| ObjectiveObesity is related to the incidence and development of colorectal cancer (colorectal cancer, CRC). A variety of evidence showed that dysfunction of adipose tissue may be involved in the development of CRC. Adipokines, secreted from adipose tissue, may regulate appetite, food intake, energy metabolism, insulin sensitivity, inflammation, angiogenesis, and cell growth and apoptosis. Adipokines may be one of in mechanisms of obesity-related CRC. Adiponectin, involved in insulin sensitivity, had a significant lower level in the serum of CRC patients. Leptin is primarily involved in food intake and energy expenditure. Serum Leptin level was increased in obese population. Elevated serum Leptin level was an independent risk factor for CRC. However, there is a lack of clinical evidence of correlation of new adipokines with CRC, such as Zinc-a2-glycoprotein (ZAG), activating transcription factor3(ATF3), and fibroblast growth factor21(FGF21), which were mainly involved in insulin sensitivity; as well as Ghrelin, Irisin and glucagon-like peptide-1(GLP-1), which were primarily involved in energy expenditure.We design this research to preliminary explore expressions of the adipokines mentioned above in normal-weight and overweight/obese patients with CRC.MethodsSeventy-nine CRC patients having surgery at the Department of General Surgery of Peking Union Medical College Hospital from June,2012to April,2014were selected. They were pathologically confirmed to having colon/rectal cancer. According to BMI, the patients were divided into group of NW+CRC(18Kg/m2<BMI<25Kg/m2, n=44), and group of OW/OB+CRC(BMI>25Kg/m2, n=40).40healthy subjects were enrolled in the normal control group (18Kg/m2<BMI<25Kg/m2, n=35).ELISA method was applied to detect levels of high molecular weight (high molecular weight, HMW)-adiponectin, ZAG, TNF-a, ATF3and FGF21), which were mainly related to fat and insulin sensitivity factor, as well as Leptin, Irisin, Ghrelin and GLP1, which were mainly related to energy expenditure.Adipokines mRNA were determined in visceral adipose tissue and subcutaneous adipose tissue in9normal-weight CRC patients (18Kg/m2<BMI<25Kg/m2) and9obese CRC patients (BMI≥30Kg/m2).Results1. Serum adipokine levels in normal weight, overweight/obesity patients with CRC patients1) Compared with normal controls, serum ZAG level was increased by13%(1.50±0.04vs1.33±0.04, P-0.003) in normal-weight CRC patients. Compared with normal controls, serum ATF3level was increased by51%(0.65±0.04vs0.43±0.02, P=0.003) in overweight/obese CRC patients, and also increased by37%(0.59±0.04vs0.43±0.02, P <0.001) in normal-weight CRC patients.2) Compared with normal-weight CRC patients, serum Leptin level was increased by58%(2.87±0.26vs1.82±0.30, P=0.002) in overweight/obese CRC patients; Compared with normal controls, serum Irisin level was decreased by23%(0.168±0.014vs0.219±0.013, P<0.001) in normal-weight CRC patients.3) Among77cases of male subjects, compared with normal-weight CRC male patients, serum HMW-adiponectin level was decreased by38%(1.67±0.24vs2.68±0.27, P=0.009) in overweight/obese CRC male patients; serum Leptin level was increased by85%(2.22±0.30vsl.20±0.26, P=0.002). Compared with normal healthy males, serum ZAG level was increased by19%(1.52±0.053vs1.28±0.046, P=0.001) in normal-weight CRC male patients, and also increased by20%(1.53±0.059vs1.28±0.046, P=0.002) in overweight/obese male CRC patients.4) Correlation analysisa) Among CRC patients, serum HMW-adiponectin levels were negatively related to BMI (r=-0.279, P=0.016) and serum TG levels(r=-0.287, P=0.015). After being adjusted for the age and gender, the correlation was still significant(r=-0.275, P=0.018;). Serum HMW-adiponectin and TG levels were positively correlated (r=0.343, P=0.003). After being adjusted for the age, gender and BMI, the correlation was still significant(r=-0.240, P=0.047);b) Serum Leptin levels were positively related to BMI (r=0.360, P=0.002). After being adjusted for the age and gender, the correlation was still significant (r=0.364, P=0.002). Serum Leptin and TG levels were positively correlated (r=0.343, P=0.003). After being adjusted for the age, gender and BMI, the correlation was still significant (r=0.278, P=0.022).c) Serum Irisin levels were positively related to serum TG levels (r=0.322, P=0.006). After being adjusted for the age, gender and BMI, the correlation was still significant (r=0.254, P=0.035).2. Expression of adipokines mRNA in adipose tissue in normal-weight, overweight and obese CRC patientsCompared with normal-weight CRC patients, expression of TNF-a mRNA in visceral adipose tissues was increased by5.13fold (613.05±4.03vs100.00±2.21, P=0.006) in obese CRC patients. While expression of AZGP1mRNA in subcutaneous adipose tissues was decreased by70%(30.41±1.98vs100.00±2.16, P=0.002).Conclusions1. Among CRC patients, serum Adiponectin levels were negatively related to BMI, while serum Leptin levels was positively related to BMI, and the difference was more significant among male patients.2. Compared with normal-weight CRC patients, expression of TNF-a mRNA in visceral adipose tissues was significantly higher in obese CRC patients.3. Compared with normal weight healthy subjects, serum ZAG levels were significantly increased in normal-weight CRC patients and overweight/obese CRC patients. While compared with normal-weight CRC patients, expression of AZGP1mRNA in subcutaneous adipose tissues was significantly decreased in obese CRC patients.4. Compared with normal weight healthy subjects, serum Irisin level was significantly increased in normal-weight CRC patients.5. Compared with normal weight healthy subjects, serumATF3levels were significantly increased in normal-weight CRC patients and overweight/obese CRC patients..
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