Controlled lipid β-oxidation and carnitine biosynthesis by a vitamin D metabolite

Mendoza, Aileen; Takemoto, Yasushi; Cruzado, Kevin; Masoud, Shadi Sedghi; Nagata, Akihisa; Tantipanjaporn, Ajcharapan; Okuda, Satoshi; Kawagoe, Fumihiro; Sakamoto, Ryota; Odagi, Minami; Mototani, Sayuri; Togashi, Moeka; Kawatani, Masahito; Aono, Harumi; Osada, Hiroyuki; Nakagawa, Hayato; Higashi, Tatsuya; Kittaka, Atsushi; Nagasawa, Kazuo; Uesugi, Motonari

doi:10.1016/j.chembiol.2021.08.008

Cited by 12 publications

(8 citation statements)

References 57 publications

(53 reference statements)

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“…Population-based studies have shown that vitamin level was closely related to lipid metabolism [ 72 ]. Vitamin D may affect lipid profiles by reducing intestinal absorption of lipids, endogenic lipid synthesis, stimulating lipolysis, and improving lipid metabolism [ 73 , 74 ]. Vitamin E exerts its antioxidant effects by preventing lipid peroxidation [ 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Identifying potential therapeutic targets of mulberry leaf extract for the treatment of type 2 diabetes: a TMT-based quantitative proteomic analysis

Shi,

Wang,

et al. 2023

BMC Complement Med Ther

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Background Mulberry (Morus alba L.) leaf, as a medicinal and food homologous traditional Chinese medicine, has a clear therapeutic effect on type 2 diabetes mellitus (T2DM), yet its underlying mechanisms have not been totally clarified. The study aimed to explore the mechanism of mulberry leaf in the treatment of T2DM through tandem mass tag (TMT)—based quantitative proteomics analysis of skeletal muscle. Methods The anti-diabetic activity of mulberry leaf extract (MLE) was evaluated by using streptozotocin-induced diabetic rats at a dose of 4.0 g crude drug /kg p.o. daily for 8 weeks. Fasting blood glucose, body weight, food and water intake were monitored at specific intervals, and oral glucose tolerance test and insulin tolerance test were conducted at the 7th and 8th week respectively. At the end of the experiment, levels of glycated hemoglobin A1c, insulin, free fat acid, leptin, adiponectin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were assessed and the pathological changes of rat skeletal muscle were observed by HE staining. TMT-based quantitative proteomic analysis of skeletal muscle and bioinformatics analysis were performed and differentially expressed proteins (DEPs) were validated by western blot. The interactions between the components of MLE and DEPs were further assessed using molecular docking. Results After 8 weeks of MLE intervention, the clinical indications of T2DM such as body weight, food and water intake of rats were improved to a certain extent, while insulin sensitivity was increased and glycemic control was improved. Serum lipid profiles were significantly reduced, and the skeletal muscle fiber gap and atrophy were alleviated. Proteomic analysis of skeletal muscle showed that MLE treatment reversed 19 DEPs in T2DM rats, regulated cholesterol metabolism, fat digestion and absorption, vitamin digestion and absorption and ferroptosis signaling pathways. Key differential proteins Apolipoprotein A-1 (ApoA1) and ApoA4 were successfully validated by western blot and exhibited strong binding activity to the MLE’s ingredients. Conclusions This study first provided skeletal muscle proteomic changes in T2DM rats before and after MLE treatment, which may help us understand the molecular mechanisms, and provide a foundation for developing potential therapeutic targets of anti-T2DM of MLE. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Identifying potential therapeutic targets of mulberry leaf extract for the treatment of type 2 diabetes: a TMT-based quantitative proteomic analysis

Shi,

Wang,

et al. 2023

BMC Complement Med Ther

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“…In the present study, the effect on acetone could indicate an effect of vitamin D on the beta-oxidation of fatty acids and thereby the formation and accumulation of ketone bodies. Recently, it was discovered that lactone-vitamin D 3 , a vitamin D 3 metabolite, impairs fatty acid beta-oxidation in vitro [ 33 ]. In the VITdAL-ICU trial, the authors found decreased concentrations of metabolites associated with beta-oxidation after administration of vitamin D 3 [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

The Diurnal Blood Metabolome and Effects of Vitamin D Supplementation: A Randomised Crossover Trial in Postmenopausal Women

Espersen

Correia²,

Rejnmark³

et al. 2022

IJMS

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A way to maintain an adequate vitamin D status is through supplementation. Demonstration of blood-metabolome rhythmicity of vitamin D3 post-dosing effects is lacking in the pharmaco-metabonomics area. Thus, the overall aim of this study was to investigate the diurnal changes in the blood metabolome and how these are affected by vitamin D3 supplementation. The study was conducted as a crossover study, and the treatment included 200 µg (8000 IU) of vitamin D3 as compared with placebo with a washout period of at least 10 days. The participants were postmenopausal women aged 60–80 years (N = 29) with vitamin D insufficiency (serum 25-hydroxyvitamin D < 50 nmol/L) but otherwise healthy. During the intervention day, blood samples were taken at 0 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, and 24 h, and plasma was analysed by proton nuclear magnetic resonance (NMR) spectroscopy as a metabolomics approach. In general, diurnal effects were identified for the majority of the 20 quantified metabolites, and hierarchical cluster analysis revealed a change in the overall plasma metabolome around 12 AM (6 h after intervention), suggesting that the diurnal rhythm is reflected in two diurnal plasma metabolomes; a morning metabolome (8–12 AM) and an afternoon/evening metabolome (2–8 PM). Overall, the effect of vitamin D supplementation on the blood metabolome was minor, with no effect on the diurnal rhythm. However, a significant effect of the vitamin D supplementation on plasma acetone levels was identified. Collectively, our findings reveal an influence of diurnal rhythm on the plasma metabolome, while vitamin D supplementation appears to have minor influence on fluctuations in the plasma metabolome.

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“…(1,25(OH)2D3), which is able to be recognized by vitamin D receptor (VDR) [24,25]. The most reported function of vitamin D is to maintain calcium homeostasis and bone integrity.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D prevents gestational diabetes mellitus via modulating glycometabolism

Gu,

Chen,

Liu

2023

Preprint

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Gestational diabetes mellitus (GDM) is a common disease during pregnancy that has adverse effects on both the mother and fetus. There is currently no systematically research on the effect of vitamin supplementation on GDM pregnant mother and their offspring. This work supplemented the GDM pregnant mouse model with vitamin D and found that vitamin D can effectively alleviate the hyperglycemia in GDM pregnant mice, increase blood insulin and adiponectin concentrations, and improve GTT and ITT in pregnant mice. In addition, vitamin D can reduce the incidence of death and high birth weight of offspring caused by GDM. The offspring of GDM pregnant mice had higher blood glucose levels in the first 5 weeks after birth compared to the normal group, and then returned to normal levels. Vitamin D can alleviate abnormal glucose metabolism in newborn mice. The therapeutic effect exhibited by vitamin D may be due to their anti-inflammatory effects, as vitamin D supplementation significantly reduces the levels of TFN-α, MCP-1, IL-1β and IL-8 in the blood. Vitamin D also regulates liver lipid metabolism, resulting in a decrease in liver lipid accumulation and a decrease in blood triglycerides (TG), cholesterol (CHO) and high-density lipoprotein (HDL). The results of this study demonstrate that vitamin D supplementation can serve as an effective treatment strategy for alleviating GDM symptoms.

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Controlled lipid β-oxidation and carnitine biosynthesis by a vitamin D metabolite

Cited by 12 publications

References 57 publications

Identifying potential therapeutic targets of mulberry leaf extract for the treatment of type 2 diabetes: a TMT-based quantitative proteomic analysis

Identifying potential therapeutic targets of mulberry leaf extract for the treatment of type 2 diabetes: a TMT-based quantitative proteomic analysis

The Diurnal Blood Metabolome and Effects of Vitamin D Supplementation: A Randomised Crossover Trial in Postmenopausal Women

Vitamin D prevents gestational diabetes mellitus via modulating glycometabolism

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