Body fat distribution: a crucial target for intervention in nonalcoholic fatty liver disease and fibrosis

Abstract

HepatoBiliary Surg Nutr 2022;11(5):738-742 | https://dx. Over the past decades, obesity has become an epidemic worldwide. Obesity impacts health burdens heterogeneously by the regional distribution of fat, not total body fat quantity. Epidemiologic studies reported that regional body fat distribution could represent a significant risk factor for insulin resistance (1), type 2 diabetes mellitus, and cardiovascular disease (2). Nonalcoholic fatty liver disease (NAFLD) affects approximately a fourth of the population worldwide and has been linked with overweight/ obesity. However, NAFLD can be seen in individuals without overweight/obesity, which is called lean NAFLD. It has been shown that in terms of body fat distribution, visceral adipose tissue (VAT) has a stronger association with NAFLD and severity in NAFLD than subcutaneous adipose tissue (SAT) (3-6). Total body fat quantity, as assessed by body mass index (BMI), does not reflect regional body fat distribution (7). Although waist circumference is a relatively accurate measurement to assess abdominal obesity, it does not represent body fat distribution because it is unable to distinguish VAT from SAT (8,9). A study demonstrated a strong correlation between sagittal abdominal diameter and VAT, whereas waist circumference was correlated with SAT more than VAT (10). Thus, BMI and waist circumference may be imperfect measurements to determine body fat distribution and risk stratification for individuals with NAFLD. We summarized studies that investigated the association between body fat distribution and NAFLD and the severity of NAFLD in Table 1 (3-5,11-14). A Korean study revealed that VAT area is the independent risk factor for elevated alanine aminotransferase (ALT) among individuals with NAFLD in both men [odds ratio (OR) =2.36; 95% confidence interval (CI): 1.48-3.76 comparing higher VAT quartile vs. lower VAT quantile; P for trend <0.001] and women (OR =3.70; 95% CI: 1.52-8.99; P for trend <0.001) independent of BMI and SAT area (5). In terms of the severity of NAFLD, a pilot study showed that VAT area might be dose-dependently linked with liver inflammation and fibrosis independent of insulin resistance (11). A subsequent study based on 456 histology-confirmed NAFLD and control demonstrated that VAT area was independently associated with nonalcoholic steatohepatitis (NASH) (OR =1.17; 95% CI: 1.05-1.32 per 10 cm 2 increase of VAT area) and significant fibrosis (F2-F4) (OR =1.21; 95% CI: 1.07-1.37 per 10 cm 2 increase of VAT area) (4). The earlier studies were mainly cross-sectional and could not draw the causal relationship between VAT and NAFLD. A cohort study (n=2,017) investigated the longitudinal association between body fat distribution and NAFLD incidence/ regression (3).