Adipose tissue measurement in clinical research for obesity, type 2 diabetes and NAFLD/NASH

Abstract

Introduction:Excess body fat is linked to higher risks for metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CV), among other health conditions. However, it is not only the level but also the distribution of body fat that contributes to increased disease risks. For example, an increased level of abdominal fat, or visceral adipose tissue (VAT), is associated with a higher risk of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).Methods: A review of the most relevant primary and secondary sources on body composition from the last 25 years was conducted. Relevant articles were identified using PUBMED and Google Scholar. Narrative synthesis was performed as statistical pooling was not possible due to the heterogeneous nature of the studies. Results:The body mass index (BMI) is commonly used as a proxy measure of body fatness. However, BMI does not reflect the level and distribution of body fat. Other anthropometric methods such as waist circumference measurement and waist-hip ratio, as well as methodologies like hydro densitometry, bioelectrical impedance, and isotope dilution are also limited in their ability to determine body fat distribution.Imaging techniques to define body composition have greatly improved performance over traditional approaches. Ultrasound (US), computed tomography (CT), dualenergy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), are now commonly used in clinical research. Of these, MRI can provide the most accurate and high-resolution measure of body composition. In addition, MRI techniques are considered the best for the determination of fat at the organ level. On the other hand, imaging modalities require specialized, often expensive equipment and expert operation.Conclusions: Anthropometric methods are suitable for rapid, high-volume screening of subjects but do not provide information on body fat distribution. Imaging techniques are more accurate but are expensive and do not lend themselves for high throughput. Therefore, successful trial strategies require a tiered approach in which subjects are first screened using anthropometric methods followed by more sophisticated modalities during the execution of the trial.

Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage

“…Of interest, in addition to transaminases, among the indices of liver steatosis and fibrosis included in our study population with visceral obesity, FIB4 and APRI were in the normal range, whereas FLI was higher than the normal values in practically all the patients. Adipocyte dysfunction is considered a key molecular link between visceral adipose tissue, MetS, and NAFLD [ 16 ], and larger deposits of visceral adipose tissue have proven to increase the 4-year risk of progression of incident NAFLD [ 17 ] and its progression to NASH [ 18 ]. Among the path ogenic mechanisms of NAFLD/NASH, visceral obesity might play a direct role in increasing the release of cytokines and other inflammatory mediators [ 19 ], or through the establishment of insulin resistance, might be an important factor in promoting the accrual of lipid droplets containing triglycerides, cholesterol esters, and other lipid species in the hepatocytes [ 20 ].…”

From an Apple to a Pear: Moving Fat around for Reversing Insulin Resistance

“…The BMI includes total body weight and is being used as a parameter in clinics, but it has limitations in accurately representing the complexity of obesity and other health complications [ 21 ]. A more precise way to assess excess fat storage would be to measure fat content in different depots [ 22 ]. The association between these depots and metabolic disorders will be discussed in detail in the next section.…”

Non-invasive biomarkers for liver inflammation in non-alcoholic fatty liver disease: present and future

“…A healthy liver will appear brighter (i.e., parenchymal hyperdensity) than the spleen in a CT scan. As fat content in the liver increases, its corresponding image will become darker (i.e., parenchymal hypodensity) [ 37 ]. CT liver images may be confounded by other factors such as concentration of iron, glycogen, and hematocrit.…”