Vitamin D decreases adipocyte lipid storage and increases NAD-SIRT1 pathway in 3T3-L1 adipocytes

Chang, Eugene; Kim, Yangha

doi:10.1016/j.nut.2015.12.032

Cited by 86 publications

(76 citation statements)

References 50 publications

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“…For example, Chang et al [31] recently demonstrated that 1,25(OH) 2 D significantly reduced neutral lipid accumulation in 3T3-L1 adipocytes. Given the role of PC in regulation of lipid accumulation in the same cell line [17], it is possible that 1,25(OH) 2 D exerts its effect on adipocyte lipid accumulation through downregulation of PC, similar to what we have characterized in the present study in malignant breast epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

1α,25-dihydroxyvitamin D inhibits de novo fatty acid synthesis and lipid accumulation in metastatic breast cancer cells through down-regulation of pyruvate carboxylase

Wilmanski

Buhman

Donkin

et al. 2017

The Journal of Nutritional Biochemistry

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Both increased de novo fatty acid synthesis and higher neutral lipid accumulation are a common phenotype observed in aggressive breast cancer cells, making lipid metabolism a promising target for breast cancer prevention. In the present studies we demonstrate a novel effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)2D) on lipid metabolism in malignant breast epithelial cells. Treatment of MCF10CA1a breast epithelial cells with 1,25(OH)2D (10 nM) for five and seven days decreased the level of triacylglycerol, the most abundant form of neutral lipids, by 20%(±3.9) and 50%(±5.9), respectively. In addition, 1,25(OH)2D treatment for five days decreased palmitate synthesis from glucose, the major fatty acid synthesized de novo (48%±5.5 relative to vehicle). We have further identified the anaplerotic enzyme pyruvate carboxylase (PC) as a target of 1,25(OH)2D mediated regulation and hypothesized that 1,25(OH)2D regulates breast cancer cell lipid metabolism through inhibition of PC. PC mRNA expression was downregulated with 1,25(OH)2D treatment at two (73%±6 relative to vehicle) and five (56%±8 relative to vehicle) days. Decrease in mRNA abundance corresponded with a decrease in PC protein expression at five days of treatment (54%±12 relative to vehicle). Constitutive overexpression of PC in MCF10CA1a cells using a pCMV6-PC plasmid inhibited the effect of 1,25(OH)2D on both TAG accumulation and de novo palmitate synthesis from glucose. Together, these studies demonstrate a novel mechanism through which 1,25(OH)2D regulates lipid metabolism in malignant breast epithelial cells.

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Section: Discussionmentioning

confidence: 99%

1α,25-dihydroxyvitamin D inhibits de novo fatty acid synthesis and lipid accumulation in metastatic breast cancer cells through down-regulation of pyruvate carboxylase

Wilmanski

Buhman

Donkin

et al. 2017

The Journal of Nutritional Biochemistry

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“…SIRT1 protects diet-induced obesity and inflammation and obesity-associated metabolic dysfunction [36,37,38,39]. In addition, vitamin D decreases adipocyte fat accumulation and increases SIRT1 activation in adipocytes [40]. Thus, AMPK and SIRT1 activation have been proposed as key regulators to prevent obesity and obesity-related metabolic dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Insufficiency Exacerbates Adipose Tissue Macrophage Infiltration and Decreases AMPK/SIRT1 Activity in Obese Rats

Chang

Kim

2017

Nutrients

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Obesity is recognized as a state of chronic low-grade systemic inflammation due to adipose tissue macrophage infiltration and production of proinflammatory adipokines. Decreased vitamin D status is associated with obesity. The specific aim of the present study is to investigate the effects of vitamin D on obesity-induced adipose tissue inflammation. Male Sprague-Dawley rats were randomized and fed a normal diet (NOR, 1000 IU vitamin D/kg diet), a 45% high-fat diet (HF, 1000 IU vitamin D/kg diet), or a 45% high-fat diet containing 25 IU vitamin D/kg diet (HF+LVD) for 12 weeks. The vitamin D-insufficient diet (HF+LVD) led to vitamin D inadequacy as determined by serum 25(OH)D level, 68.56 ± 7.97 nmol/L. The HF+LVD group exacerbated HF-increased adipocyte size, adipogenic gene expression of PPARγ, adipose tissue macrophage recruitment, and proinflammatory cytokine IL-6 and TNFα levels in epididymal white adipose tissue. In addition, vitamin D insufficiency significantly decreased mRNA levels of β-oxidation-related genes such as CPT1α, PGC1α, PPARα, VLCAD, LCAD, MCAD, and UCP1. Moreover, significant decrements of SIRT1 and AMPK activity were noted in obese rats fed with a vitamin D-insufficient diet. The observed deleterious effects of vitamin D insufficiency on adipose tissue expansion, immune cell infiltration and inflammatory status suggest vitamin D plays a beneficial role in adipocyte metabolic metabolism and obesity progression. SIRT1 and AMPK activity may play a role in the mechanism of vitamin D action.

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“…Recent findings highlight the role of vitamin D and its active form 1,25(OH)2D in influencing the gene expression of key molecules involved in adipogenesis [12], fat oxidation and lipolysis by the activation of the nicotinamide adenine dinucleotide (NAD)-dependent sirtuin1 pathway [13]. Vitamin D3 has a range of physiological functions in the body, the most important being the maintenance of the calcium and phosphorus balance [14] in osteoblasts, where it usually inhibits cellular proliferation and induces differentiation [15].…”

Section: Introductionmentioning

confidence: 99%

Melatonin and Vitamin D Interfere with the Adipogenic Fate of Adipose-Derived Stem Cells

Basoli

Santaniello

Cruciani

et al. 2017

IJMS

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Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer. Here, we aimed at evaluating the effects elicited by melatonin, even in the presence of vitamin D, on ADSC adipogenesis assessed in a specific medium. The transcription of specific adipogenesis orchestrating genes, such as aP2, peroxisome proliferator-activated receptor γ (PPAR-γ), and that of adipocyte-specific genes, including lipoprotein lipase (LPL) and acyl-CoA thioesterase 2 (ACOT2), was significantly inhibited in cells that had been treated in the presence of melatonin and vitamin D, alone or in combination. Protein content and lipid accumulation confirmed a reduction in adipogenesis in ADSCs that had been grown in adipogenic conditions, but in the presence of melatonin and/or vitamin D. Our findings indicate the role of melatonin and vitamin D in deciding stem cell fate, and disclose novel therapeutic approaches against fat depots.

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Vitamin D decreases adipocyte lipid storage and increases NAD-SIRT1 pathway in 3T3-L1 adipocytes

Cited by 86 publications

References 50 publications

1α,25-dihydroxyvitamin D inhibits de novo fatty acid synthesis and lipid accumulation in metastatic breast cancer cells through down-regulation of pyruvate carboxylase

1α,25-dihydroxyvitamin D inhibits de novo fatty acid synthesis and lipid accumulation in metastatic breast cancer cells through down-regulation of pyruvate carboxylase

Vitamin D Insufficiency Exacerbates Adipose Tissue Macrophage Infiltration and Decreases AMPK/SIRT1 Activity in Obese Rats

Melatonin and Vitamin D Interfere with the Adipogenic Fate of Adipose-Derived Stem Cells

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