepatic lipids (IHL) are involved in the pathogenesis of insulin resistance and several studies have proven the negative effect of increased IHL on insulin sensitivity [5]. To reduce the amount of AT in the different compartments, lifestyle interventions show promising results [6]. So far less is known about the effect of lifestyle intervention in terms of caloric restriction concerning the changes of liver volume, the amount of IHL and potentially connected effects on liver enzymes (Aspartate Transaminase = AST, Alanine Transaminase = ALT, Gamma-Glutamyl Transferase = GGT) and the subclinical low-grade inflammation. The aim of this study was to investigate potential associations between changes of liver volume, the amount of IHL and body weight during lifestyle interventions and to delineate potentially connected effects concerning changes of liver enzymes and the systemic low grade inflammation.Participants of this study were retrospectively selected from prospective cohort studies, characterizing the risk of developing a type 2 diabetes mellitus. All participants followed a caloric restriction diet for 6 months. 66 females and 45 males, mean age 48 years (22–71 years) with an average body mass index (BMI) of 31 kg/m² (20-47kg/m²) were enrolled. The liver volume was determined at the beginning and after 6 months by three-dimensional magnetic resonance imaging (3D-MRI, gradient-echo, opposed-phase, partition thickness 5 mm; see figure 1 c) and IHL were quantified by volume-selective ¹H-MRS (STEAM, TE/TR 10/4000ms, VOI 30x30x20mm³, 32 acq.; see figure 1 a and b). Anthropometric and metabolic data were assessed immediately after the MR examination. Blood samples were drawn to determine liver enzymes and the high sensitive C-reactive protein (hsCRP) as surrogate for systemic low grade inflammation. Gender stratified univariable correlation analyses between changes of liver volume (ΔLV), intrahepatic lipids (ΔIHL), body weight (ΔBW), liver enzymes (ΔAST, ΔALT, ΔGGT) and CRP (ΔhsCRP) were performed.Correlation analysis showed strong associations between ΔLV and ΔIHL in females and males (females: r = 0.64, p = <.0001; males: r = 0.51, p = 0.0006) but no significant associations to ΔBW. In females, a significant correlation between ΔIHL and ΔGGT (r = 0.45, p = 0.0002) respectively ΔALT (r = 0.28, p = 0.02) but not with ΔAST was present. Males showed no significant correlation between ΔIHL and ΔGGT, but with ΔALT (r = 0.49, p = 0.0008) and ΔAST (r = 0.40, p = 0.008). In females, but not in males a significant association between ΔIHL and ΔCRP could be identified (females: r = 0.45, p = 0.0002).Several compartments of physiological and ectopic lipids with varying impact on metabolism were described by MRI studies. Beyond VAT, IHL seems to have a dominating effect in causing a prediabetic metabolism. Lifestyle interventions are favored to influence the different compartments of AT. So far, little is known about the effects of lifestyle interventions in detail. Our results, after six months of caloric restriction show the reversibility of augmented liver volume in steatosis if it is possible to reduce IHL during lifestyle intervention. Therefore, the aim of lifestyle interventions should focus on reducing the amount of IHL and not on body weight leading to a positive effect on liver volume. The connected effects by reducing IHL on liver enzymes and the low grade inflammation seem to be gender specific. Hence, judging the effectivity of lifestyle intervention has to be done with regard to differing effects on liver enzymes and low grade inflammation in women and men.Changes of liver volume during lifestyle intervention are independent of changes of body weight and primarily determined by changes of IHL. Reduction of IHL seems to have gender-specific effects, mainly reducing GGT in females and ALT in males as well as having a positive effect in reducing the systemic low grade inflammation only in females. These results show the reversibility of augmented liver volume in steatosis and the resulting gender-specific benefits on metabolism.