LAUSR

An increasing body of evidence has demonstrated that a remarkable number of cancers worldwide are associated with increased prevalence of obesity and metabolic derangements. Globally, it was estimated that 481 000 or 3.6% of all new cancer cases in adults greater than 30 years were attributable to a high body mass index (BMI). Among them, corpus uteri, postmenopausal breast, and colorectal cancer (CRC) accounted for 64% of cancers attributable to high BMI. Sedentary lifestyle with decreased physical activity and Westernized dietary habits with increased calorie intake and red meat consumption have been well established as the risk factors of CRC. These risk factors are collectively closely associated with the development of metabolic derangements, the so-called metabolic syndrome (MetS). The term MetS is a status of metabolic dysregulation characterized by insulin resistance with increased fasting glucose, hyperinsulinemia, low-grade inflammation, and a predisposition to type 2 diabetes and dyslipidemia (hypertriglyceridemia and low high-density lipoprotein cholesterol), and it has been correlated not only with premature atherosclerosis and resultant cardiovascular events but also with some cancers including CRC. Its occurrence is largely affected by the presence of visceral obesity or visceral adipose tissue (VAT) and is influenced by hormonal factors as well. It is important, as increased BMI may not consistently correlate with such risks, and several previous studies have demonstrated that the accumulation of fat in organs like the skeletal muscle and liver might be strongly associated with MetS, whereas subcutaneous fat might be protective. In this regard, body fat distribution, especially those accumulated in the visceral organs, is responsible for the MetS cluster and is clinically more relevant than the subcutaneous fat, by which the clinical significance of BMI is frequently confounded. The role of VAT in the pathogenesis of metabolic-associated disorder provided new insight in elucidating the linkage of obesity and related health outcomes, as obesity is a remarkably heterogeneous condition, and not every patient with obesity is featured by comorbidities and presented with MetS. It has become evident that the accumulation of VAT not only accompanies but also antedates the onset of the components of the MetS and its related disorders. In the overweight or obese subjects, a dangerous feedback loop may develop: increased VAT causes chronic low-grade inflammation, which in turn leads to increased insulin resistance rendering further VAT accumulation and increased susceptibility to disease. It was also demonstrated that not only the baseline colonoscopic finding but also the presence of MetS was associated with the risk of incident or metachronous advanced colorectal neoplasm after a negative colonoscopy or polypectomy for adenoma, showing its clinical significance in colorectal tumorigenesis. In this issue of Journal of Gastroenterology and Hepatology, Moon and colleagues reported that increasing changes in VAT area were longitudinally associated with a higher risk of incident and recurrent colorectal adenoma, with 35% increased risk for every 10-cm increment in VAT but not by the change in subcutaneous adipose tissue. The clinical significance of VAT on the risk of colorectal neoplasm was reported previously. According to the cross-sectional study by Nam et al., which investigated 3922 subjects who concurrently underwent colonoscopy and CT scan, it was demonstrated that increased VAT was associated with increased risk of colorectal adenoma, with 33% and 43% increased risk of adenoma for those with VAT volume of 1000–1499 and 1500 cm or greater, respectively, if compared with those with VAT less than 500 cm. It was also demonstrated that a high volume of VAT was also positively associated with larger (>10 mm) and multiple adenomas. The finding from the current study is even more clinically relevant, as it provides the longitudinal effect of VAT change on the risk of subsequent risk of colorectal adenoma, which paves the way for future primary prevention for CRC. Because VAT could be reduced via lifestyle modification (decreased calorie intake or vigorous exercise), which is independent of BMI, therefore such finding implies that many chronic diseases, including CRC, could be effectively prevented via lifestyle intervention. A previous study by Kim et al. demonstrated that metabolically unhealthy nonobese subjects had a significantly higher risk of metachronous colorectal neoplasm than that in the metabolically healthy obese subjects. The finding of the current study by Moon and colleagues concurrently explains why VAT rather than subcutaneous plays the central role in colorectal tumorigenesis and why metabolic derangement rather than obesity or BMI could explain the increased risk of metachronous neoplasm. Several issues are worthwhile for further exploration regarding this study. Firstly, in the current study, metachronous adenoma rather than advanced adenoma was used as the outcome measurement. Because advanced adenoma is a better proxy of invasive cancer than adenoma as a whole and using it is clinically more relevant. Second, there remains lacking a feasible way of regular measurement of VAT. The techniques for measuring visceral adiposity vary in accessibility, specificity, and accuracy in quantifying VAT. Though computer tomography is the standard way of measuring VAT with high accuracy, radiological exposure is a significant concern. MRI also shows very high specificity, accuracy, and reproducibility in measuring VAT, but it is more costly and may not be accessible in small centers. Though without radiation exposure and more accessible, the major concern of using ultrasonography in measuring VAT is its operator-dependent character and resultant low reliability. Development of a new system accommodating modality with lower radiological exposure, anthropometric measurements, and other clinical demographics that has a good correlation with VAT is warranted for its future application for lifestyle intervention. Finally, the gut microbiota is now widely recognized as an important factor contributing to the regulation of host metabolic functions and adiposity. Whether modulation of gut microbiota via probiotics or other lifestyle intervention can help to regulate metabolic cross-talk communication between the gut doi:10.1111/jgh.15584