為了在嚴(yán)酷環(huán)境中生存,線蟲的幼蟲能進(jìn)入一種所謂的“多爾(dauer)”狀態(tài),,在處于這種狀態(tài)期間,,它們不吃東西,但仍能活動(dòng),,對(duì)壓力具有抵抗力,,而且極為長壽。
在一個(gè)典型的“多爾”幼蟲體內(nèi),,胰島素類信號(hào)作用減少,,營養(yǎng)儲(chǔ)備充分,而且其代謝過程發(fā)生全面變化,。Patrick Narbonne 和 Richard Roy發(fā)現(xiàn),,如果沒有AMPK (LKB1)信號(hào)作用,“多爾”幼蟲會(huì)迅速耗盡其所儲(chǔ)存的能量,,并且會(huì)由于重要器官衰竭而過早死亡,。在一個(gè)正常的“多爾”幼蟲中,LKB1/AMPK通過減慢甘油三酸酯的水解來保證幼蟲不需要食物而能長壽和具有活力,,從而使體內(nèi)所存儲(chǔ)的脂肪能夠維持更長時(shí)間,,同時(shí)保持正確的滲透調(diào)節(jié)(osmoregulation)。這項(xiàng)工作觸及在關(guān)于衰老,、糖尿病和肥胖癥研究中所涉及的體系,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 457, 210-214 (8 January 2009) | doi:10.1038/nature07536
Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival
Patrick Narbonne1 & Richard Roy1
1 Department of Biology, McGill University, Montréal, Québec H3A 1B1, Canada
Many organisms can enter a dormant state or diapause to survive harsh environmental conditions for extended durations. When Caenorhabditis elegans larvae enter dauer they arrest feeding but remain active and motile, yet become stress-resistant, extremely long-lived and non-ageing1. Entry into dauer is associated with a reduction in insulin-like signalling, the accumulation of nutritive resources and a concomitant global change in metabolism2, 3, 4, 5, yet the precise molecular and physiological processes that enable long-term survival in the absence of caloric intake remain largely unknown. We show here that C. elegans larvae that lack LKB1/AMPK (AMP-activated protein kinase) signalling enter dauer normally, but then rapidly consume their stored energy and prematurely expire following vital organ failure. We found that this signalling pathway acts in adipose-like tissues to downregulate triglyceride hydrolysis so that these lipid reserves are rationed to last the entire duration of the arrest. Indeed, the downregulation of adipose triglyceride lipase (ATGL-1) activity suppresses both the rapid depletion of stored lipids and reduced life span of AMPK mutant dauers, while AMPK directly phosphorylates ATGL-1. Finally, we show that the slow release of energy during dauer is critical for appropriate long-term osmoregulation, which fails as triglyceride resources become depleted. These mechanisms may be essential for survival through diapause, hibernation, or long-term fasting in diverse organisms and may also underlie AMPK-dependent life span extension.