Macrophages and fibrosis in adipose tissue are linked to liver damage and metabolic risk in obese children

Abstract

Objective Obesity in childhood is associated with an inflammatory state in adipose tissue and liver, which elevates risk for diabetes and liver disease. No prior study has examined associations between pathologies occurring in adipose tissue and liver to identify elements of tissue damage associated with type 2 diabetes risk. This study sought to determine if inflammation and fibrosis in abdominal subcutaneous adipose tissue (SAT) in obese/overweight children (BMI-z 2.3±0.76) was related to the extent of observed liver disease or type 2 diabetes risk. Design & Methods Biopsy samples of abdominal (SAT) and liver were simultaneously collected from 33 Italian children (mean BMI 28.1±5.1 kg/m2 and mean age 11.6±2.2 years) with confirmed NAFLD. Histology and immunohistochemistry were conducted on biopsies to assess inflammation and fibrosis in adipose tissue and fibrosis and inflammation in liver. Results Presence vs. absence of crown like structures (CLS) in SAT was significantly related to liver fibrosis scores (1.7±0.7 vs. 1.2±0.7, p=0.04) independent of BMI. SAT fibrosis was significantly correlated with a lower disposition index (r=−0.48, p=0.006). No other adipose measures were associated with liver disease parameters. Conclusion Markers of subcutaneous WAT inflammation are associated with greater extent of liver fibrosis independent of obesity and SAT fibrosis may contribute to diabetes risk through reduced insulin secretion.

The Role of Tissue Macrophage-Mediated Inflammation on NAFLD Pathogenesis and Its Clinical Implications

“…These unique histological structures are correlated with hepatic inflammation and fibrosis [121]. Interestingly, in obese children with NAFLD, subcutaneous adipose tissue has CLS strictly correlated with liver fibrosis scores and diabetes risks [137]. …”

Comparison of the Phenotype and Approach to Pediatric vs Adult Patients With Nonalcoholic Fatty Liver Disease

“…37–39 A few clinical studies have suggested that the role of the gut microbiome and adipose tissue in inducing respectively endotoxemia and chronic systemic inflammation, and consequent liver tissue necro-inflammation, could be crucial for pediatric NAFLD as well as for the adult form of disease. 40–42 Over the past 5 years there has been a growing understanding of the role of gut microbiome in NAFLD pathogenesis. Notably, some difference have been shown in the gut microbiota composition that differ in children with NASH compared with healthy and obese subjects.…”

Early Glucose Derangement Detected by Continuous Glucose Monitoring and Progression of Liver Fibrosis in Nonalcoholic Fatty Liver Disease: An Independent Predictive Factor?

“…All biopsies were routinely processed (i.e., formalin fixed and paraffin embedded), and sections of the liver tissue were stained with hematoxylin and eosin, Van Gieson's stain, periodic acid-Schiff diastase, and Prussian blue stain. Steatosis, inflammation, hepatocyte ballooning, and fibrosis were all scored using the NAFLD Clinical Research Network (CRN) criteria [16]. Biopsies were evaluated by a single hepatopathologist who was blind to the clinical and laboratory data.…”

“…On the basis of OGTT data, subjects were categorized as presenting normal glucose tolerance (NGT; FPG <100 mg/dl, 2-hour postloaded glucose <140 mg/dl), IFG (FPG >100 and <126 mg/dl, 2-hour postloaded glucose <140 mg/dl), IGT (FPG <100 mg/dl, 2-hour postloaded glucose >140 and <200 mg/dl) or diabetes (FPG >126 mg/dl and/or 2-hour postloaded glucose >200 mg/dl) [16]. Based on reported MARD values for hyperglycemia, we defined three different CGM categories: diabetes, if two or more glucose random values, registered on 2 different days, were >220 mg/dl; IFG, if two or more fasting glucose random values, registered on 2 different days, were >110 mg/dl, or IGT, if two or more glucose random values, registered on 2 different days, were >155 mg/dl.…”