TY - JOUR T1 - The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the “obesity paradox” A1 - Ito, Ryuichi A1 - Narita, Shintaro A1 - Huang, Mingguo A1 - Nara, Taketoshi A1 - Numakura, Kazuyuki A1 - Takayama, Koichiro A1 - Tsuruta, Hiroshi A1 - Maeno, Atsushi A1 - Saito, Mitsuru A1 - Inoue, Takamitsu A1 - Tsuchiya, Norihiko A1 - Satoh, Shigeru A1 - Habuchi, Tomonori Y1 - 2017/02/08 N2 - Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this “obesity paradox” is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin. Overweight and obese patients had significantly lower grade cancers than normal patients in all patients and in those without metastasis (p = 0.003 and p = 0.027, respectively). Cancer-specific survival was significantly longer in overweight and obese patients than in normal patients in all patients (p = 0.035). There was a weak inverse correlation between sAd level and BMI in RCC patients (r = −0.344, p = 0.002). Tumor size was slightly correlated with sAd level, and high sAd was significantly associated with poor overall survival rates in patients with non-metastatic RCC (p = 0.035). Adiponectin levels in perinephric adipose tissue and intratumoral AdipoR1/R2 expression were not correlated with RCC aggressiveness or survival. Proliferation significantly increased in 786-O and Caki-2 cells exposed to exogenous adiponectin, whereas cell invasion and migration were unaffected. In addition, exogenous adiponectin significantly inhibited starvation- and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels. In summary, low BMI and high adiponectin levels are associated with aggressive cell behaviors and poor survival in surgically-treated RCC patients. The effects of adiponectin on proliferation and apoptosis might underlie the “obesity paradox” of RCC. JF - PLOS ONE JA - PLOS ONE VL - 12 IS - 2 UR - https://doi.org/10.1371/journal.pone.0171615 SP - e0171615 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pone.0171615 ER -