Rhee S D, Sung Y Y, Lee Y S, Kim J Y, Jung W H, Kim M J, Lee M-S, Lee M K, Yang S-D, Cheon H G
Center for Metabolic Syndrome Therapeutics, Korea Research Institute of Chemical Technology, Daejon, Korea.
Exp Clin Endocrinol Diabetes. 2011 Apr;119(4):243-51. doi: 10.1055/s-0030-1267202. Epub 2010 Oct 28.
TALLYHO/JngJ (TallyHo) mouse is a recently established animal model for type 2 diabetes mellitus (T2DM) with phenotypes of mild obesity and male-limited hyperglycemia. In this study, we investigated how obesity develops in TallyHo mice by measuring parameters of food intake and energy expenditure. At 4 weeks of age, TallyHo mice were heavier than control C57BL/6 mice with increased food intake but comparable energy expenditure parameters, such as body temperature, cold-induced thermogenesis, oxygen consumption rate (VO(2)) and spontaneous locomotor activity. Furthermore, pair-fed TallyHo mice, which were fed the same amount of food as C57BL/6 mice, showed similar patterns of body weight gain to C57BL/6 mice at all ages, implying that obesity in TallyHo mice may develop by increased food intake but not by decreased energy consumption. TallyHo mice appear to have hypothalamic leptin resistance at 4 weeks of age, as indicated by the increased expression of orexigenic neuropeptides in the hypothalamus and no alteration of food intake and neuropeptide expression upon intravenous leptin treatment. Leptin injection to TallyHo mice, however, increased the phosphorylation of STAT3 and Akt, an important signaling mediator of leptin, in a pattern similar to that in C57BL/6 mice. In conclusion, increased food intake is a crucial component in the development of obesity in TallyHo mice, in which central leptin resistance, possibly caused by uncoupling between activation of leptin signaling and neuropeptide expression, might be involved.
TALLYHO/JngJ（TallyHo）小鼠是一种最近建立的2型糖尿病（T2DM）动物模型，具有轻度肥胖和雄性特异性高血糖的表型。在本研究中，我们通过测量食物摄入量和能量消耗参数来研究TallyHo小鼠肥胖的发展情况。4周龄时，TallyHo小鼠比对照C57BL/6小鼠重，食物摄入量增加，但能量消耗参数相当，如体温、冷诱导产热、耗氧率（VO₂）和自发运动活动。此外，与C57BL/6小鼠喂食相同量食物的配对喂养TallyHo小鼠在所有年龄段体重增加模式与C57BL/6小鼠相似，这意味着TallyHo小鼠的肥胖可能是由食物摄入量增加而非能量消耗减少引起的。4周龄时，TallyHo小鼠似乎存在下丘脑瘦素抵抗，表现为下丘脑促食欲神经肽表达增加，静脉注射瘦素后食物摄入量和神经肽表达无变化。然而，给TallyHo小鼠注射瘦素会增加STAT3和Akt（瘦素的重要信号传导介质）的磷酸化，其模式与C57BL/6小鼠相似。总之，食物摄入量增加是TallyHo小鼠肥胖发展的关键因素，其中可能涉及由瘦素信号激活与神经肽表达解偶联导致的中枢瘦素抵抗。
