Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2018 May 10;13(5):e0196743. doi: 10.1371/journal.pone.0196743. eCollection 2018.
Associated with numerous metabolic and behavioral abnormalities, obesity is classified by metrics reliant on body weight (such as body mass index). However, overnutrition is the common cause of obesity, and may independently contribute to these obesity-related abnormalities. Here, we use dietary challenges to parse apart the relative influence of diet and/or energy balance from body weight on various metabolic and behavioral outcomes.
Seventy male mice (mus musculus) were subjected to the diet switch feeding paradigm, generating groups with various body weights and energetic imbalances. Spontaneous activity patterns, blood metabolite levels, and unbiased gene expression of the nutrient-sensing ventral hypothalamus (using RNA-sequencing) were measured, and these metrics were compared using standardized multivariate linear regression models.
Spontaneous activity patterns were negatively related to body weight (p<0.0001) but not diet/energy balance (p = 0.63). Both body weight and diet/energy balance predicted circulating glucose and insulin levels, while body weight alone predicted plasma leptin levels. Regarding gene expression within the ventral hypothalamus, only two genes responded to diet/energy balance (neuropeptide y [npy] and agouti-related peptide [agrp]), while others were related only to body weight.
Collectively, these results demonstrate that individual components of obesity-specifically obesogenic diets/energy imbalance and elevated body mass-can have independent effects on metabolic and behavioral outcomes. This work highlights the shortcomings of using body mass-based indices to assess metabolic health, and identifies novel associations between blood biomarkers, neural gene expression, and animal behavior following dietary challenges.
肥胖与许多代谢和行为异常有关，其分类依据是依赖于体重的指标（如体重指数）。然而，营养过剩是肥胖的常见原因，它可能独立于体重对这些肥胖相关的异常产生影响。在这里，我们使用饮食挑战来分离饮食和/或能量平衡对各种代谢和行为结果的相对影响，而不是依赖于体重。
70 只雄性小鼠（mus musculus）接受饮食转换喂养范式，产生了具有不同体重和能量失衡的组。测量自发活动模式、血液代谢物水平以及营养感应腹侧下丘脑的无偏基因表达（使用 RNA 测序），并使用标准化多元线性回归模型比较这些指标。
自发活动模式与体重呈负相关（p<0.0001），但与饮食/能量平衡无关（p = 0.63）。体重和饮食/能量平衡均预测循环葡萄糖和胰岛素水平，而仅体重预测血浆瘦素水平。关于腹侧下丘脑内的基因表达，只有两种基因对饮食/能量平衡有反应（神经肽 Y [NPY]和刺鼠相关肽 [AGRP]），而其他基因仅与体重有关。
总的来说，这些结果表明肥胖的个体成分-具体而言，致肥胖饮食/能量失衡和体重增加-可以对代谢和行为结果产生独立的影响。这项工作突出了使用基于体重的指数来评估代谢健康的缺点，并确定了饮食挑战后血液生物标志物、神经基因表达与动物行为之间的新关联。
