Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity.
Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity.
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DOI：
10.1038/s41598-021-96278-8
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发表时间：
2021-09-02
影响因子：
4.6
通讯作者：
Coll AP
中科院分区：
文献类型：
--
作者：
Cimino I;Rimmington D;Tung YCL;Lawler K;Larraufie P;Kay RG;Virtue S;Lam BYH;Fagnocchi L;Ma MKL;Saudek V;Zvetkova I;Vidal-Puig A;Yeo GSH;Farooqi IS;Pospisilik JA;Gribble FM;Reimann F;O'Rahilly S;Coll AP
神经肽（Nnat）以前曾被报道是染色质调节因子Trim 28下游印迹基因网络的一部分。Trim 28或该网络的成员（包括neuronatin）的破坏导致双峰体重的不寻常表型。为了更好地解释这种变异性，我们研究了携带父本无效等位基因且不表达Nnat的Nnat+/−p小鼠中能量平衡的关键因素。与我们之前的研究一致，Nnat缺陷小鼠在食物饮食中表现出双峰体重表型，超过30%的Nnat+/−p小鼠出现肥胖。响应于45%高脂肪饮食和暴露于热中性（30 °C），Nnat缺陷小鼠维持高变体重表型。在量热系统中，Nnat+/−p小鼠的食物摄入量是高度可变的，一些小鼠的摄入量是野生型同窝小鼠的两倍多。在第二个非家庭笼环境中的Nnat+/−p小鼠中也观察到了吞噬反应。体重和能量消耗之间存在预期的相关性，但对正能量平衡和体重影响的校正大大降低了神经元素缺乏对能量消耗的影响。雄性和雌性Nnat+/−p小鼠在体重表型和食物摄入的变异程度上表现出细微的差异，进一步的性二态性反映在Nnat+/−p小鼠下丘脑基因表达的不同模式中。印记基因Nnat的丢失与高度可变的食物摄入量相关，这种表型的影响在遗传相同的个体之间变化。
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+/−p 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+/−p 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+/−p 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+/−p 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+/−p 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+/−p 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.
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DOI：
10.1111/gbb.12679
发表时间：
2020-09
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
通讯作者：
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
2.5
作者：
Dent, C. L.;Humby, T.;Isles, A. R.
通讯作者：
Isles, A. R.
影响因子：
7.2
作者：
Barlow, Denise P.;Bartolomei, Marisa S.
通讯作者：
Bartolomei, Marisa S.
影响因子：
5.2
作者：
Lin, Hsuan-Hwai;Bell, Esther;Uwanogho, Dafe;Perfect, Leo W.;Noristani, Harun;Bates, Thomas J. D.;Snetkov, Vladimir;Price, Jack;Sun, Yuh-Man
通讯作者：
Sun, Yuh-Man