Lackey Denise E, Lazaro Raul G, Li Pingping, Johnson Andrew, Hernandez-Carretero Angelina, Weber Natalie, Vorobyova Ivetta, Tsukomoto Hidekazu, Osborn Olivia
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California.
Southern California Research Center for ALPD and Cirrhosis and Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; and.
Am J Physiol Endocrinol Metab. 2016 Dec 1;311(6):E989-E997. doi: 10.1152/ajpendo.00323.2016. Epub 2016 Nov 1.
Consumption of excess calories results in obesity and insulin resistance and has been intensively studied in mice and humans. The objective of this study was to determine the specific contribution of dietary fat rather than total caloric intake to the development of obesity-associated insulin resistance. We used an intragastric feeding method to overfeed excess calories from a low-fat diet (and an isocalorically matched high-fat diet) through a surgically implanted gastric feeding tube to generate obesity in wild-type mice followed by hyperinsulinemic-euglycemic clamp studies to assess the development of insulin resistance. We show that overfeeding a low-fat diet results in levels of obesity similar to high-fat diet feeding in mice. However, despite a similar body weight, obese high-fat diet-fed mice are more insulin resistant than mice fed an isocaloric low-fat diet. Therefore, increased proportion of calories from dietary fat further potentiates insulin resistance in the obese state. Furthermore, crossover diet studies revealed that reduction in dietary fat composition improves glucose tolerance in obesity. In the context of the current obesity and diabetes epidemic, it is particularly important to fully understand the role of dietary macronutrients in the potentiation and amelioration of disease.
摄入过多热量会导致肥胖和胰岛素抵抗，并且已经在小鼠和人类中进行了深入研究。本研究的目的是确定膳食脂肪而非总热量摄入对肥胖相关胰岛素抵抗发展的具体作用。我们采用胃内喂养方法，通过手术植入的胃饲管，从低脂饮食（以及等热量匹配的高脂饮食）中过量喂食多余热量，以使野生型小鼠肥胖，随后进行高胰岛素-正常血糖钳夹研究，以评估胰岛素抵抗的发展。我们发现，过量喂食低脂饮食会使小鼠的肥胖程度与高脂饮食喂养相似。然而，尽管体重相似，但高脂饮食喂养的肥胖小鼠比等热量低脂饮食喂养的小鼠更具胰岛素抵抗性。因此，膳食脂肪热量比例的增加会进一步增强肥胖状态下的胰岛素抵抗。此外，交叉饮食研究表明，减少膳食脂肪组成可改善肥胖状态下的葡萄糖耐量。在当前肥胖和糖尿病流行的背景下，充分了解膳食宏量营养素在疾病的加重和改善中的作用尤为重要。
