The inflammatory C-Reactive Protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, type 2 diabetes, and NASH

OBJECTIVE: C-Reactive Protein (CRP), a nonspecific marker of inflammation that is moderately elevated in obesity, metabolic syndrome (MS), and type 2 diabetes, has been proposed as a surrogate marker of nonalcoholic steatohepatitis (NASH). Its clinical usefulness in the diagnosis of NASH was evaluated in severely obese patients without or with MS, diabetes, and NASH and the potential roles of the liver and of the adipose tissue in CRP production were characterized. METHODS: Severely obese patients without NASH (without MS [N = 13], with MS [N = 11], or with MS and diabetes [N = 7]) and with NASH (without [N = 8] or with [N = 7] MS) were studied. For each patient, liver and adipose tissue biopsies were collected during a bariatric surgery and were used to determine the CRP gene expression by real-time PCR. The role of interleukin-6 (IL6) and lipopolysaccharide in CRP expression was also evaluated in subcutaneous adipose tissue obtained during cosmetic abdominoplasty. RESULTS: Plasma CRP levels were elevated in severely obese patients independently from the presence or absence of MS, diabetes, or NASH. CRP gene expression was not only increased in livers but also in adipose tissues of obese patients compared with controls subjects. In human adipose tissue, CRP mRNA levels were positively correlated with those of IL-6 and the CRP expression was enhanced in vitro by IL-6 and lipopolysaccharide. CONCLUSION: Plasma CRP levels are not predictive of the diagnosis of NASH in severely obese patients. The liver but also the adipose tissue can produce CRP, a process which could be dependent on IL6. Therefore, both tissues might contribute to the elevated plasma CRP levels found in obesity. In addition, the large amount of body fat may well produce an important part of the circulating CRP, further limiting its clinical usefulness in the evaluation of NASH in severely obese patients.