Lowell B B, S-Susulic V, Hamann A, Lawitts J A, Himms-Hagen J, Boyer B B, Kozak L P, Flier J S
Charles A. Dana Research Institute, Boston, Massachusetts.
Nature. 1993;366(6457):740-2. doi: 10.1038/366740a0.
Brown adipose tissue, because of its capacity for uncoupled mitochondrial respiration, has been implicated as an important site of facultative energy expenditure. This has led to speculation that this tissue normally functions to prevent obesity. Attempts to ablate or denervate brown adipose tissue surgically have been uninformative because it exists in diffuse depots and has substantial capacity for regeneration and hypertrophy. Here we have used a transgenic toxigene approach to create two lines of transgenic mice with primary deficiency of brown adipose tissue. At 16 days, both lines have decreased brown fat and obesity. In one line, brown fat subsequently regenerates and obesity resolves. In the other line, the deficiency persists and obesity, with its morbid complications, advances. Obesity develops in the absence of hyperphagia, indicating that brown fat deficient mice have increased metabolic efficiency. As obesity progresses, transgenic animals develop hyperphagia. This study supports a critical role for brown adipose tissue in the nutritional homeostasis of mice.
棕色脂肪组织因其具有解偶联线粒体呼吸的能力，被认为是适应性能量消耗的重要部位。这引发了一种推测，即该组织通常发挥着预防肥胖的作用。通过手术切除或去除棕色脂肪组织神经的尝试并未提供有用信息，因为它存在于分散的储存部位，并且具有很强的再生和肥大能力。在此，我们采用转基因毒素基因方法创建了两系棕色脂肪组织原发性缺陷的转基因小鼠。在16日龄时，两系小鼠的棕色脂肪均减少且出现肥胖。在其中一系中，棕色脂肪随后再生，肥胖问题得到解决。而在另一系中，缺陷持续存在，肥胖及其相关的病态并发症不断发展。肥胖在无食欲亢进的情况下发生，这表明棕色脂肪缺陷小鼠的代谢效率提高。随着肥胖的进展，转基因动物出现食欲亢进。本研究支持棕色脂肪组织在小鼠营养稳态中起关键作用。
