Vitamin D3/VDR resists diet-induced obesity by modulating UCP3 expression in muscles

Fan, Yue; Futawaka, Kumi; Koyama, Rie; Fukuda, Yuki; Hayashi, Misa; Imamoto, Miyuki; Miyawaki, Takashi; Kasahara, Masato; Tagami, Tetsuya; Moriyama, Kenji

doi:10.1186/s12929-016-0271-2

Cited by 35 publications

(29 citation statements)

References 49 publications

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“…25(OH)D 3 and 1,25(OH) 2 D 3 repletion attenuated perturbations of UCPs and ATP contents in adipose tissues and muscle in Ctns −/− mice. 1,25(OH) 2 D 3 suppresses UCPs expression in primary brown adipocyte and suppresses differentiation and mitochondrial respiration of brown adipocyte 1,25(OH) 2 D 3 /VDR by binding to the promoter region of the UCP3 gene and modulating UCP3 gene transcription and subsequent energy metabolism in muscle …”

Section: Discussionmentioning

confidence: 99%

Vitamin D repletion ameliorates adipose tissue browning and muscle wasting in infantile nephropathic cystinosis‐associated cachexia

Cheung

Sheng

Wang

et al. 2019

J cachexia sarcopenia muscle

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Background Ctns−/− mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. Ctns−/− mice are 25(OH)D3 and 1,25(OH)2D3 insufficient. We investigated whether vitamin D repletion could ameliorate adipose tissue browning and muscle wasting in Ctns−/− mice. Methods Twelve‐month‐old Ctns−/− mice and wild‐type controls were treated with 25(OH)D3 and 1,25(OH)2D3 (75 μg/kg/day and 60 ng/kg/day, respectively) or an ethylene glycol vehicle for 6 weeks. Serum chemistry and parameters of energy homeostasis were measured. We quantitated total fat mass and studied expression of molecules regulating adipose tissue browning, energy metabolism, and inflammation. We measured lean mass content, skeletal muscle fibre size, in vivo muscle function (grip strength and rotarod activity), and expression of molecules regulating muscle metabolism. We also analysed the transcriptome of skeletal muscle in Ctns−/− mice using RNAseq. Results Supplementation of 25(OH)D3 and 1,25(OH)2D3 normalized serum concentration of 25(OH)D3 and 1,25(OH)2D3 in Ctns−/− mice, respectively. Repletion of vitamin D partially or fully normalized food intake, weight gain, gain of fat, and lean mass, improved energy homeostasis, and attenuated perturbations of uncoupling proteins and adenosine triphosphate content in adipose tissue and muscle in Ctns−/− mice. Vitamin D repletion attenuated elevated expression of beige adipose cell biomarkers (UCP‐1, CD137, Tmem26, and Tbx1) as well as aberrant expression of molecules implicated in adipose tissue browning (Cox2, Pgf2α, and NF‐κB pathway) in inguinal white adipose tissue in Ctns−/− mice. Vitamin D repletion normalized skeletal muscle fibre size and improved in vivo muscle function in Ctns−/− mice. This was accompanied by correcting the increased muscle catabolic signalling (increased protein contents of IL‐1β, IL‐6, and TNF‐α as well as an increased gene expression of Murf‐2, atrogin‐1, and myostatin) and promoting the decreased muscle regeneration and myogenesis process (decreased gene expression of Igf1, Pax7, and MyoD) in skeletal muscles of Ctns−/− mice. Muscle RNAseq analysis revealed aberrant gene expression profiles associated with reduced muscle and neuron regeneration, increased energy metabolism, and fibrosis in Ctns−/− mice. Importantly, repletion of 25(OH)D3 and 1,25(OH)2D3 normalized the top 20 differentially expressed genes in Ctns−/− mice. Conclusions We report the novel findings that correction of 25(OH)D3 and 1,25(OH)2D3 insufficiency reverses cachexia and may improve quality of life by restoring muscle function in an animal model of infantile nephropathic cystinosis. Mechanistically, vitamin D repletion attenuates adipose tissue browning and muscle wasting in Ctns−/− mice via multiple cellular and molecular mechanisms.

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Section: Discussionmentioning

confidence: 99%

Vitamin D repletion ameliorates adipose tissue browning and muscle wasting in infantile nephropathic cystinosis‐associated cachexia

Cheung

Sheng

Wang

et al. 2019

J cachexia sarcopenia muscle

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“…It is a key hormone involved in calcium and phosphorous balance with several derivatives (Muscogiuri et al, 2017). Vitamin D receptor (VDR) is found in the pancreatic β cells and insulin response tissues such as skeletal muscle and adipose tissue (Fan et al, 2016). Studies showed that vitamin D affected glucose utilization in VDR-dependent manner in muscle and adipose tissue and activated PPARδ, which is a transcription factor involved in fatty acid metabolism (Grammatiki et al, 2017).…”

Section: Vitaminmentioning

confidence: 99%

The Role of Nutrition in the Prevention and Intervention of Type 2 Diabetes

Guo

Huang

Sang

et al. 2020

Front. Bioeng. Biotechnol.

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Type 2 diabetes (T2D) is a rapidly growing epidemic, which leads to increased mortality rates and health care costs. Nutrients (namely, carbohydrates, fat, protein, mineral substances, and vitamin), sensing, and management are central to metabolic homeostasis, therefore presenting a leading factor contributing to T2D. Understanding the comprehensive effects and the underlying mechanisms of nutrition in regulating glucose metabolism and the interactions of diet with genetics, epigenetics, and gut microbiota is helpful for developing new strategies to prevent and treat T2D. In this review, we discuss different mechanistic pathways contributing to T2D and then summarize the current researches concerning associations between different nutrients intake and glucose homeostasis. We also explore the possible relationship between nutrients and genetic background, epigenetics, and metagenomics in terms of the susceptibility and treatment of T2D. For the specificity of individual, precision nutrition depends on the person's genotype, and microbiota is vital to the prevention and intervention of T2D.

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“…1,25-dihydroxyvitamin D3 suppresses expression of UCPs, cell differentiation as well as mitochondrial respiration in brown adipocytes 33,34 . Recent data also confirmed that vitamin D3 modulates UCP3 expression in muscle via the binding site consensus sequences of VDR on the UCP-3 promoter region 35 . Muscle pro-fibrotic factor Transforming growth factor-β1 (TGF-β1) 1.1 ± 1.0 1.1 ± 0.6 3.4 ± 0.4 A,C 1.5 ± 0.4…”

Section: Discussionmentioning

confidence: 64%

Vitamin D ameliorates adipose browning in chronic kidney disease cachexia

Cheung

Ding

Hoffman

et al. 2020

Sci Rep

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Patients with chronic kidney disease (CKD) are often 25(OH)D 3 and 1,25(OH) 2 D 3 insufficient. We studied whether vitamin D repletion could correct aberrant adipose tissue and muscle metabolism in a mouse model of CKD-associated cachexia. Intraperitoneal administration of 25(OH)D 3 and 1,25(OH) 2 D 3 (75 μg/kg/day and 60 ng/kg/day respectively for 6 weeks) normalized serum concentrations of 25(OH)D 3 and 1,25(OH) 2 D 3 in cKD mice. Vitamin D repletion stimulated appetite, normalized weight gain, and improved fat and lean mass content in CKD mice. Vitamin D supplementation attenuated expression of key molecules involved in adipose tissue browning and ameliorated expression of thermogenic genes in adipose tissue and skeletal muscle in cKD mice. Furthermore, repletion of vitamin D improved skeletal muscle fiber size and in vivo muscle function, normalized muscle collagen content and attenuated muscle fat infiltration as well as pathogenetic molecular pathways related to muscle mass regulation in CKD mice. RNAseq analysis was performed on the gastrocnemius muscle. Ingenuity Pathway Analysis revealed that the top 12 differentially expressed genes in CKD were correlated with impaired muscle and neuron regeneration, enhanced muscle thermogenesis and fibrosis. Importantly, vitamin D repletion normalized the expression of those 12 genes in CKD mice. Vitamin D repletion may be an effective therapeutic strategy for adipose tissue browning and muscle wasting in cKD patients. Chronic kidney disease (CKD)-associated cachexia is a complex metabolic disorder that consists of anorexia, weight loss, loss of adipose tissue and muscle mass as well as hypermetabolism 1,2. Current therapies focus on palliation, but calorie supplementation alone is not successful in treating CKD-associated cachexia 3. Brown adipocytes and beige adipocytes, which reside within white adipose tissue (WAT), significantly contribute to whole body energy expenditure 4. Beige adipocytes respond to cold stimulation in a process described as WAT browning 5. We and others have demonstrated the presence of WAT browning in CKD mice 5 amongst other animal disease models of cachexia as well as in patients with cachexia 6-9. We also demonstrated WAT browning in a mouse model of cystinosis, a genetic cause of CKD 10,11. CKD patients have a high prevalence of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 insufficiency 12-14. Vitamin D insufficiency 2,12 may be an important cause of CKD-associated cachexia. Vitamin D influences myogenesis and muscle function 15,16. Furthermore, vitamin D insufficiency has been correlated

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Vitamin D3/VDR resists diet-induced obesity by modulating UCP3 expression in muscles

Cited by 35 publications

References 49 publications

Vitamin D repletion ameliorates adipose tissue browning and muscle wasting in infantile nephropathic cystinosis‐associated cachexia

Vitamin D repletion ameliorates adipose tissue browning and muscle wasting in infantile nephropathic cystinosis‐associated cachexia

The Role of Nutrition in the Prevention and Intervention of Type 2 Diabetes

Vitamin D ameliorates adipose browning in chronic kidney disease cachexia

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