Research Article Details

Article ID: A45186
PMID: 25774554
Source: Endocrinology
Title: Vitamin d deficiency attenuates high-fat diet-induced hyperinsulinemia and hepatic lipid accumulation in male mice.
Abstract: It is increasingly recognized that vitamin D deficiency is associated with increased risks of metabolic disorders among overweight children. A recent study showed that vitamin D deficiency exacerbated inflammation in nonalcoholic fatty liver disease through activating toll-like receptor 4 in a high-fat diet (HFD) rat model. The present study aimed to further investigate the effects of vitamin D deficiency on HFD-induced insulin resistance and hepatic lipid accumulation. Male ICR mice (35 d old) were randomly assigned into 4 groups as follows. In control diet and vitamin D deficiency diet (VDD) groups, mice were fed with purified diets. In HFD and VDD+HFD groups, mice were fed with HFD. In VDD and VDD+HFD groups, vitamin D in feed was depleted. Feeding mice with vitamin D deficiency diet did not induce obesity, insulin resistance, and hepatic lipid accumulation. By contrary, vitamin D deficiency markedly alleviated HFD-induced overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D deficiency significantly attenuated HFD-induced up-regulation of hepatic peroxisome proliferator-activated receptor γ, which promoted hepatic lipid uptake and lipid droplet formation, and its target gene cluster of differentiation 36. In addition, vitamin D deficiency up-regulated carnitine palmitoyltrans 2, the key enzyme for fatty acid β-oxidation, and uncoupling protein 3, which separated oxidative phosphorylation from ATP production, in adipose tissue. These data suggest that vitamin D deficiency is not a direct risk factor for obesity, insulin resistance, and hepatic lipid accumulation. Vitamin D deficiency alleviates HFD-induced overweight, hyperinsulinemia, and hepatic lipid accumulation through promoting fatty acid β-oxidation and elevating energy expenditure in adipose tissue.
DOI: 10.1210/en.2014-2037

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

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T09 Toll-like receptor 4 TLR4 antagonist Membrane receptor O00206 TLR4_HUMAN Details
T10 Caspase-1 CASP1 inhibitor Enzyme P29466 CASP1_HUMAN Details
T18 Acetyl-CoA carboxylase 1 ACACA inhibitor Enzyme Q13085 ACACA_HUMAN Details
T21 Diacylglycerol O-acyltransferase 2 DGAT2 inhibitor Enzyme Q96PD7 DGAT2_HUMAN Details

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
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

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D579 Emfilermin Miscellany -- adipocytes Enhance lipid metabolism Under investigation Details
D387 Vitamin D Supplement DB11094 -- Vitamin source drug Under clinical trials Details
D201 L-Carnitine Supplement DB00583 SLC22A4; SLC22A5; CRAT; MPO -- Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details
D062 Carnitine complex Supplement DB00583 SLC22A4; SLC22A5; CRAT; MPO -- Under clinical trials Details