MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0SL, UK.
University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust‑MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0SL, UK.
Sci Rep. 2021 Sep 2;11(1):17571. doi: 10.1038/s41598-021-96278-8.
Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.
神经元钙黏蛋白 (Nnat) 先前被报道为染色质调节因子 Trim28 下游印迹基因网络的一部分。Trim28 或该网络的成员（包括神经元钙黏蛋白）的破坏会导致一种不寻常的体重双峰表型。为了更好地描述这种可变性，我们检查了携带父本缺失等位基因且不表达 Nnat 的 Nnat 缺失小鼠中能量平衡的关键贡献者。与我们之前的研究一致，在 Chow 饮食下，Nnat 缺乏的小鼠表现出双峰体重表型，超过 30%的 Nnat 小鼠发生肥胖。在 45%高脂肪饮食和暴露于热中性（30°C）的情况下，Nnat 缺乏的小鼠保持了高可变性的体重表型。在代谢测定系统中，Nnat 小鼠的食物摄入量高度可变，一些小鼠的摄入量是野生型同窝仔鼠的两倍以上。Nnat 小鼠还在第二个非家庭笼环境中出现了过度进食反应。体重和能量消耗之间存在预期的相关性，但对于正能量平衡和体重的影响进行校正后，神经元钙黏蛋白缺乏对能量消耗的影响大大降低。雄性和雌性 Nnat 小鼠在体重表型和食物摄入量的变异性程度上显示出细微差异，Nnat 小鼠下丘脑基因表达的不同模式进一步反映了性别二态性。失活印迹基因 Nnat 与高度可变的食物摄入量相关，这种表型的影响在遗传上相同的个体之间存在差异。
