Strain-specific metabolic responses to long-term caloric restriction in female ILSXISS recombinant inbred mice.
Strain-specific metabolic responses to long-term caloric restriction in female ILSXISS recombinant inbred mice.
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DOI：
10.1016/j.mce.2021.111376
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发表时间：
2021-09-15
影响因子：
4.1
通讯作者：
Selman C
中科院分区：
文献类型：
--
作者：
Mulvey L;Wilkie SE;Borland G;Griffiths K;Sinclair A;McGuinness D;Watson DG;Selman C
遗传背景在生物体对热量限制（CR）等干预措施的反应中可能发挥的作用未得到充分重视，但可能很重要。我们研究了遗传背景对雌性重组近交系ILSXISS小鼠品系的一系列代谢参数的影响，这些小鼠品系先前报道对40% CR表现出不同的寿命响应（TejJ 89-寿命延长; TejJ 48-寿命不受影响; TejJ 114-寿命缩短）。在40% CR 10个月后，所有品系的体重均降低，尽管TejJ 114的这种损失（相对于自由采食对照）大于其他品系。在40% CR后，所有品系的性腺白色脂肪组织（gWAT）质量均类似地降低，但棕色脂肪组织（BAT）质量仅在品系TejJ 89和TejJ 48中增加。令人惊讶的是，在TejJ 114中，CR最显著地改善了葡萄糖耐量，而两种菌株TejJ 89和TejJ 114在CR后相对于其AL对照是高胰岛素血症的。随后，我们在AL和40%CR条件下对来自TejJ 89和TejJ 114品系小鼠的gWAT和BAT组织进行了无偏倚的代谢组学方法。在来自TejJ 89的gWAT中，在40% CR后观察到几种长链不饱和脂肪酸的显著减少，但来自TejJ 114的gWAT似乎对CR相对无反应，代谢物变化少得多。BAT内的磷脂酰乙醇胺脂质在TejJ 89 CR后通常升高，而一些磷脂酰甘油脂质降低。然而，来自菌株TejJ 114的BAT再次表现出对CR无反应。这些数据强调了ILSXISS小鼠在40% CR后存在的品系特异性代谢差异。我们认为，正是不同的脂肪库如何动态响应CR可能是一个重要因素，在这些小鼠的可变寿命低于40% CR报告。ILSXISS小鼠在CR后的寿命显示出品系特异性变化。增强葡萄糖稳态与CR下报告的寿命无关。CR下的寿命缩短与WAT和BAT相对无反应相关。脂肪库对CR的反应可能有助于解释ILSXISS小鼠的寿命差异。
The role that genetic background may play in the responsiveness of organisms to interventions such as caloric restriction (CR) is underappreciated but potentially important. We investigated the impact of genetic background on a suite of metabolic parameters in female recombinant inbred ILSXISS mouse strains previously reported to show divergent lifespan responses to 40% CR (TejJ89-lifespan extension; TejJ48-lifespan unaffected; TejJ114-lifespan shortening). Body mass was reduced across all strains following 10 months of 40% CR, although this loss (relative to ad libitum controls) was greater in TejJ114 relative to the other strains. Gonadal white adipose tissue (gWAT) mass was similarly reduced across all strains following 40% CR, but brown adipose tissue (BAT) mass increased only in strains TejJ89 and TejJ48. Surprisingly, glucose tolerance was improved most notably by CR in TejJ114, while both strains TejJ89 and TejJ114 were hyperinsulinemic following CR relative to their AL controls. We subsequently undertook an unbiased metabolomic approach in gWAT and BAT tissue derived from strains TejJ89 and TejJ114 mice under AL and 40% CR. In gWAT from TejJ89 a significant reduction in several long chain unsaturated fatty acids was observed following 40% CR, but gWAT from TejJ114 appeared relatively unresponsive to CR with far fewer metabolites changing. Phosphatidylethanoloamine lipids within the BAT were typically elevated in TejJ89 following CR, while some phosphatidylglycerol lipids were decreased. However, BAT from strain TejJ114 again appeared unresponsive to CR. These data highlight strain-specific metabolic differences exist in ILSXISS mice following 40% CR. We suggest that precisely how different fat depots respond dynamically to CR may be an important factor in the variable longevity under 40% CR reported in these mice. ILSXISS mice show strain-specific variation in longevity following CR. Enhanced glucose homeostasis did not correlate with reported longevity under CR. Shortened lifespan under CR was associated with relatively unresponsive WAT and BAT. How fat depots respond to CR may help explain lifespan differences in ILSXISS mice.
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影响因子：
64.5
作者：
Fontana L;Partridge L
通讯作者：
Partridge L
影响因子：
5.3
作者：
Hulbert, A. J.;Faulks, Sally C.;Buffenstein, Rochelle
通讯作者：
Buffenstein, Rochelle
影响因子：
4.8
作者：
Forster, MJ;Morris, P;Sohal, RS
通讯作者：
Sohal, RS
影响因子：
4.1
作者：
Hoffman JM;Valencak TG
通讯作者：
Valencak TG
DOI：
10.1093/gerona/61.10.1009
发表时间：
2006-10-01
影响因子：
5.1
作者：
Hulbert, A. J.;Faulks, Sally C.;Buffenstein, Rochelle
通讯作者：
Buffenstein, Rochelle