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The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox".

ABSTRACT: 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.

SUBMITTER: Ito R

PROVIDER: S-EPMC5298294 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox".

Ito Ryuichi R Narita Shintaro S Huang Mingguo M Nara Taketoshi T Numakura Kazuyuki K Takayama Koichiro K Tsuruta Hiroshi H Maeno Atsushi A Saito Mitsuru M Inoue Takamitsu T Tsuchiya Norihiko N Satoh Shigeru S Habuchi Tomonori T

PloS one 20170208 2

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 agg ...[more]

PMID: 28178338

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Project description:BackgroundA high body mass index (BMI) has been associated with decreased mortality in critically ill patients. This association may, in part, relate to the impact of BMI on glycemia. We aimed to study the relationship between BMI, glycemia and hospital mortality.MethodsWe included all patients with a recorded BMI from four large international clinical databases (n = 259,177). We investigated the unadjusted association of BMI with average glucose levels, mortality and hypoglycemia rate. We applied multivariate analysis to investigate the impact of BMI on hypoglycemia rate, after adjusting for glycemia-relevant treatments (insulin, dextrose, corticosteroids, enteral and parenteral nutrition) and key physiological parameters (previous blood glucose level, blood lactate, shock state, SOFA score).ResultsWe analyzed 5,544,366 glucose measurements. On unadjusted analysis, increasing BMI was associated with increasing glucose levels (average increase of 5 and 10 mg/dL for the 25-30, 30-35 kg/m2 BMI groups compared to normal BMI (18.5-25 kg/m2) patients). Despite greater hyperglycemia, increasing BMI was associated with lower hospital mortality (average decrease of 2% and 3.25% for the 25-30, 30-35 kg/m2 groups compared to normal BMI patients) and lower hypoglycemia rate (average decrease of 2.5% and 3.5% for the 25-30, 30-35 kg/m2 groups compared to normal BMI patients). Increasing BMI was significantly independently associated with reduced hypoglycemia rate, with odds ratio (OR) 0.72 and 0.65, respectively (95% CIs 0.67-0.77 and 0.60-0.71, both p < 0.001) when compared with normal BMI. Low BMI patients showed greater hypoglycemia rate, with OR 1.6 (CI 1.43-1.79, p < 0.001). The association of high BMI and decreased mortality did not apply to diabetic patients. Although diabetic patients had higher rates of hypoglycemia overall and higher glucose variability (p < 0.001), they also had a reduced risk of hypoglycemia with higher BMI levels (p < 0.001).ConclusionsIncreasing BMI is independently associated with decreased risk of hypoglycemia. It is also associated with increasing hyperglycemia and yet with lower mortality. Lower risk of hypoglycemia might contribute to decreased mortality and might partly explain the obesity paradox. These associations, however, were markedly modified by the presence of diabetes.

Dataset Information

The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox".

Publications

The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox".

Similar Datasets

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