Adipose transplant for inborn errors of branched chain amino acid metabolism in mice.
Adipose transplant for inborn errors of branched chain amino acid metabolism in mice.
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DOI：
10.1016/j.ymgme.2013.05.010
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发表时间：
2013-08
影响因子：
3.8
通讯作者：
Lynch, Christopher J.
中科院分区：
文献类型：
--
作者：
Zimmerman, Heather A.;Olson, Kristine C.;Chen, Gang;Lynch, Christopher J.
关键词：
肝移植似乎对治疗枫红性尿病（MSUD，一种支链氨基酸代谢的遗传性疾病）非常有益;然而，全世界供体肝脏的可用性有限，肝移植的第一年费用相当高。最近的研究表明，完整的脂肪组织，已经广泛用于重建手术，可能有一个被低估的高能力支链氨基酸（BCAA）代谢。在这里，我们研究了脂肪组织移植的潜力，以降低循环支链氨基酸在两个模型的缺陷BCAA代谢，BCATm和PP 2Cm [支链酮酸脱氢酶复合物（BCKDC）磷酸酶]敲除（KO）小鼠。在1-2 g脂肪移植后，BCATm和PP 2Cm KO小鼠在手术后3周增加或维持体重，并且在放血前一周消耗类似或更多的食物/支链氨基酸。将脂肪移植到腹腔中导致无菌炎症反应和不可存活的移植组织。然而，当将1- 2g脂肪皮下移植到背部时，无论是小的（0.1-0.3g）还是用18 ga.与假手术小鼠相比，注射针头后，血浆BCAA降低。在两项关于BCATm KO小鼠的研究和一项关于PP 2Cm KO小鼠的研究中，与未治疗的WT型同胞的基线血浆BCAA浓度相比，脂肪移植导致血浆BCAA降低52-81%。在PP 2Cm KO小鼠中，脂肪移植也显著降低了血浆中的单个BCAA，别异亮氨酸/苯丙氨酸比值也是如此。因此，皮下脂肪移植作为MSUD饮食治疗的辅助治疗可能具有优点。需要进行更多的研究，以进一步完善这一方法。
Liver transplantation appears to be quite beneficial for treatment of Maple Syrup Urine Disease (MSUD, an inherited disorder of branched chain amino acid metabolism); however, there is a limited availability of donor livers worldwide and the first year costs of liver transplants are quite high. Recent studies have suggested that intact adipose tissue, already widely used in reconstructive surgery, may have an underappreciated high capacity for branched chain amino acid (BCAA) metabolism. Here we examined the potential for adipose tissue transplant to lower circulating BCAAs in two models of defective BCAA metabolism, BCATm and PP2Cm [branched chain keto acid dehydrogenase complex (BCKDC) phosphatase] knockout (KO) mice. After 1–2 g fat transplant, BCATm and PP2Cm KO mice gained or maintained body weight 3 weeks after surgery and consumed similar or more food/BCAAs the week before phlebotomy. Transplant of fat into the abdominal cavity led to a sterile inflammatory response and nonviable transplanted tissue. However when 1–2 g of fat was transplanted subcutaneously into the back, either as small (0.1–0.3g) or finely minced pieces introduced with a 18 ga. needle, plasma BCAAs decreased compared to Sham operated mice. In two studies on BCATm KO mice and one study on PP2Cm KO mice, fat transplant led to 52–81% reductions in plasma BCAAs compared to baseline plasma BCAA concentrations of untreated WT type siblings. In PP2Cm KO mice, individual BCAAs in plasma were also significantly reduced by fat transplant, as were the alloisoleucine/Phe ratios. Therefore, subcutaneous fat transplantation may have merit as an adjunct to dietary treatment of MSUD. Additional studies are needed to further refine this approach.
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DOI：
10.1097/med.0b013e328337a81f
发表时间：
2010-04
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
Cypess AM;Kahn CR
通讯作者：
Kahn CR
影响因子：
15.9
作者：
Lu, Gang;Sun, Haipeng;Wang, Yibin
通讯作者：
Wang, Yibin
影响因子：
4.2
作者：
Harris, RA;Joshi, M;Obayashi, M
通讯作者：
Obayashi, M
影响因子：
3.5
作者：
Brunetti-Pierri, Nicola;Lanpher, Brendan;Lee, Brendan
通讯作者：
Lee, Brendan
影响因子：
5.1
作者：
Chuang, DT
通讯作者：
Chuang, DT