The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox".
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.
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
Ryuichi
R
Ito
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.|AMED-CREST, Japan Agency for Medical Research and Development.
Shintaro
S
Narita
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.|AMED-CREST, Japan Agency for Medical Research and Development.
Mingguo
M
Huang
Department of Urology, Yamagata University Graduate School of Medicine, Yamagata, Japan.
Taketoshi
T
Nara
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
Kazuyuki
K
Numakura
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
Koichiro
K
Takayama
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
Hiroshi
H
Tsuruta
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
Atsushi
A
Maeno
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
Mitsuru
M
Saito
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.|AMED-CREST, Japan Agency for Medical Research and Development.
Takamitsu
T
Inoue
Department of Urology, Yamagata University Graduate School of Medicine, Yamagata, Japan.
Norihiko
N
Tsuchiya
Center for Kidney Disease and Transplantation, Akita University Hospital, Akita, Japan.
Shigeru
S
Satoh
Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.|AMED-CREST, Japan Agency for Medical Research and Development.
Tomonori
T
Habuchi
D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015415:Biomarkers; D015992:Body Mass Index; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009765:Obesity / Q000150:complications* / Q000378:metabolism*; D063868:Patient Outcome Assessment; D015398:Signal Transduction; D016019:Survival Analysis; D055815:Young Adult
D052242:Adiponectin; D015415:Biomarkers