Research Article Details
| Article ID: | A13474 |
| PMID: | 29956209 |
| Source: | Adv Exp Med Biol |
| Title: | The Influence of Gut Microbial Metabolism on the Development and Progression of Non-alcoholic Fatty Liver Disease. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is defined as the presence of excess fat in the liver parenchyma in the absence of excess alcohol consumption and overt inflammation. It has also been described as the hepatic manifestation of metabolic syndrome (Than NN, Newsome PN, Atherosclerosis. 239:192-202, 2015). The incidence of NAFLD has been reported to be 43-60% in diabetics, ~90% in patients with hyperlipidemia and 91% in morbidly obese patients (Than NN, Newsome PN, Atherosclerosis. 239:192-202, 2015, Machado M, Marques-Vidal P, Cortez-Pinto H, J Hepatol, 45:600-606, 2006, Vernon G, Baranova A, Younossi ZM, Aliment Pharmacol Ther, 34:274-285, 2011). The risk factors that have been associated with the development of NAFLD include male gender, increasing age, obesity, insulin resistance, diabetes and hyperlipidemia (Attar BM, Van Thiel DH, Sci World J, 2013:481893, 2013, Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A, Forum Nutr, 5:1544-1460, 2013). All of these risk factors have been linked to alterations of the gut microbiota, ie., gut dysbiosis (He X, Ji G, Jia W, Li H, Int J Mol Sci, 17:300, 2016). However, it must be pointed out that the prevalence of NAFLD in normal weight individuals without metabolic risk factors is ~16% (Than NN, Newsome PN, Atherosclerosis. 239:192-202, 2015). This fact has led some investigators to hypothesize that the gut microbiota can impact lipid metabolism in the liver independently of obesity-related metabolic factors (Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold g, et al., Gut, 65:330 339, 2016) (Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C, et al., Gut, 62:1787-1794, 2013). In this chapter, we will explore the effect of the gut microbiota on hepatic lipid metabolism and how this affects the development of NAFLD. |
| DOI: | 10.1007/978-981-10-8684-7_8 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | 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 |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| 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 |
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease | Details |