Park Seongjoon, Komatsu Toshimitsu, Hayashi Hiroko, Mori Ryoichi, Shimokawa Isao
Department of Pathology, Nagasaki University School of Medicine, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Biomedicines. 2021 Nov 22;9(11):1739. doi: 10.3390/biomedicines9111739.
Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), which is initiated by adipocyte-macrophage crosstalk. Among the possible molecules regulating this crosstalk, we focused on neuropeptide Y (NPY), which is known to be involved in hypothalamic appetite and adipose tissue inflammation and metabolism. In this study, the NPY mice showed a marked decrease in body weight and adiposity, and lower free fatty acid and adipose inflammation without food intake alteration during a high fat diet (HFD). Moreover, NPY deficiency increased the thermogenic genes expression in brown adipose tissue. Notably, NPY-mRNA expression was upregulated in macrophages from the HFD mice compared to that from the mice on a standard diet. The NPY-mRNA expression also positively correlated with the liver mass/body weight ratio. NPY deletion alleviated HFD-induced adipose inflammation and liver steatosis. Hence, our findings point toward a novel intracellular mechanism of NPY in the regulation of adipocyte-macrophage crosstalk and highlight NPY antagonism as a promising target for therapeutic approaches against obesity and NAFLD.
肥胖与非酒精性脂肪性肝病（NAFLD）风险增加相关，NAFLD由脂肪细胞与巨噬细胞的相互作用引发。在调节这种相互作用的可能分子中，我们聚焦于神经肽Y（NPY），已知其参与下丘脑食欲以及脂肪组织炎症和代谢。在本研究中，NPY基因敲除小鼠体重和肥胖程度显著降低，游离脂肪酸水平降低，脂肪炎症减轻，且在高脂饮食（HFD）期间食物摄入量未改变。此外，NPY缺乏增加了棕色脂肪组织中产热基因的表达。值得注意的是，与标准饮食小鼠相比，HFD小鼠巨噬细胞中NPY - mRNA表达上调。NPY - mRNA表达也与肝脏质量/体重比呈正相关。NPY缺失减轻了HFD诱导的脂肪炎症和肝脏脂肪变性。因此，我们的研究结果指向了NPY在调节脂肪细胞 - 巨噬细胞相互作用中的一种新的细胞内机制，并突出了NPY拮抗作用作为对抗肥胖和NAFLD治疗方法的一个有前景的靶点。
