A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice
Abstract Aim MC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesit...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Nutrition & Metabolism |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12986-023-00732-5 |
| _version_ | 1811166074687717376 |
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| author | Tsutomu Wada Yuichiro Miyazawa Misa Ikurumi Kento Fuse Akira Okekawa Yasuhiro Onogi Shigeru Saito Hiroshi Tsuneki Toshiyasu Sasaoka |
| author_facet | Tsutomu Wada Yuichiro Miyazawa Misa Ikurumi Kento Fuse Akira Okekawa Yasuhiro Onogi Shigeru Saito Hiroshi Tsuneki Toshiyasu Sasaoka |
| author_sort | Tsutomu Wada |
| collection | DOAJ |
| description | Abstract Aim MC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement. Materials and methods Male C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Results HFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes. Conclusions A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice. |
| first_indexed | 2024-04-10T15:46:37Z |
| format | Article |
| id | doaj.art-9ed377457e1f4006b28345ea952e8bfc |
| institution | Directory Open Access Journal |
| issn | 1743-7075 |
| language | English |
| last_indexed | 2024-04-10T15:46:37Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Nutrition & Metabolism |
| spelling | doaj.art-9ed377457e1f4006b28345ea952e8bfc2023-02-12T12:06:07ZengBMCNutrition & Metabolism1743-70752023-02-0120111610.1186/s12986-023-00732-5A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in miceTsutomu Wada0Yuichiro Miyazawa1Misa Ikurumi2Kento Fuse3Akira Okekawa4Yasuhiro Onogi5Shigeru Saito6Hiroshi Tsuneki7Toshiyasu Sasaoka8Department of Clinical Pharmacology, University of ToyamaDepartment of Clinical Pharmacology, University of ToyamaDepartment of Clinical Pharmacology, University of ToyamaDepartment of Clinical Pharmacology, University of ToyamaDepartment of Clinical Pharmacology, University of ToyamaDepartment of Clinical Pharmacology, University of ToyamaDepartment of Obstetrics and Gynecology, University of ToyamaDepartment of Clinical Pharmacology, University of ToyamaDepartment of Clinical Pharmacology, University of ToyamaAbstract Aim MC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement. Materials and methods Male C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Results HFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes. Conclusions A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice.https://doi.org/10.1186/s12986-023-00732-5CalcipotriolMyotubeObesityTransdermal treatmentUncoupling protein 3 (UCP3) |
| spellingShingle | Tsutomu Wada Yuichiro Miyazawa Misa Ikurumi Kento Fuse Akira Okekawa Yasuhiro Onogi Shigeru Saito Hiroshi Tsuneki Toshiyasu Sasaoka A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice Nutrition & Metabolism Calcipotriol Myotube Obesity Transdermal treatment Uncoupling protein 3 (UCP3) |
| title | A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice |
| title_full | A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice |
| title_fullStr | A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice |
| title_full_unstemmed | A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice |
| title_short | A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice |
| title_sort | transdermal treatment with mc903 ameliorates diet induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice |
| topic | Calcipotriol Myotube Obesity Transdermal treatment Uncoupling protein 3 (UCP3) |
| url | https://doi.org/10.1186/s12986-023-00732-5 |
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