previous neuroimaging studies demonstrated increased neural activation to food cues in obese compared to lean subjects in brain regions associated with reward , gustation , emotion , cognitive control and memory ( carnell et al . , 2012 ) . furthermore , structural alterations in obesity have been investigated using volume - based morphometry ( vbm ) . hereby obesity was associated with reduced gray matter ( gm ) density compared to lean subjects in prefrontal , somatosensory , insular , temporal , cerebellar and subcortical regions ( kurth et al . , 2013 ; pannacciulli et al . , 2006 ) . in general , obesity is determined by the body mass index ( bmi ) . however , it is well known that the risk of developing obesity related diseases is increased by specific body fat distribution and insulin resistance ( stefan et al . , 2008 ) . individuals with abdominal adiposity , showing increased visceral adipose tissue ( vat ) , have an enhanced risk of metabolic complications . 2013 ) demonstrated in young adults reduced gm volume exclusively in cerebellar areas with increased vat . ( 2010 ) found , in a middle - aged group , the strongest negative association between vat and total brain volume . in old subjects , higher vat was associated with reduced hippocampal volume and enlarged ventricles compared to lower vat ( isaac et al . , 2011 ) . besides gm volume , cortical thickness is a more specific ( ashburner and friston , 2001 ) and sensitive ( hutton et al . , 2009 ) furthermore , studies investigating gray matter changes in autism ( jiao et al . , 2010 ) and parkinson diseases ( pereira et al . , 2012 ) showed superior diagnostic classification using thickness - based models compared to vbm based models . cortical thickness may therefore be a more appropriate measure when assessing structural brain alterations in diseased brains . recently , cortical thinning was reported in obese compared to lean middle - aged adults in the anterior cingulate cortex ( acc ) , the anterior insula , the posterior parietal cortex ( hassenstab et al . , 2012 ) , the left superior frontal gyrus and the right medial orbitofrontal cortex ( ofc ) ( marques - iturria et al . , 2013 ) using atlas based averaged surface measures . thus far , the majority of the abovementioned structural studies focused on middle -aged to elderly individuals with severe obesity . it is , however , well known that additional factors are rather common in these populations like hypertension , elevated cholesterol and inflammatory processes , which potentially influence structural integrity and contribute to brain atrophy . hence , in the current study we assessed surface based cortical thickness to investigate adipose tissue ( i.e. vat ) related morphometric changes in lean , overweight and obese young to middle - aged adults . a total of 72 subjects ( 30 females ) were included in the study ( mean age ( years ) : 29.65 sd 8.15 ; mean bmi ( kg / m ) : 25.49 sd 5.18 ) . of the 72 subjects , 42 were lean ( bmi  <  25 ) , 17 overweight ( bmi 2530 ) and 13 obese ( bmi  >  30 ) . there were no significant sex differences for age and bmi . all subjects had normal metabolic status , no chronic diseases or psychiatric and neurological diseases . in particular , in the present study the average vat was 3.22  l in male and 1.80  l in female . based on published studies normative values in subjects with bmi below 30 range from 2.0 to 4.0  l in men and 1.5 to 2.0  l in women ( maislin et al . , 2012 ) . c - reactive protein levels were determined using standard clinical measure to exclude subjects with acute infection ( crp  > there was a significant difference between overweight / obese compared to lean subjects regarding their crp levels ( overweight / obese mean : 0.47 ( sd 0.57 )  mg / l , lean mean : 0.10 ( sd 0.21 )  mg / l ; t(68 )  =  3.79 , p  <  0.001 ) . the local ethics committee had approved the protocol and informed written consent was obtained from all subjects . whole brain anatomical scans were recorded using a magnetization prepared rapid acquisition gradient echo sequence with the following parameters  tr : 2300  ms ; te : 2.98  ms ; flip angle : 9 ; 192 sagittal slices ; matrix : 256    256  mm ; bandwidth : 240  hz / px , voxel size : 1    1    11  mm  on a siemens tim trio scanner equipped with a 12-channel head coil . for the determination of body fat distribution ( i.e. vat ) a standardized measurement protocol an axial t1-weighted fast spin echo sequence with a train length of 7 was applied ( tr : 490  ms , te : 12  ms , slice thickness : 10  mm with 10  mm gap between slices , field of view : 430530  mm , matrix size : 256    178 ) on a 1.5 tesla siemens scanner ( magnetom sonata , siemens healthcare , erlangen , germany ) . cortical thickness analysis was performed using freesurfer software package ( v5.10 ) ( http://surfer.nmr.mgh.harvard.edu ) . standard preprocessing of the structural images was performed including intensity normalization , talairach transformation , skull stripping , white matter segmentation , and tessellation and inflation of the surface ( dale et al . , 1999 ) . the pial surface of each hemisphere was computed by using a deformable surface algorithm to extract white matter surface outward toward the gray matter boundary . after automatic correction of topological defects ( fischl et al . , 2001 ) , each individual image was visually checked for labeling inaccuracies in white matter and pial surface . in case of defective labels the distance between the white matter surface and pial surface yields an estimate of cortical thickness at each vertex ( fischl and dale , 2000 ) . for further analysis the data was transformed into a common template with a smoothing kernel of 10  mm which is in line with most cortical thickness studies . higher smoothing kernels ( 20  mm and above ) as suggested by other groups ( lerch and evans , 2005 ) were not used to minimize artificial extension of cortical thinning patterns ( bernal - rusiel et al . , 2010 ) . whole body image analysis was performed with customized matlab ( mathworks , natick , ma ) scripts . volumetric assessment of different adipose tissues was based on intensity threshold values separating visceral adipose tissue ( vat ) and abdominal subcutaneous tissue . the respective selected pixels were multiplied with the in - plane pixel dimensions and slice thickness and the resulting volumes were calculated in liters ( machann et al . , 2005 ) . to compute differences in cortical thickness vertex - by - vertex analyses were performed separately for each hemisphere . in a first step , we defined two different general linear models ( glms ) using vat or bmi respectively as predictors ( continuous variable ) . we defined in both models sex ( discrete variable ) , age and educational status as confounding variables . educational level was coded on a discrete scale with three levels ( middle school , high school , academics ) . to account for possible head size effects both variables were non - normally distributed and were logarithmically transformed prior to glm analysis . furthermore , we tested whether the slope for males and females were different regarding the continuous variables . we found no gender specific slopes and used a model with one regressor for each covariate . to evaluate the specific contribution of each predictor to the changes in cortical thickness we defined a model with vat and bmi as regressors , while age , sex , total surface area and education were kept as confounds . all continuous variables were mean centered . the results were corrected for multiple comparisons over both hemispheres using a monte carlo simulation to assign clusters surviving a cluster - wise significance threshold of p  <  0.05 . in addition to the vertex - wise analysis , we labeled the significant clusters and calculated the average cortical thickness of the vertices within each labeled cluster separately for each subject . linear regression analyses were performed using the cluster - wise averaged thickness values as dependent variable . additionally , we computed a partial correlation analysis with bmi , age , sex and educational status as control variables and vat as dependent variable . the multiple regression analyses revealed that increasing bmi was associated with decreased cortical thickness in a cluster extending from the right precentral gyrus to the postcentral gyrus , the insula and the pars triangularis and pars opercularis . in the left hemisphere , there were two clusters with cortical thinning namely in the inferior temporal and the inferior parietal cortex ( the clusters include also the middle temporal , lateral occipital and fusiform areas ) ( fig . 1 ; table 2 ) . increasing vat was significantly related to cortical thinning in a cluster centered around the left fusiform gyrus extending into the inferior parietal , the inferior temporal and the lateral occipital cortex . in the right hemisphere , we found a significant reduction of cortical thickness in a cluster including the insula ( extending into the precentral and postcentral gyrus ) and a second cluster in the inferior temporal cortex including the fusiform gyrus ( fig . 2 ; table 2 ) . the glm analysis using vat and bmi as predictors revealed a vat specific reduction ( adjusted for bmi ) in cortical thickness in a cluster including the transverse temporal gyrus , the superior temporal gyrus and the mid - insula ( fig . partial correlation analysis using the average cortical thickness in the labeled cluster of the transverse temporal gyrus confirmed the unique contribution of vat ( adjusted for bmi ) for the reduced cortical thickness . no significant correlations were found between bmi or vat and global values of surface area and average cortical thickness . the present study aimed to investigate the relationship between visceral adipose tissue and bmi on changes in cortical thickness in a group of lean , overweight and obese young to middle - aged adults . in agreement with recent volumetric studies , reduced gray matter thickness was associated with both increased bmi and increased vat in lateral occipital areas ( e.g. fusiform gyrus ) ( karlsson et al . , 2013 ; pannacciulli et al . , 2006 ; recent research has identified the fusiform gyrus as an important structure for discriminating high from low caloric food cues ( van der laan et al . , 2011 ) . of note , overweight / obese subjects showed decreased activation in the fusiform gyrus to food items compared to lean subjects ( kullmann et al . , 2013 ) . on the other hand , in the current study , we observed more extended reductions in the right inferior temporal gyrus and the insula in relation to vat but not bmi . however , there is large overlap of areas with significant reductions in relation to vat and bmi , which is mainly due to the relative high correlation between both variables . even independent of bmi , we were able to show that increasing vat was related to reduced cortical thickness mainly in the temporal cortex and the mid - insular region . concomitantly , volumetric reductions in gray matter volume of temporal areas have been repeatedly shown in obese adults ( karlsson et al . , 2013 ; kurth et al . , 2013 ; weise et al . , 2013 ) . interestingly , in type 2 diabetes patients reduced cortical thickness was also identified in the medial temporal cortex ( brundel et al . , 2010 ) . considering the fact that the risk of developing obesity related diseases , such as type 2 diabetes and metabolic syndrome , is strongly related to abdominal adiposity , a possible pathomechanism underlying the relationship between cortical thinning and increasing vat may arise from inflammatory responses . these are seen in connection with adipose tissue in obesity ( karlsson et al . , 2013 ) . ( 2013 ) showed that vat is only related to c - reactive protein ( crp ) compared to other inflammatory markers . crp is an important marker of infection or inflammation and crp levels are often elevated in obese subjects ( choi et al . , 2013 ) , in particular in individuals with metabolic syndrome ( aronson et al . , 2004 ) . in the present sample , there was a significant difference between overweight / obese compared to lean subjects in relation to crp levels . increased crp levels are markers of cardiovascular disease risk and current evidence suggests impaired microstructural integrity in relation to elevated crp levels ( wersching et al . , 2010 ) . ( 2013 ) investigated the association between crp and regional gray matter differences in a healthy elderly cohort . the authors found volumetric reductions in a strictly defined area in the left lateral temporal cortex almost exactly located in a region that we found in the present study . although a causal linkage between crp levels and gray matter reductions is difficult to establish , there is evidence that atherosclerosis affects cerebral blood flow regulatory processes ( nobili et al . , 1993 ) in a way that ischemic states can occur more often and lead to tissue degeneration . moreover , increased cardiovascular risk factors are associated with reduced cortical thickness in temporal and parietal areas ( cardenas et al . , 2012 ) . the gray matter loss in the left temporal cortex can be an early indicator of low grade inflammatory processes that lead to tissue degeneration . in this study we found cortical thinning in relation to bmi and vat in a group of young to middle - aged adults . with increasing visceral adipose tissue , we identified extended cortical thinning in the left temporal cortex independent of bmi . since vat is strongly related to cardiac and metabolic risk factors , a possible mechanism may arise from adipose tissue related low grade inflammation processes as a potential harmful factor on brain integrity , although the exact mechanisms including hormonal , metabolic and lifestyle factors underlying structural changes warrant further investigations .
structural brain imaging studies have shown that obesity is associated with widespread reductions in gray matter ( gm ) volume . 
 although the body mass index ( bmi ) is an easily accessible anthropometric measure , substantial health problems are more related to specific body fat compartments , like visceral adipose tissue ( vat ) . 
 we investigated cortical thickness measures in a group of 72 healthy subjects ( bmi range 2035  kg / m2 , age range 1950  years ) . 
 multiple regression analyses were performed using vat and bmi as predictors and age , gender , total surface area and education as confounds . 
 bmi and vat were independently associated with reductions in cortical thickness in clusters comprising the left lateral occipital area , the left inferior temporal cortex , and the left precentral and inferior parietal area , while the right insula , the left fusiform gyrus and the right inferior temporal area showed a negative correlation with vat only . 
 in addition , we could show significant reductions in cortical thickness with increasing vat adjusted for bmi in the left temporal cortex . 
 we were able to detect widespread cortical thinning in a young to middle - aged population related to bmi and vat ; these findings show close resemblance to studies focusing on gm volume differences in diabetic patients . 
 this may point to the influence of vat related adverse effects , like low - grade inflammation , as a potentially harmful factor on brain integrity already in individuals at risk of developing diabetes , metabolic syndromes and arteriosclerosis .