Arola, L. | bioRxiv Science

bioRxiv2021

Combined Metabolic Activators decrease liver steatosis by activating mitochondrial metabolism in a Golden Syrian hamster study

The prevalence of non-alcohol fatty liver disease (NAFLD), defined as the livers excessive fat accumulation, continues to increase dramatically. We have recently revealed the molecular mechanism underlying NAFLD using in-depth multi-omics profiling and identified that combined metabolic activators (CMA) could be administered to decrease the amount of hepatic steatosis (HS) in mouse model and NAFLD patients based on systems analysis. Here, we investigated the effects of a CMA including L-carnitine, N-acetyl-l-cysteine, nicotinamide riboside and betaine on a Golden Syrian hamster NAFLD model fed with HFD, and found that HS was decreased with the administration of CMA. To explore the mechanisms involved in the clearance HS, we generated liver transcriptomics data before and after CMA administration, and integrated these data using liver-specific genome-scale metabolic model of liver tissue. We systemically determined the molecular changes after the supplementation of CMAs and found that it activates mitochondria in the liver tissue by modulating the global fatty acid, amino acids, antioxidant and folate metabolism.

systems biology↗

bioRxiv2019

Obesity-induced gut microbiota dysbiosis can be ameliorated by fecal microbiota transplantation: a multiomics approach.

Obesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Recently, the gut microbiota has emerged as a new potential therapeutic target for the treatment of obesity. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent a strategy for obesity treatment. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function.\n\nTo do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as an obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption.

systems biology↗