Excessive circulating free fatty acids (FFA) cause insulin resistance in peripheral tissues by inhibiting the proximal insulin signaling pathway. White adipose tissue (WAT) is a primary source of FFA generation and release through triglyceride (TG) hydrolysis. Thus, reducing excessive lipolysis in adipocytes ameliorates whole-body insulin resistance in type 2 diabetes. Here, we found that a noninvasive photobiomodulation therapy (PBMT), decreased FFA generation and release in WATs from high-fat diet (HFD)-fed mice and diabetic db/db mice. Meanwhile, plasma FFA and TG levels were reduced in two mouse models after PBMT. PBMT promoted mitochondrial reactive oxygen species (ROS) generation, which inhibited phosphatase and tensin homologue (PTEN) and promoted protein kinase B (AKT) activation. Photoactivation of AKT inhibited the transcriptional activity of Forkhead box transcription factor O1 (FoxO1), reducing expression of lipolytic enzymes and FFA generation and release. Eliminating ROS elimination or inhibiting AKT blocked the effects of the laser therapy in vivo and in vitro. Taken together, PBMT suppresses FFA generation and release in insulin-resistant adipocytes, contributing to improvement of insulin resistance in mouse models of type 2 diabetes.

中文翻译：

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光生物调节疗法减少了2型糖尿病中游离脂肪酸的产生和在脂肪细胞中的释放，从而改善了胰岛素抵抗。

过多的循环游离脂肪酸（FFA）通过抑制近端胰岛素信号传导途径，导致周围组织的胰岛素抵抗。白色脂肪组织（WAT）是FFA产生并通过甘油三酸酯（TG）水解释放的主要来源。因此，减少脂肪细胞中过多的脂解改善了2型糖尿病的全身胰岛素抵抗。在这里，我们发现无创光生物调节疗法（PBMT）可以减少FFA的产生和从高脂饮食（HFD）喂养的小鼠和糖尿病db / db小鼠的WAT中释放。同时，在PBMT后的两种小鼠模型中血浆FFA和TG水平降低。PBMT促进线粒体活性氧（ROS）生成，从而抑制磷酸酶和张力蛋白同源物（PTEN），并促进蛋白激酶B（AKT）活化。AKT的光活化抑制了叉头盒转录因子O1（FoxO1）的转录活性，减少了脂解酶的表达以及FFA的产生和释放。消除ROS消除或抑制AKT可以在体内和体外阻断激光治疗的效果。综上所述，PBMT可抑制FFA的产生和在胰岛素抵抗性脂肪细胞中的释放，从而有助于改善2型糖尿病小鼠模型的胰岛素抵抗。