Pagliassotti M J, Gayles E C, Hill J O
Department of Pediatrics, University of Colorado Health Sciences Center, Denver 80262, USA.
Ann N Y Acad Sci. 1997 Sep 20;827:431-48. doi: 10.1111/j.1749-6632.1997.tb51853.x.
In summary, an imbalance between energy intake and energy expenditure can explain approximately 80% of the variance in body weight gain in this dietary model of obesity. Several metabolic variables appear to contribute to differences in energy balance. A high RQ and an inappropriate suppression of glucose production by insulin appear to be linked to the increase in energy intake that occurs when obesity-prone rats are provided with the high-fat diet. In addition, early tissue enzymatic differences in obesity-prone versus obesity-resistant rats may contribute to differences in energy expenditure and/or to differences in nutrient partitioning. In this dietary model, susceptibility to dietary obesity involves a metabolic environment that includes a high RQ and a reduced ability of insulin to suppress glucose appearance (FIG. 9). However, this environment does not lead to obesity nor to a measurable difference in body weight gain when the susceptible rats are eating a low-fat diet. The high-fat diet is a necessary catalyst for the observed variability in body weight gain and the development of obesity. As a catalyst, the high-fat diet results in an imbalance between energy intake and energy expenditure in some, but not all, rats. This imbalance interacts with the permissive metabolic environment (tissue enzymatic profile favoring carbohydrate utilization and lipid storage) to produce obesity on the high-fat diet. Later, in the HFD feeding period, the rate of weight gain is not significantly different between OP and OR rats, although net fat accumulation remains greater in the former group. It is interesting that this later period is characterized by a reduction in the difference in both RQ and energy intake between OP and OR rats. Thus, during the later stages of HFD feeding, the discrepancy in both energy balance and nutrient balance between OP and OR rats is reduced. This dietary model of obesity is relevant to human obesity. While the prevalence of obesity is high, the majority of people are not obese. The high prevalence of obesity may be due to environmental catalysts that interact with inherent behavioral and metabolic characteristics that favor nutrient retention. Resistance to obesity can be achieved by avoiding these environmental catalysts, by having inherent characteristics that prevent nutrient retention, or both. Our work suggests that the complete understanding of obesity will require not only the identification and functional significance of the genes that determine the inherent capacity of the behavioral and metabolic systems, but also the role of environmental catalysts in determining where and how these systems operate.
总之，在这种肥胖饮食模型中，能量摄入与能量消耗之间的失衡可解释约80%的体重增加差异。几个代谢变量似乎导致了能量平衡的差异。高呼吸商（RQ）以及胰岛素对葡萄糖生成的不适当抑制，似乎与易肥胖大鼠食用高脂饮食时能量摄入的增加有关。此外，易肥胖大鼠与抗肥胖大鼠早期的组织酶差异，可能导致能量消耗的差异和/或营养分配的差异。在这种饮食模型中，对饮食性肥胖的易感性涉及一种代谢环境，其特征包括高呼吸商以及胰岛素抑制葡萄糖生成的能力降低（图9）。然而，当易感性大鼠食用低脂饮食时，这种环境既不会导致肥胖，也不会导致体重增加出现可测量的差异。高脂饮食是观察到的体重增加变异性和肥胖发展的必要催化剂。作为一种催化剂，高脂饮食在一些（但不是所有）大鼠中导致能量摄入与能量消耗之间的失衡。这种失衡与允许性代谢环境（有利于碳水化合物利用和脂质储存的组织酶谱）相互作用，从而在高脂饮食时产生肥胖。后来，在高脂饮食喂养期，易肥胖（OP）大鼠和抗肥胖（OR）大鼠的体重增加速率没有显著差异，尽管前一组的净脂肪积累仍然更多。有趣的是，在这个后期阶段，OP大鼠和OR大鼠之间的呼吸商和能量摄入差异都有所减小。因此，在高脂饮食喂养的后期阶段，OP大鼠和OR大鼠之间的能量平衡和营养平衡差异都减小了。这种肥胖饮食模型与人类肥胖相关。虽然肥胖的患病率很高，但大多数人并不肥胖。肥胖的高患病率可能是由于环境催化剂与有利于营养保留的固有行为和代谢特征相互作用所致。通过避免这些环境催化剂、具有防止营养保留的固有特征或两者兼而有之，可以实现对肥胖的抗性。我们的研究表明，对肥胖的全面理解不仅需要确定决定行为和代谢系统固有能力的基因及其功能意义，还需要了解环境催化剂在确定这些系统在何处以及如何运作方面的作用。
