Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome.Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics.Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p < 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p < 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p < 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p < 0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p < 0.01).Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis.

Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

“…Its levels can be lowered with the increase of pro-inflammatory cytokines. In addition to contributing to inflammation, such adipokine induces thermogenesis and fatty acid oxidation in skeletal muscle and liver [ 64 , 66 ]. Moreover, adiponectin may contribute to keeping HSCs in their quiescent state [ 65 ].…”

Association between lower plasma adiponectin levels and higher liver stiffness in type 2 diabetic individuals with nonalcoholic fatty liver disease: an observational cross-sectional study

“…Although the results of our study do not have clear implications for clinical practice, they may be important for guiding future mechanistic and intervention studies. In fact, the evidence from this and other studies [11][12][13][14][15][16]18] suggests a possible role of decreased adiponectin levels in the pathophysiology of NAFLD, thus underlining the need for future large-scale studies assessing the predictive as well as the therapeutic role of this adipokine in the spectrum of NAFLD. Additionally, these results may encourage the designing of diagnostic accuracy studies to examine whether plasma adiponectin levels may contribute (alone or in combination with other biomarkers) to the achievement of a non-invasive diagnosis of liver fibrosis.…”

“…In recent years, many observational studies [11][12][13][14][15][16] and some meta-analyses [17] have reported that lower plasma adiponectin levels are significantly associated with the presence and severity of NAFLD, especially in patients without T2DM, thereby suggesting that hypoadiponectinemia might represent a risk factor for NAFLD. However, little information is available to date on the association between lower plasma adiponectin levels and the presence of NAFLD or NASH in patients with T2DM [18].…”

The Endocrine–Metabolic Axis Regulation in Offspring Exposed to Maternal Obesity—Cause or Consequence in Metabolic Disease Programming?

“…Impaired hepatic insulin signaling [91], triglycerides, and increased expression of gluconeogenic enzymes have been reported for MO non-human primate offspring [31]. In addition to adiponectin, serum leptin concentrations are increased in NAFLD subjects [92], suggesting a potential AT dysfunction prior to hepatic fat accumulation, which results in new metabolic homeostasis stimulated by adipokines' levels. HepG2 leptin treatment led to decreased expression of low-density lipoprotein (LDL) receptors and decreased LDL uptake, with augmented proprotein convertase subtilisin/kexin type 9 (PCSK9), which proved essential for the observed response [93].…”