Adiponectin Signaling May Explain “Obesity Paradox” of RCC

Body mass index (BMI) was inversely correlated with serum adiponectin levels in renal cell carcinoma (RCC), and low BMI and high adiponectin might be associated with disease aggressiveness and survival in patients with the disease, according to the results of a recent study.

Ryuichi Ito, department of urology, Akita University Graduate School of Medicine, Japan, and colleagues wrote in PLoS One, that “interpretation of the results was complicated and we cannot extrapolate these results to clinical practice,” but “insight into the ‘obesity paradox’ can help facilitate the development of precision medicine and novel therapeutics for RCC.”

The “obesity paradox” in RCC is that obesity has been shown to increase the risk for RCC, but obese patients with the disease have longer survival than non-obese patients. With this study, Ito and colleagues wanted to assess the effects of obesity and adiponectin signaling on outcomes of patients with surgically treated RCC.

They assessed preoperative BMI, serum total adiponectin level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors and their possible effect on the aggressiveness of RCC and survival from the disease. Serum and tissue samples were taken from 129 patients with RCC who underwent kidney surgery between 2005 and 2011 at Akita University Hospital. Median BMI was 23.1 kg/m²; 25.6% of patients were overweight and 6.2% were obese.

Results showed that patients considered overweight or obese were diagnosed with significantly lower grade cancers than normal weight patients. In addition, overweight and obese patients had significantly longer cancer-specific survival (CSS) compared with normal weight patients (5-year CSS: 96.9% vs 75%; P = .039).

Looking at the markers for obesity, the researchers found only a weak inverse association between serum total adiponectin and BMI (P = .002). Mean serum total adiponectin level was significantly greater in patient with tumors of 4 cm or greater than in patients with tumors less than 4 cm (P = .001).

High serum adiponectin levels were significantly associated with poor overall survival rates in patients with non-metastatic disease (P = .035). No association was found between RCC aggressiveness or survival and the adiponectin levels in perinephric adipose tissue and intratumoral expression of adiponectin receptors.

The researchers also examined possible mechanisms underlying adiponectin-enhanced cancer aggressiveness by conducting in vitro functional analyses using RCC cell lines. They found that 786-O and Caki-2 cells exposed to exogenous adiponectin significantly increased proliferation, but cell invasion and migration were unaffected. Exogenous adiponectin also significantly inhibited starvation- and metformin-induced cell death, and upregulated p-AMPK and Bcl-xL levels.