Fibroblast growth factor 21 (FGF21) is an endocrine-member of the FGF family. It is synthesized mainly in the liver, but it is also expressed in adipose tissue, skeletal muscle, and many other organs. It has a key role in glucose and lipid metabolism, as well as in energy balance. FGF21 concentration in plasma is increased in patients with obesity, insulin resistance, and metabolic syndrome. Recent findings suggest that such increment protects tissue from an increased oxidative stress environment. Different types of physical stress, such as strenuous exercising, lactation, diabetic nephropathy, cardiovascular disease, and critical illnesses, also increase FGF21 circulating concentration. FGF21 is now considered a stress-responsive hormone in humans. The discovery of an essential response element in the FGF21 gene, for the activating transcription factor 4 (ATF4), involved in the regulation of oxidative stress, and its relation with genes such as NRF2, TBP-2, UCP3, SOD2, ERK, and p38, places FGF21 as a key regulator of the oxidative stress cell response. Its role in chronic diseases and its involvement in the treatment and follow-up of these diseases has been recently the target of new studies. The diminished oxidative stress through FGF21 pathways observed with anti-diabetic therapy is another clue of the new insights of this hormone.

Background: Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Recently, the term metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed and adapted to body mass index (BMI). This study describes the impact on prevalence of the application of both criteria in overweight and lean patients. Methods: Patients who were evaluated for liver steatosis by transient elastography were included and divided according to BMI (≥25 kg/m² and <25 kg/m²) and classified as NAFLD or MAFLD, according to metabolic abnormalities. Differences in prevalence were evaluated applying both criteria. A multivariate analysis was performed to evaluate independent associations of metabolic abnormalities and liver steatosis in lean patients. Results: 3847 patients were included. In overweight patients (61%), the prevalence NAFLD was 63.6% and 65.3% for MAFLD (p = 0.22). In contrast, the prevalence of MAFLD was lower (7.9% vs. 18.3%, p ≤ 0.001) in lean patients. In this group, higher age, fasting glucose, triglycerides, and waist circumference showed independent association with liver steatosis. Conclusion: The application of NAFLD/MAFLD criteria did not show prevalence differences in overweight patients. With MAFLD criteria, the prevalence is lower in lean patients, but patients with high risk of progression of liver disease for steatosis were identified, according to their metabolic abnormalities.

Background: The association of low–normal thyroid function (LNTF) with non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) is controversial; thus, the aim of this study is to determine this association. Methods: NAFLD was evaluated by controlled attenuation parameter of transient elastography. Patients were classified by MAFLD criteria. LNTF was defined as TSH levels of 2.5 to 4.5 mIU/L and were divided into three different cut-off points (>4.5 to 5.0, >3.1, and >2.5 mIU/L). Associations between LNTF, NAFLD, and MAFLD were evaluated by univariate and multivariate logistic regression analyses. Results: A total of 3697 patients were included; 59% (n = 2179) were male, and median age and body mass index were 48 (43–55) years and 25.9 (23.6–28.5) kg/m², respectively, and 44% (n = 1632) were diagnosed with NAFLD. THS levels of 2.5 and 3.1 showed significant associations with the presence of NAFLD and MAFLD; however, LNTF did not show an independent association with the presence of NAFLD or MAFLD in multivariate analysis. According to different cut-off points, patients with LNTF presented similar risks for NAFLD as the general population. Conclusion: LNTF is not associated with NAFLD or MAFLD. Patients with high LNTF are equally at risk for NAFLD as the general population.