Serum IL-27 levels increase in subjects with hypothyroidism and are negatively correlated with the occurrence of nonalcoholic fatty liver disease

Abstract

BackgroundThe level of serum interleukin-27 (IL-27) was significantly decreased in the obesity group. After injection of IL-27, obese mice showed significant weight loss,reduced fat accumulation, improved insulin resistance and hepatic steatosis.IL-27 plays a key role in the regulation of metabolic processes, but there are scarce data on circulating IL-27 levels in hypothyroidism. The purpose of this study was to assess the serum levels of IL-27 in patients with hypothyroidism and its relationship with NAFLD.Methods185 participants were included in this cross-sectional survey. According to thyroid function, the subjects were classified into three groups: euthyroidism (n = 55), subclinical hypothyroidism (n = 53), and hypothyroidism (n = 77). Serum IL-27 concentrations were measured by ELISA.ResultsSerum IL27 levels were significantly higher in subclinical hypothyroidism and hypothyroidism groups than in the euthyroidism group. Serum IL27 levels had a negative correlation with HOMA-IR,FBG,TG, subcutaneous fat,and visceral fat, and had a positive correlation with HDL-C (P< 0.05). Furthermore, logistic regression analysis indicated that IL-27 levels, HOMA-IR, and visceral fat showed significant associations with NAFLD after complete adjustment (P< 0.05). ROC curves showed that theoptimal cut-off value of serum IL-27 for discriminating NAFLD was 95.87pg/mL. The area under the ROC curve was 77.3% (95% CI = 0.694-0.851, p < 0.001).ConclusionsSerum IL-27 levels demonstrated a compensatory increase in patients with subclinical hypothyroidism or hypothyroidism and showed an independent association with NAFLD. Circulating IL-27 levels could predict the occurrence of NAFLD in hypothyroidism. These results suggested that altering the circulating levels of IL-27 may be a potential therapeutic target for NAFLD.

Thyroid function, adipokines and mitokines in metabolic dysfunction‐associated steatohepatitis: A multi‐centre biopsy‐based observational study

“…It is known that decreased thyroid function leads to the up‐regulation of proinflammatory adipokines (such as leptin) and the decrease of the insulin sensitizer adiponectin, 33 which may contribute to liver inflammation and fibrosis 60 . Furthermore, pathways related to inflammation and oxidative stress are also crucial for the development of NAFLD and NASH 61 . We also evaluated the novel mitokine total GDF‐15 as a promising molecule associated with MASLD development and progression 33 to generate hypotheses about potential causal pathways that might mediate the association between thyroid dysfunction and MASLD severity.…”

“…60 Furthermore, pathways related to inflammation and oxidative stress are also crucial for the development of NAFLD and NASH. 61 We also evaluated the novel mitokine total GDF-15 as a promising molecule associated with MASLD development and progression 33 to generate hypotheses about potential causal pathways that might mediate the association between thyroid dysfunction and MASLD severity.…”

Casual associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines

“…( 53 ) identified a significant correlation between TSH concentrations and various populations of effector and regulatory T cells through analysis of the immunological phenotype from the Human Functional Genomics Project. Serum IL-27 levels are elevated in subjects with hypothyroidism and inversely correlate with the incidence of nonalcoholic fatty liver disease ( 54 ). Hypothyroidism is linked to immunosuppression, which is attributed to increased frequency and activity of Gal-1-expressing Tregs, with significant implications for immunopathology, metabolic disorders, and cancer ( 55 ).…”