Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background, and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants and diabetes, 56 heterogenous MAFLD patients are characterized by generating multiomics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. The dysbiosis in the oral and gut microbiome is explored and the host-microbiome interactions based on global metabolic and inflammatory processes are revealed. These multiomics data are integrated using the biological network and HS's key features are identified using multiomics data. HS is finally predicted using these key features and findings are validated in a follow-up cohort, where 22 subjects with varying degree of HS are characterized.

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Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.

Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMA) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomics data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we observed that CMA can be used develop a pharmacological treatment strategy in NAFLD patients.

Objective: Metabolic syndrome (MetS) is one of the preventable risk factors for cardiovascular disease (CVD). The aim of this study was to investigate the effect of MetS on CVD and cumulative organ damage in a multi-center, large cohort of patients with Takayasu arteritis (TAK).Methods: This is a cross-sectional study involving 192 consecutive TAK patients from seven tertiary rheumatology centers in Turkey. Clinical data of TAK patients fulfilling the 1990 American College of Rheumatology classification criteria were collected from medical records. They were evaluated for risk factors of CVD, disease activity, damage, and MetS at their last visits.Results: A total of 192 consecutive TAK patients were included in this study. One hundred and fifty-eight (82%) were female, the mean age was 43.3 ± 13 years, and mean disease duration was 13.5 ± 9.3 years. MetS was detected in 50 (26%) of the patients and CVD was detected in 28 (14.6%). The presence of MetS was detected as an independent risk factor for CVD (P < 0.001). In addition, the mean vasculitis damage index of the group with MetS was significantly higher than in the other patients (4.5 ± 3.3 vs 3.2 ± 2.2, respectively, P = 0.004). Conclusion:The presence of MetS in TAK is associated with increased CVD and disease damage. Awareness and management of MetS can improve disease prognosis in patients with TAK.