The role of thyroid status in modulating the level of neuroregulin-4 (NRG4) in non-alcoholic fatty liver disease

Introduction. Thyroid diseases are the most common endocrine pathology. Neuregulin-4 (NRG4) is an adipokine secreted by brown adipose tissue, with reduced levels in non-alcoholic fatty liver disease (NAFLD). The influence of thyroid status on NRG4 has been insufficiently studied.

Aim. To investigate NRG4 levels in men with NAFLD and different thyroid status.

Materials and methods. This cross-sectional study included men aged 32–49 years with NAFLD (n = 70), divided by thyroid status: hypothyroidism (n = 25), subclinical hyperthyroidism (n = 20), and normothyroidism (n = 25). The control group consisted of 26 men without thyroid or liver pathology. All participants underwent point shear wave elastography (pSWE) of the liver.

Results. The NRG4 level in the overall NAFLD group was significantly lower than in controls: 2.1 (1.6; 3.8) ng/ml vs. 2.95 (2.92; 2.96) ng/ml (p = 0.041). Stratification revealed multidirectional dynamics: decreased NRG4 in normo- (1.6 ng/ml) and hypothyroidism (2.2 ng/ml), and increased levels in subclinical hyperthyroidism (4.0 ng/ml). In hypothyroidism, NRG4 correlated with liver stiffness (r = 0.406); in hyperthyroidism, it correlated with body mass index (r = -0.391).

Conclusions. In patients with NAFLD and hypothyroidism, NRG4 levels are lower than in those with hyperthyroidism. Hypothyroidism may exacerbate NAFLD progression by suppressing the protective adipokine NRG4. The paradoxical increase in NRG4 in subclinical hyperthyroidism, despite high liver stiffness, is likely a compensatory response to metabolic stress.

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