Research Article Details
| Article ID: | A13215 |
| PMID: | 30079055 |
| Source: | Front Microbiol |
| Title: | Genetically Obese Human Gut Microbiota Induces Liver Steatosis in Germ-Free Mice Fed on Normal Diet. |
| Abstract: | Dysbiotic gut microbiota contributes to genetically obese phenotype in human. However, the effect of genetic obesity-associated gut microbiota on host hepatic metabolic deteriorations remains largely unknown. Gut microbiota from a genetically obese human donor before and after a dietary weight loss program was transplanted into germ-free C57BL/6J male mice, grouped as PreM and PostM groups, respectively. The gut microbiome, liver pathology and transcriptome response in the gnotobiotic mice were evaluated. After being fed on normal chow diet for 4 weeks, PreM group developed liver macrovesicular steatosis accompanied with higher concentrations of hepatic triglyceride and cholesterol, while PostM group exhibited normal hepatic physiology. The gut microbiota in PreM and PostM groups was significantly different from each other and was more resembling with their respective donor. RNA-sequencing revealed that, in comparison with PostM group, PreM group showed a foregoing pro-steatotic transcriptional response in liver featuring by the repression of lipid beta-oxidation and the activation of lipid absorption and cholesterol uptake before the pathology of liver steatosis. Moreover, peroxisome proliferator-activated receptor alpha (PPARα), which was repressed in PreM group, may act as crucial regulator of the hepatic transcriptional profile of lipid metabolism between two groups. Our results show that gut microbiota from a genetically obese human promotes the onset of liver steatosis by impacting hepatic transcriptional profile of lipid metabolism in mice. This adds new evidence that gut microbiota may play a causative role in the development of non-alcoholic fatty liver disease. |
| DOI: | 10.3389/fmicb.2018.01602 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S06 | Regulating intestinal flora | intestine gut microbiota; gut microbiota | farnesoid X receptor (FXR); fibroblast growth factor-19 (FGF19) | Probiotics; Prebiotics; Rifaximin; Yaq-001; Cilofexor; EDP-305; EYP001a; INT-767 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T03 | Peroxisome proliferator-activated receptor alpha | PPARA | agonist | Nuclear hormone receptor | Q07869 | PPARA_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |