Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity.
Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity.
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DOI：
10.1371/journal.pone.0137388
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Reynolds TH 4th
中科院分区：
文献类型：
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作者：
Brestoff JR;Brodsky T;Sosinsky AZ;McLoughlin R;Stansky E;Fussell L;Sheppard A;DiSanto-Rose M;Kershaw EE;Reynolds TH 4th
超氧化物歧化酶模拟锰[III]四[5,10,15,20]-苯甲酸卟啉 (MnTBAP) 是一种有效的抗氧化剂化合物，已被证明可以限制短期高脂肪喂养期间的体重增加，而不会防止胰岛素抵抗。然而，MnTBAP 是否具有治疗已有肥胖和胰岛素抵抗的潜力仍不清楚。为了研究这一点，小鼠在 24 周高脂肪饮食 (HFD) 方案的最后五周接受了 MnTBAP 或载体治疗。 MnTBAP 治疗显着降低了喂食 HFD 和低脂饮食 (LFD) 的小鼠的体重并减少了白色脂肪组织 (WAT) 的质量。肥胖的减少与热量摄入的减少相关，但不会显着改变能量消耗，这表明 MnTBAP 部分通过调节能量平衡来减少肥胖。 MnTBAP 治疗还改善了 HFD 喂养小鼠的胰岛素作用，这是一种与肌肉和 WAT 中蛋白激酶 B (PKB) 磷酸化和表达增加相关的生理反应。由于 MnTBAP 是一种金属卟啉分子，我们假设其促进体重减轻和提高胰岛素敏感性的能力受到血红素加氧酶-1 (HO-1) 的调节，其方式与钴原卟啉类似。尽管 MnTBAP 治疗增加了 HO-1 的表达，但给予有效的 HO-1 抑制剂锡中卟啉 (SnMP) 并没有阻止 MnTBAP 改变热量摄入、肥胖或胰岛素作用的能力，这表明 MnTBAP 独立于 HO-1 影响这些代谢过程。这些数据表明，MnTBAP 可以通过减少热量摄入和增加 PKB 磷酸化和表达来改善已有的肥胖并改善胰岛素作用。
The superoxide dismutase mimetic manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin (MnTBAP) is a potent antioxidant compound that has been shown to limit weight gain during short-term high fat feeding without preventing insulin resistance. However, whether MnTBAP has therapeutic potential to treat pre-existing obesity and insulin resistance remains unknown. To investigate this, mice were treated with MnTBAP or vehicle during the last five weeks of a 24-week high fat diet (HFD) regimen. MnTBAP treatment significantly decreased body weight and reduced white adipose tissue (WAT) mass in mice fed a HFD and a low fat diet (LFD). The reduction in adiposity was associated with decreased caloric intake without significantly altering energy expenditure, indicating that MnTBAP decreases adiposity in part by modulating energy balance. MnTBAP treatment also improved insulin action in HFD-fed mice, a physiologic response that was associated with increased protein kinase B (PKB) phosphorylation and expression in muscle and WAT. Since MnTBAP is a metalloporphyrin molecule, we hypothesized that its ability to promote weight loss and improve insulin sensitivity was regulated by heme oxygenase-1 (HO-1), in a similar fashion as cobalt protoporphyrins. Despite MnTBAP treatment increasing HO-1 expression, administration of the potent HO-1 inhibitor tin mesoporphyrin (SnMP) did not block the ability of MnTBAP to alter caloric intake, adiposity, or insulin action, suggesting that MnTBAP influences these metabolic processes independent of HO-1. These data demonstrate that MnTBAP can ameliorate pre-existing obesity and improve insulin action by reducing caloric intake and increasing PKB phosphorylation and expression.