Authorities give emphasis on various facts: j) the prevalence of obesity is increasing worldwide, especially in the young adult population; jj) obesity is characterized by a state of low-grade chronic inflammation at all ages; jjj) although VAT is more highly correlated with metabolic risk factors even after accounting for standard anthropometric indexes, it is possible that SAAT actually contributes a more absolute risk because SAAT volume is greater than VAT ; jjjj) in adults, visceral fat is directly associated with liver inflammation and fibrosis independently of insulin resistance and HS and it should be a central target for future interventions in NAFLD and indeed in all the metabolic diseases . On the other hand, a recent observation has highlighted the role of spleen as further non invasive marker of chronic low-grade inflammation in "dysmetabolic" patients with obesity and/or visceral adiposity .
Commenting on the results, we can observe that our data in young obese patients do not support an association between anthropometric measurements and HOMA. HOMA was well correlated to severity of HS and to the spleen size, both evaluated at US. The HS score was different in the two groups, so the MS detection. The main inflammatory index (CRP) and SLD behaved like HOMA, suggesting a strict link between inflammatory status and IR, but not necessarily in this sequence. In other words, enhanced spleen size, HS presence and CRP levels represented a reliable tool in confirming IR. These findings add to the body of pertinent knowledge the concept that a partially "benign" obesity, characterized by absence of IR, lack of HS or at the most presence of "light" form, lower or normal serum levels of inflammatory markers and, in few cases, minimal elevation of aminotransferase can exist in this particular population, at least at the moment of study.
Discussing possible mechanisms and explanations for our findings, we can argue that IR presence is the most important factor in determining the fat deposition in organs (in our case liver) unrelated to BMI, visceral and subcutaneous abdominal adipose tissue stores. If IR has a genetic determinant or is a phenotypic expression, it remains to be established. Although it is generally thought that organ deposition starts occurring when visceral and subcutaneous abdominal adipose tissue stores are full, we were not able to confirm this point. Being IR not related to the entity of fat deposition, we hypothesize that the chain of events does not presuppose the obesity as if it was the cause of IR; this fact is supported by the clear association between the inflammatory status (CPR levels and spleen volume) and the HS score. Could the high fat liver content be the breaking point between "benign" and "progressive" obesity? This is the first intriguing question that could be answered in the course of successive follow-ups of this population, as work in progress. Comparing study results with relevant findings from other published work, we found a possible confirmation in a study that suggests that the contribution of visceral fat to inflammation may not be completely accounted for by clinical measures of obesity (BMI and WC, ). A second point of the problem to stress is whether the weight control can slow down the progression of IR and the worsening of fat deposition in organs in these obese young patients as for overweight subjects .
Furthermore, although insulin sensitivity was negatively correlated with liver fat content in overweight and moderately obese pre-pubertal children, inflammation markers were not correlated with insulin sensitivity , contrary to adults. This last aspect makes gain ground to the hypothesis that IR presence is associated with inflammation after many years and probably liver produces great amount of CRP to reacts to its continuous fat deposition. Having found in "dysmetabolic" patients a spleen volume increased strengthens this hypothesis and proposes this measurement as a non-invasive parameter to weigh the grass-roots low-grade chronic inflammatory process.
Discussing the limitations of the present study we have to pinpoint that liver biopsy is currently used to distinguish between 'simple' fatty liver and NASH, or stage the degree of fibrosis accurately, even though a recent study has demonstrated a good correlation between liver histology and US features . It is very likely that US will be very often used in clinical practice for the routine assessment of regional adiposity , although other methods are more specific; among these, magnetic resonance imaging is fairly well established , together with magnetic resonance spectroscopy . US imaging is also emerging as useful method for quantification of VAT, SAAT and tissue fat content in vivo for therapeutic interventions, i.e., when repeated measures are requested after diet programs. Any crucial future research directions should consider the reliability of this imaging tool.
The clinical implications summarized in a straightforward and circumspect manner of the work is that we believe that our data reinforce the need to start weight control at the "earliest possible time" in the progression of disease, i.e., obesity/MS, which means diagnosing NAFLD earlier, rather than later by the means of the simplest method possible, i.e., at US.