Friend Danielle M, Devarakonda Kavya, O'Neal Timothy J, Skirzewski Miguel, Papazoglou Ioannis, Kaplan Alanna R, Liow Jeih-San, Guo Juen, Rane Sushil G, Rubinstein Marcelo, Alvarez Veronica A, Hall Kevin D, Kravitz Alexxai V
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA.
Section of Molecular Neurobiology, Eunice Shriver Kennedy National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda MD 20892, USA.
Cell Metab. 2017 Feb 7;25(2):312-321. doi: 10.1016/j.cmet.2016.12.001. Epub 2016 Dec 29.
Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring G signaling in these neurons increased activity in obese mice. Surprisingly, although mice with low D2Rs were less active, they were not more vulnerable to diet-induced weight gain than control mice. We conclude that deficits in striatal D2R signaling contribute to physical inactivity in obesity, but inactivity is more a consequence than a cause of obesity.
肥胖与缺乏身体活动有关，而这又会加剧体重增加对健康造成的影响。然而，介导这种关联的机制尚不清楚。我们推测多巴胺信号传导缺陷会导致肥胖个体缺乏身体活动。为了对此进行研究，我们对瘦小鼠和肥胖小鼠多巴胺信号传导的多个方面进行了量化。我们发现，肥胖小鼠纹状体中的D2型受体（D2R）结合减少，但D1型受体结合或多巴胺水平并未降低。从纹状体中等棘状神经元中基因去除D2R足以降低瘦小鼠的运动活性，而恢复这些神经元中的G信号传导则可增加肥胖小鼠的活性。令人惊讶的是，尽管D2R水平低的小鼠活动较少，但它们并不比对照小鼠更容易因饮食导致体重增加。我们得出结论，纹状体D2R信号传导缺陷会导致肥胖个体缺乏身体活动，但缺乏身体活动更多是肥胖的结果而非原因。
