Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
Cytotherapy. 2013 Aug;15(8):971-8. doi: 10.1016/j.jcyt.2013.03.008. Epub 2013 May 31.
Obesity and its associated diseases demand better therapeutic strategies. Regenerative medicine combined with gene therapy has emerged as a promising approach in various clinical applications. Adiponectin (ApN) and its receptors have been demonstrated to play beneficial roles in modulating glucose and lipid homeostasis. In the current study, we tested such an approach by transplanting mesenchymal stromal cells (MSCs) from porcine ApN receptor (pAdipoR) 1-transgenic mice into high-fat/sucrose diet (HFSD)-fed mice.
Twenty 6-week-old Friend virus B/NJNarl male mice were randomly assigned into four groups with the control fed a chow diet (chow) and others HFSD for 10 months. The HFSD groups were then intraperitoneally injected once per week for 8 weeks with placebo (200 μL phosphate-buffered saline), wild-type MSC (WT-MSC, 2 × 10(6) cells/200 μL phosphate-buffered saline) or pAdipoR1-transgenic MSC (pR1-tMSC, 2 × 10(6) cells/200 μL phosphate-buffered saline), respectively. Body weights, blood samples, tissue histology, and gene expression and protein levels of metabolism-associated genes were analyzed.
Both WT-MSC and pR1-tMSC transplantations restored the messenger RNA expression of AdipoR1, with those of glucose transporter 4 and 5'-adenosine monophosphate-activated protein kinase catalytic subunit α-1 and protein levels of pyruvate kinase induced by pR1-tMSC in the muscles of HFSD-fed mice. In the liver, both WT-MSC and pR1-tMSC ameliorated HFSD-induced hepatosteatosis, with the gene expression of lipoprotein lipase and hormone-sensitive lipase upregulated by the latter. Lastly, pR1-tMSC transplantation reduced fatty acid synthase mRNA levels in the adipose tissues of HFSD-fed mice.
This study demonstrates the modulatory actions of MSC and pR1-tMSC on genes associated with glucose and lipid metabolism and provides insights into its therapeutic application for obesity-associated metabolic complication.
肥胖及其相关疾病需要更好的治疗策略。再生医学与基因治疗相结合，已在各种临床应用中崭露头角。脂联素（ApN）及其受体已被证明在调节葡萄糖和脂质稳态方面发挥有益作用。在本研究中，我们通过将猪脂联素受体（pAdipoR）1 转基因小鼠的间充质基质细胞（MSCs）移植到高脂肪/蔗糖饮食（HFSD）喂养的小鼠中，测试了这种方法。
20 只 6 周龄 Friend 病毒 B/NJNarl 雄性小鼠被随机分为 4 组，对照组喂食标准饮食（chow），其余 3 组喂食 HFSD 10 个月。然后，HFSD 组每周腹腔注射一次安慰剂（200 μL 磷酸盐缓冲液）、野生型 MSC（WT-MSC，2×10^6 个细胞/200 μL 磷酸盐缓冲液）或 pAdipoR1 转基因 MSC（pR1-tMSC，2×10^6 个细胞/200 μL 磷酸盐缓冲液），共 8 周。分析体重、血液样本、组织学、代谢相关基因的表达和蛋白水平。
WT-MSC 和 pR1-tMSC 移植均恢复了 HFSD 喂养小鼠肌肉中 AdipoR1 的信使 RNA 表达，WT-MSC 和 pR1-tMSC 诱导葡萄糖转运蛋白 4 和 5'-腺苷一磷酸激活蛋白激酶催化亚基 α-1 的蛋白水平升高。在肝脏中，WT-MSC 和 pR1-tMSC 均改善了 HFSD 诱导的肝脂肪变性，后者上调了脂蛋白脂肪酶和激素敏感脂肪酶的基因表达。最后，pR1-tMSC 移植降低了 HFSD 喂养小鼠脂肪组织中脂肪酸合酶 mRNA 水平。
本研究证明了 MSC 和 pR1-tMSC 对与葡萄糖和脂质代谢相关基因的调节作用，并为其治疗肥胖相关代谢并发症提供了新的见解。
