A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice.
A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice.
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DOI：
10.1186/s12986-023-00732-5
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发表时间：
2023-02-11
影响因子：
4.5
通讯作者：
Sasaoka, Toshiyasu
中科院分区：
文献类型：
--
作者：
Wada, Tsutomu;Miyazawa, Yuichiro;Ikurumi, Misa;Fuse, Kento;Okekawa, Akira;Onogi, Yasuhiro;Saito, Shigeru;Tsuneki, Hiroshi;Sasaoka, Toshiyasu
MC 903是维生素D3的合成衍生物，旨在减少其对钙代谢的影响，并在临床上用作银屑病的透皮制剂。动物研究表明，口服或腹膜内维生素D3治疗可预防肥胖症的发展。相反，据报道，口服维生素D3的生物利用度在肥胖患者中较低。在目前的研究中，我们的目的是研究MC 903经皮治疗对肥胖小鼠的影响。我们进一步研究了MC 903介导的代谢改善的潜在机制。给雄性C57 BL/6 J小鼠喂食标准食物或60%高脂饮食（HFD）7周，此后开始用MC 903对耳廓进行经皮治疗。在4周治疗期间分析小鼠的代谢谱，并解剖小鼠进行组织学和基因表达分析。在体外使用3 T3-L1脂肪细胞和C2 C12肌管研究MC 903和维生素D3的直接影响。HFD喂养的小鼠显示体重和附睾白色脂肪组织（eWAT）重量显著增加，脂肪细胞增大。他们在eWAT中表现出葡萄糖耐受不良、耗氧量降低和慢性炎症。MC 903的透皮治疗显著改善了HFD喂养小鼠的这些代谢异常，而不影响食物消耗。与增强的能量代谢一致，MC 903处理的HFD小鼠腓肠肌和比目鱼肌中的肌纤维直径和解偶联蛋白3（UCP 3）的表达显著增加。此外，维生素D3和MC 903均抑制3 T3-L1脂肪细胞的脂肪形成分化并增强脂解，并增加培养的C2 C12肌管中UCP 3的表达。此外，MC 903增加了C2 C12肌管的耗氧量，而UCP 3敲低显著降低了它们。MC 903的透皮治疗增加了肌纤维直径和能量代谢，减少了内脏脂肪积累，从而改善了小鼠的肥胖和葡萄糖耐受不良。在线版本包含补充材料，可通过10.1186/s12986-023-00732-5获得。
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. 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. 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. A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice. The online version contains supplementary material available at 10.1186/s12986-023-00732-5.
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影响因子：
5.6
作者：
Crispino M;Trinchese G;Penna E;Cimmino F;Catapano A;Villano I;Perrone-Capano C;Mollica MP
通讯作者：
Mollica MP
影响因子：
4.5
作者：
Agergaard J;Trøstrup J;Uth J;Iversen JV;Boesen A;Andersen JL;Schjerling P;Langberg H
通讯作者：
Langberg H
影响因子：
--
作者：
GASCONBARRE, M;HUET, PM
通讯作者：
HUET, PM
影响因子：
3.2
作者：
Dionne, Serge;Duchatelier, Carl-Frederic;Seidman, Ernest G.
通讯作者：
Seidman, Ernest G.
影响因子：
4.2
作者：
Girgis, Christian M.;Cha, Kuan Minn;Gunton, Jenny E.
通讯作者：
Gunton, Jenny E.