Research Article Details
| Article ID: | A14240 |
| PMID: | 29509436 |
| Source: | Am J Physiol Endocrinol Metab |
| Title: | Developmental origins of nonalcoholic fatty liver disease as a risk factor for exaggerated metabolic and cardiovascular-renal disease. |
| Abstract: | Intrauterine growth restriction (IUGR) is linked to increased risk for chronic disease. Placental ischemia and insufficiency in the mother are implicated in predisposing IUGR offspring to metabolic dysfunction, including hypertension, insulin resistance, abnormalities in glucose homeostasis, and nonalcoholic fatty liver disease (NAFLD). It is unclear whether these metabolic disturbances contribute to the developmental origins of exaggerated cardiovascular-renal disease (CVRD) risk accompanying IUGR. IUGR impacts the pancreas, adipose tissue, and liver, which are hypothesized to program for hepatic insulin resistance and subsequent NAFLD. NAFLD is projected to become the major cause of chronic liver disease and contributor to uncontrolled type 2 diabetes mellitus, which is a leading cause of chronic kidney disease. While NAFLD is increased in experimental models of IUGR, lacking is a full comprehension of the mechanisms responsible for programming of NAFLD and whether this potentiates susceptibility to liver injury. The use of well-established and clinically relevant rodent models, which mimic the clinical characteristics of IUGR, metabolic disturbances, and increased blood pressure in the offspring, will permit investigation into mechanisms linking adverse influences during early life and later chronic health. The purpose of this review is to propose mechanisms, including those proinflammatory in nature, whereby IUGR exacerbates the pathogenesis of NAFLD and how these adverse programmed outcomes contribute to exaggerated CVRD risk. Understanding the etiology of the developmental origins of chronic disease will allow investigators to uncover treatment strategies to intervene in the mother and her offspring to halt the increasing prevalence of metabolic dysfunction and CVRD. |
| DOI: | 10.1152/ajpendo.00394.2017 |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| 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 |