Noninvasive Dual-Modality Photoacoustic-Ultrasonic Imaging to Detect Mammalian Embryo Abnormalities after Prenatal Exposure to Methylmercury Chloride (MMC): A Mouse Study

Qiu, Qi; Huang, Yali; Zhang, Bei; Huang, Doudou; Chen, Xin; Fan, Zhongxiong; Lin, Jinpei; Yang, Wensheng; Wang, Kai; Qu, Ning; Li, Juan; Li, Zhihong; Huang, Jingyu; Li, Shenrui; Zhang, Jiaxing; Liu, Gang; Rui, Gang; Chen, Xiaoyuan; Zhao, Qingliang

doi:10.1289/ehp8907

Cited by 4 publications

(1 citation statement)

References 94 publications

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“…An echocardiogram was performed as described previously 115,116 . Briefly, mice anaesthetized as in the electrocardiogram were placed in a supine position on a heated (to 37 °C) ultrasound platform to maintain body temperature.…”

Section: Cardiac Function Studiesmentioning

confidence: 99%

The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK

Zhang

Wang

et al. 2022

Nat Metab

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The activity of 5′-adenosine monophosphate-activated protein kinase (AMPK) is inversely correlated with the cellular availability of glucose. When glucose levels are low, the glycolytic enzyme aldolase is not bound to fructose-1,6-bisphosphate (FBP) and, instead, signals to activate lysosomal AMPK. Here, we show that blocking FBP binding to aldolase with the small molecule aldometanib selectively activates the lysosomal pool of AMPK and has beneficial metabolic effects in rodents. We identify aldometanib in a screen for aldolase inhibitors and show that it prevents FBP from binding to v-ATPase-associated aldolase and activates lysosomal AMPK, thereby mimicking a cellular state of glucose starvation. In male mice, aldometanib elicits an insulin-independent glucose-lowering effect, without causing hypoglycaemia. Aldometanib also alleviates fatty liver and nonalcoholic steatohepatitis in obese male rodents. Moreover, aldometanib extends lifespan and healthspan in both Caenorhabditis elegans and mice. Taken together, aldometanib mimics and adopts the lysosomal AMPK activation pathway associated with glucose starvation to exert physiological roles, and might have potential as a therapeutic for metabolic disorders in humans.

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Section: Cardiac Function Studiesmentioning

confidence: 99%