Neuregulin-4 (Nrg-4) as a Metabolic Regulator: A Comprehensive Review of Its Association with Dyslipidemia and Liver Function Abnormalities in Newly Diagnosed Type 2 Diabetes Mellitus

Abstract

Neuregulin-4 (Nrg-4), a brown adipose tissue–derived adipokine, has emerged as a critical endocrine regulator linking adipose tissue function with metabolic homeostasis. Growing evidence suggests that reduced Nrg-4 levels are associated with insulin resistance, dyslipidemia, hepatic steatosis, and the early pathophysiology of type 2 diabetes mellitus (T2DM). This review explores in depth the correlation between circulating Nrg-4 levels, lipid parameters, and liver function markers among newly diagnosed T2DM patients, highlighting its potential as a diagnostic or prognostic biomarker. “Research consistently indicates that individuals with diabetes exhibit markedly reduced Nrg-4 levels, which show inverse associations with triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) whereas Nrg-4 demonstrates a positive correlation with high-density lipoprotein cholesterol (HDL-C)”. Mechanistic studies support a protective role of Nrg-4 against hepatic lipogenesis, oxidative stress, and systemic inflammation. The findings collectively indicate that Nrg-4 is detrimental in metabolic regulation and could act as promising biomarker for early metabolic derangements in diabetes. Nevertheless, heterogeneity in study design, limited sample sizes, and assay variability highlight the need for standardized large-scale cohort studies.