Hashimoto's thyroiditis (HT) is an autoimmune disease, characterized by abnormal elevation in thyroid peroxidase antibody (TPO-Ab) and/or thyroglobulin antibody (TG-Ab). The antibody titers are positively correlated with multiple symptoms despite adequate hormone substitution. However, no specific treatment exists to reduce the levels of antibodies. We carried out a randomized controlled trial to determine the effect of calorie-restricted (CR) diet on Hashimoto disease. Results showed that serum TPO-Ab (-191.46 KU/L, 95% CI: -278.35 to -104.58) and TG-Ab (-49.30 KU/L, 95% CI: -99.12 to 0.53) in the CR group were sharply reduced, accompanied by an improvement in thyroid gland shown by magnetic resonance imaging. The CR group exhibited significant alleviation of non-hypothyroid symptoms, with this improvement positively correlating with the reduction of thyroid antibodies. Moreover, CR also improved immune dysfunction, as well as decreased levels of pro-inflammatory biomarkers and serum lipids. These findings provide evidence that calorie restriction may serve as a potential adjuvant treatment strategy for patients with HT.

Emerging evidence shows that the proportion of dietary macronutrients determines the pathological progression of multiple metabolic diseases, however, whether and how this affect alcohol-associated liver diseases (ALD) are largely unclear. The present study was conducted to explore the role of dietary protein proportions on ALD and to unveil its potential mechanisms. C57BL/6N mice were administrated with isocaloric Lieber-DeCarli alcohol liquid diets with different proportions of protein, including normal protein (NP, 15% energy), high protein (HP, 30% energy), and low protein (LP, 10% energy), respectively. Our results showed that HP diet significantly ameliorated alcohol-induced hepatic steatosis, liver injury, oxidative stress, and inflammation, which were aggravated in LP diet-fed mice. Alcohol consumption-stimulated lipid metabolism-associated genes dysregulation was improved by HP diet. Liver transcriptome sequencing analysis and further validation identified that alcohol dramatically down-regulated 3-hydroxybutyrate dehydrogenase 2 (Bdh2) along with the reduction of β-hydroxybutyric acid, which were rescued by HP diet intervention. Bdh2 was also decreased in the liver of patients with ALD and alcohol-exposed hepatocytes. Spearman correlation analysis revealed that Bdh2 was negatively associated with the indices of hepatic steatosis, liver injury, and oxidative stress. Genetically knocking-down Bdh2 significantly enhanced alcohol-induced hepatotoxicity, lipid accumulation, and pro-inflammatory factors expression in cultured hepatocytes. In summary, HP diet intervention alleviates chronic alcohol consumption induced liver dysfunction in mice. BDH2 is a potential novel target for ALD prevention via restoring the ketogenic pathway that contributes to HP diet-improved ALD. HP dietary pattern might be a promising choice for ALD management.