Nafld: a Multisystem Disease

Several epidemiological studies show that obesity and related metabolic dysfunctions are associated with an increased incidence and mortality rates for various types of tumors. For example, it has been shown that obesity and type 2 diabetes are among the risk factors associated with the onset of colon cancer.

Among the new emerging risk factors for the onset of extra-hepatic tumors, NAFLD has played an important role in the development of tumors of the gastro-intestinal tract. In addition NAFLD is strongly associated with features of the metabolic syndrome, including obesity, insulin resistance, type 2 diabetes mellitus (DM2) and dyslipidemia.

It is known that among the risk factors for the onset of NAFLD there are the bad eating habits associated with a sedentary lifestyle, in this case a combination of dietary restrictions associated with physical activity is commonly recommended for people with NAFLD. However, a significant proportion of patients develop NAFLD despite having a normal body mass index (BMI) and some features of the metabolic syndrome.

Today lifestyles are increasingly sedentary, and NAFLD has quickly become one of the most common causes of liver disease worldwide. NAFLD is a condition closely related to obesity, diabetes and metabolic syndrome. It is often diagnosed following an occasional ultrasound evaluation of the abdomen, but in reality many cases are associated with other metabolic disorders (hypertriglyceridaemia, hypercholesterolemia, hypertension), configuring the panel of the so-called "metabolic syndrome".

Visceral obesity is an important risk factor in the onset of NAFLD. In fact, the prevalence of NAFLD increases with the increase in body mass index (BMI). An accumulation of ectopic fat, including visceral obesity and fatty liver, can lead to adipose tissue dysfunction with consequent alteration of adipocytokine levels. One of the key factors in the pathogenesis of NAFLD is determined by insulin resistance (IR) (Figure 1), NAFLD is therefore considered the hepatic component of the metabolic syndrome (SM) or IR. The state of chronic low-grade inflammation due to obesity and the presence of NAFLD leads to the emergence of a micro-environment favorable to the development of cancer and the onset of insulin resistance due to activation of the axis that regulates the insulin growth factor-1 IGF-1 and insulin resulting in hyperinsulinemia. Through its proliferative and anti-apoptotic effects, this process can increase mutations that promote carcinogenesis. NAFLD is now considered the liver manifestation of the metabolic syndrome (MS) and the latter, as shown by numerous studies, represents a condition that increases the risk of cancer, especially in the gastrointestinal tract. Colorectal cancer (CRC) has so far been consistently associated with NAFLD. The mechanisms that associate NAFLD with the risk of developing cancer are still not fully known, but they probably derive from the two-way relationship between NAFLD and the metabolic syndrome. NAFLD and visceral adipose tissue represent the main parts of the axis of central obesity.