A hint for the obesity paradox and the link between obesity, perirenal adipose tissue and Renal Cell Carcinoma progression

Abstract

Increasing evidence supports a role for local fat depots in cancer outcomes. Despite the robust positive association of obesity with renal cell carcinoma (RCCa) diagnosis, increased adiposity is inversely related to RCCa oncological outcomes. Here, we sought to ascertain whether imagiologically assessed local fat depots associate with RCCa progression and survival and account for this apparent paradox. A retrospective cohort of renal carcinoma patients elective for nephrectomy (n = 137) were included. Beyond baseline clinicopathological characteristics, computed tomography (CT)-scans at the level of renal hilum evaluated areas and densities of different adipose tissue depots (perirenal, subcutaneous, visceral) and skeletal muscle (erector spinae, psoas and quadratus lumborum muscles) were analyzed. Univariate and multivariable Cox proportional hazards models were estimated following empirical analysis using stepwise Cox regression. Age, visceral adipose tissue (VAT) area and body mass index (BMI) predicted tumour-sided perirenal fat area (R-2 = 0.584), which presented upregulated UCP1 expression by 27-fold (P = 0.026) and smaller adipocyte areas, compared with subcutaneous depot. Multivariate analyses revealed that increased area of perirenal adipose tissue (PRAT) on the contralateral and tumour side associate with improved progression-free survival (HR = 0.3, 95CI = 0.1-0.8, P = 0.019) and overall survival (HR = 0.3, 95CI = 0.1-0.7, P = 0.009). PRAT measurements using CT, might become a possible tool, well correlated with other measures of obesity such as VAT and BMI, that will improve determination of obesity and contribute to assess the risk for disease progression and mortality in renal cancer patients. Present data supports the obesity paradox in RCCa, assumed that larger PRAT areas seem to protect from disease progression and death.