VA St. Louis Health Care System, St. Louis, Missouri, USA.
Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Obesity (Silver Spring). 2023 Aug;31(8):2065-2075. doi: 10.1002/oby.23799.
In preclinical models, insulin resistance in the dorsal striatum (DS) contributes to overeating. Although human studies support the concept of central insulin resistance, they have not investigated its effect on consummatory reward-induced brain activity.
Taste-induced activation was assessed in the caudate and putamen of the DS with blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Three phenotypically distinct groups were studied: metabolically healthy lean, metabolically healthy obesity, and metabolically unhealthy obesity (MUO; presumed to have central insulin resistance). Participants with MUO also completed a weight loss intervention followed by a second functional magnetic resonance imaging session.
The three groups were significantly different at baseline consistent with the design. The metabolically healthy lean group had a primarily positive BOLD response, the MUO group had a primarily negative BOLD response, and the metabolically healthy obesity group had a response in between the two other groups. Food craving was predicted by taste-induced activation. After weight loss in the MUO group, taste-induced activation increased in the DS.
These data support the hypothesis that insulin resistance and obesity contribute to aberrant responses to taste in the DS, which is only partially attenuated by weight loss. Aberrant responses to food exposure may be a barrier to weight loss.
在临床前模型中,背侧纹状体(DS)的胰岛素抵抗会导致过度进食。尽管人类研究支持中枢胰岛素抵抗的概念,但它们并未研究其对摄食奖励诱导的大脑活动的影响。
采用血氧水平依赖(BOLD)功能磁共振成像技术评估 DS 中的尾状核和壳核的味觉诱导激活。研究了三个表型明显不同的组:代谢健康的瘦组、代谢健康的肥胖组和代谢不健康的肥胖组(MUO;推测存在中枢胰岛素抵抗)。MUO 组的参与者还完成了减肥干预,随后进行了第二次功能磁共振成像检查。
三组在基线时存在显著差异,与设计一致。代谢健康的瘦组表现出主要为正的 BOLD 反应,MUO 组表现出主要为负的 BOLD 反应,而代谢健康的肥胖组的反应介于另外两组之间。食物渴望与味觉诱导的激活有关。在 MUO 组减肥后,DS 中的味觉诱导激活增加。
这些数据支持这样的假设,即胰岛素抵抗和肥胖导致 DS 对味觉的异常反应,而减肥只能部分减轻这种异常反应。对食物暴露的异常反应可能是减肥的障碍。