A case–control study: Association between serum neuregulin 4 level and non-alcoholic fatty liver disease

Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression

“…Interestingly, mRNA expression of Nrg4 in epididymal white adipose tissue (eWAT) and brown adipose tissue (BAT) was significantly decreased in NASH mice ( Figure 1G). These results are consistent with recent work that demonstrates an inverse relationship between plasma Nrg4 levels and NASH scores in human patients (27). As Nrg4 is a fat-derived endocrine factor that acts on the liver, these findings raise the possibility that reduced Nrg4 signaling may contribute to the disruption of tissue homeostasis during steatosis-to-NASH progression.…”

“…Gene ontology analysis indicated that the upregulated genes are highly enriched for extracellular matrix, wound healing, and collametabolic disorders. Interestingly, plasma Nrg4 levels inversely correlated with metabolic syndrome and NAFLD in 2 recent studies (26,27). Recent genome-wide association studies indicate that polymorphisms in the ERBB4 locus are associated with obesity, diabetes, and diabetic nephropathy (28)(29)(30), illustrating a potential contribution of the Nrg4/ErbB4 pathway to the pathogenesis of metabolic disorders.…”

Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults

“…Of note, our data indicated that obese subjects with high levels of circulating Nrg4 had favorable metabolic profiles, including lower levels of BMI, systolic BP, and total cholesterol compared to those with low values. In contrast, Dai and colleague reported that circulating Nrg4 was decreased in NAFLD subjects but not significantly associated with BMI and other metabolic risk factors in a case-control study of 87 NAFLD subjects versus 87 non-NAFLD subjects22.…”

Elevated circulating Neuregulin4 level in patients with diabetes

“…Actually, recent work indeed indicated there was an association between serum Nrg4 levels and the risk of non‐alcoholic fatty liver disease . Whereas, it is still unknown about the circulating Nrg4 levels in population with type 2 diabetes, the condition being imposing a much more tremendous burden both on individuals affected and the whole health care system…”