Research Article Details
| Article ID: | A16729 |
| PMID: | 28219837 |
| Source: | J Nutr Biochem |
| Title: | Chronic maternal calcium and 25-hydroxyvitamin D deficiency in Wistar rats programs abnormal hepatic gene expression leading to hepatic steatosis in female offspring. |
| Abstract: | Importance of calcium and vitamin D deficiency is well established in adult dyslipidemia. We hypothesized that maternal calcium and vitamin D deficiency could alter offspring's lipid metabolism. Our objective was to investigate the effect of maternal dietary calcium and vitamin D deficiency on lipid metabolism and liver function of the F1 generation offspring. intergenerational calcium-deficient (CaD) and vitamin D-deficient (VDD) models were developed by mating normal male rats with deficient females and continuing maternal-deficient diets through pregnancy and lactation. Offspring were fed on control diet post-weaning and studied till 30 weeks. Lipid profile, serum glutamate pyruvate transaminase (SGPT), calcium and vitamin D levels were analyzed. Liver fat deposition, omega-3 fatty acids level and mRNA expression levels of peroxisome proliferator-activated receptor-alpha (PPAR-α), sterol regulatory element-binding protein 1c (SREBP-1c), interleukin 6 (IL-6), superoxide dismutase 1 (SOD-1) and uncoupling protein 2 (UCP2) were determined. Low serum vitamin D levels with an increase in SGPT and TG levels in CaD and VDD female offspring were observed. Severe liver steatosis with down-regulation of PPAR-α and UCP2 and up-regulation of SREBP-1c, IL-6 and SOD-1 was observed in the female offspring born to deficient dams. CaD and VDD male offspring showed mild steatosis and down-regulation of UCP2 and SOD-1. We conclude that maternal calcium and vitamin D deficiency programs abnormal lipid metabolism and hepatic gene expression in the F1 generation female offspring leading to hepatic steatosis, despite feeding them on control diet post-weaning. |
| DOI: | 10.1016/j.jnutbio.2017.01.008 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I02 | 5113 | Nutritional deficiency disease | A nutrition disease that is characterized by deficiency of a nutritional element, such as a vitamin, mineral, carbohydrate, protein, fat, or general energy content. https://medlineplus.gov/malnutrition.html | disease of metabolism/acquired metabolic disease/nutrition disease | Details |
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D258 | Omega 3 PUFA | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Hypolipidemic drug | Under clinical trials | Details |
| D387 | Vitamin D | Supplement | DB11094 | -- | Vitamin source drug | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D527 | EPA/DHA | Supplement | DB11133 | -- | -- | Under clinical trials | Details |
| D055 | Calcium | Chemical drug | DB01373 | CAST; COMP; CP; BMP4; MGP | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D125 | Epanova | Chemical drug | DB11133 | PPARG ligand; PPARA activator | Enhance lipid metabolism | Under clinical trials | Details |