Photobiomodulation (PBM) could improve systemic blood glucose and insulin resistance in diet-induced diabetic mice. A few possible molecular mechanisms for the beneficial effects of PBM on diabetes have been proposed, but there is still an urgent need to explore the underlying mechanisms that support the application of PBM in the treatment of diabetes. Our study aimed to evaluate the effects of PBM on lipid metabolism in the liver of high-fat diet (HFD)-induced mice and explore the potential mechanisms of PBM on obesity and type 2 diabetes. Here, we administered PBM therapy (wavelength: 635 nm, energy density: 8 J/cm²) daily for eight weeks to HFD-induced mice. We detected that eight-week daily administration of PBM ameliorated HFD-induced gain weight, hyperlipidemia, and hyperglycemia, but also protected against diet-induced hepatic steatosis and insulin resistance. Furthermore, PBM increased AMP-activated protein kinase (AMPK) activation, lowered nuclear translocation of sterol regulatory element binding protein 1 (SREBP1), decreased aberrant lipogenesis, and enhanced insulin sensitive in HFD-induced mice livers. We also observed that Ca²⁺/calmodulin-dependent protein kinase kinase β (CaMKKβ) activation was responsible for AMPK activation in insulin-resistant HepG2 cells exposed to PBM. In summary, PBM at 635 nm and 8 J/cm² improved hepatic lipid metabolism and inhibited the development of HFD-induced obesity and type 2 diabetes. Moreover, increased intracellular Ca²⁺ content and CaMKKβ-dependent AMPK activation were possible molecular mechanisms underlying the PBM-induced improvement on obesity and type 2 diabetes.

光生物调节（PBM）可以改善饮食诱导的糖尿病小鼠的全身血糖和胰岛素抵抗。已经提出了几种可能的PBM对糖尿病有益作用的分子机制，但是仍然迫切需要探索支持PBM在糖尿病治疗中应用的潜在机制。我们的研究旨在评估PBM对高脂饮食（HFD）诱导的小鼠肝脏脂质代谢的影响，并探讨PBM对肥胖和2型糖尿病的潜在作用机制。在这里，我们进行了PBM治疗（波长：635 nm，能量密度：8 J / cm ²），每天8周（对HFD诱导的小鼠）。我们检测到，每天服用八周的PBM可以改善HFD引起的体重增加，高脂血症和高血糖，但还可以防止饮食引起的肝脂肪变性和胰岛素抵抗。此外，PBM增加了HF诱导的小鼠肝脏中AMP激活的蛋白激酶（AMPK）激活，降低了固醇调节元件结合蛋白1（SREBP1）的核转运，减少了异常脂肪生成并增强了胰岛素敏感性。我们还观察到，Ca ²⁺ /钙调蛋白依赖性蛋白激酶激酶β（CaMKKβ）激活是暴露于PBM的胰岛素抵抗性HepG2细胞中AMPK激活的原因。总之，PBM在635 nm和8 J / cm ^2下改善肝脂质代谢并抑制HFD诱发的肥胖和2型糖尿病的发展。此外，增加的细胞内Ca ²⁺含量和CaMKKβ依赖性AMPK激活可能是PBM诱导的肥胖症和2型糖尿病改善的潜在分子机制。