Research Article Details
| Article ID: | A08955 |
| PMID: | 31926452 |
| Source: | J Nutr Biochem |
| Title: | The nonalcoholic fatty liver disease-like phenotype and lowered serum VLDL are associated with decreased expression and DNA hypermethylation of hepatic ApoB in male offspring of ApoE deficient mothers fed a with Western diet. |
| Abstract: | Increasing evidence indicates that the intra-uterine environment has consequences for later life. However, the mechanisms of this fetal programming remain unclear. We aimed to investigate the impact of diet-induced maternal hypercholesterolemia on the predisposition of offspring to nonalcoholic fatty liver diseases (NAFLD) and metabolic diseases and its underlying mechanisms. Female apolipoprotein (Apo) E-deficient mice were fed a control diet (CD) or high fat/high cholesterol Western-type diet (WD) before and throughout pregnancy and lactation, and their offspring were weaned onto a CD postnatally. Strikingly, male offspring of WD-fed dams developed glucose intolerance and decreased peripheral insulin sensitivity and exhibited hepatic steatosis. Hepatic steatosis could be attributed, at least in part, to increased hepatic lipogenesis in E18.5 embryos and decreased serum VLDL levels in adulthood. In addition, males born to WD-fed dams had lower serum ApoB levels and hepatic ApoB gene expression compared with males born to CD-fed dams. DNA methylation analysis revealed increased methylation of CpG dinucleotides on the promoter region of the ApoB genes in the livers of male offspring of WD-fed dams. Our findings suggest that maternal WD intake can exacerbate the development of NAFLD in male offspring potentially by affecting ApoB gene expression through epigenetic alterations. |
| DOI: | 10.1016/j.jnutbio.2019.108319 |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |