In healthy humans, ammonia circulates in the bloodstream at a concentration around 11–32 μmol/L. Whether ammonia plays any physiological role has been unknown until a recent report published in Nature Metabolism.1 A...In healthy humans, ammonia circulates in the bloodstream at a concentration around 11–32 μmol/L. Whether ammonia plays any physiological role has been unknown until a recent report published in Nature Metabolism.1 Ammonia, long thought to be a toxic waste product of amino acid metabolism, needs to be excreted from the human body as urea. Intriguingly, in this paper, Cheng et al1 for the first time reported that ammonia is not a waste product;rather, it is an unprecedented signaling molecule tying glucose and glutamine to lipid production in human cells. This study revealed that ammonia released from glutamine triggers a cascade of cellular processes leading to the activation of lipogenesis machinery for lipid production (Fig. 1). This discovery has major implications for developing treatments for human diseases such as cancers and metabolic syndromes, as dysregulated metabolism is a hallmark of these diseases.展开更多
Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy.Increased lipid uptake,storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth.Lipids constitute the ba...Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy.Increased lipid uptake,storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth.Lipids constitute the basic struc-ture of membranes and also function as signaling molecules and energy sources.Sterol regulatory element-binding proteins(SREBPs),a family of membrane-bound transcription factors in the endoplasmic reticulum,play a central role in the regulation of lipid metabolism.Recent studies have revealed that SREBPs are highly up-regulated in various cancers and promote tumor growth.SREBP cleavage-activating protein is a key transporter in the trafficking and activation of SREBPs as well as a critical glucose sensor,thus linking glucose metabolism and de novo lipid synthesis.Targeting altered lipid metabolic pathways has become a promising anti-cancer strategy.This review summarizes recent progress in our understanding of lipid metabolism regulation in malignancy,and highlights potential molecu-lar targets and their inhibitors for cancer treatment.展开更多
To the Editor,Hepatocellular carcinoma(HCC)is a malignant tumor with the fourth highest incidence and the third highest mortality among all tumor sites in China.1 Finding new diagnostic markers and therapeutic molecul...To the Editor,Hepatocellular carcinoma(HCC)is a malignant tumor with the fourth highest incidence and the third highest mortality among all tumor sites in China.1 Finding new diagnostic markers and therapeutic molecules may be of great value in the treatment of HCC and the improvement of prognosis.展开更多
基金NIH Grant NS079701(DG)American Cancer Society Research Scholar Grant RSG-14-228-01-CSM(DG)OSUCCC Idea Grant(DG)+2 种基金OSUCCC Translational Therapeutic Program seed grant(DG)Pelotonia Postdoc Fellowship(CC)OSU Department of Radiation-Oncology Basic Research seed Grant(CC)的资助
基金supported by the National Institute of Neurological Disorders and Stroke and the National Cancer Institute grants(USA)(No.NS104332,NS112935,CA227874 and CA240726 to D.Guo)。
文摘In healthy humans, ammonia circulates in the bloodstream at a concentration around 11–32 μmol/L. Whether ammonia plays any physiological role has been unknown until a recent report published in Nature Metabolism.1 Ammonia, long thought to be a toxic waste product of amino acid metabolism, needs to be excreted from the human body as urea. Intriguingly, in this paper, Cheng et al1 for the first time reported that ammonia is not a waste product;rather, it is an unprecedented signaling molecule tying glucose and glutamine to lipid production in human cells. This study revealed that ammonia released from glutamine triggers a cascade of cellular processes leading to the activation of lipogenesis machinery for lipid production (Fig. 1). This discovery has major implications for developing treatments for human diseases such as cancers and metabolic syndromes, as dysregulated metabolism is a hallmark of these diseases.
基金supported by NIH Grant NS079701(DG)American Cancer Society Research Scholar Grant RSG-14-228-01-CSM(DG)+3 种基金OSUCCC Idea Grant(DG)an OSUCCC Translational Therapeutic Program seed grant(DG)a Pelotonia Postdoc Fellowship(CC)an OSU Department of Radiation-Oncology Basic Research seed Grant(CC).
文摘Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy.Increased lipid uptake,storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth.Lipids constitute the basic struc-ture of membranes and also function as signaling molecules and energy sources.Sterol regulatory element-binding proteins(SREBPs),a family of membrane-bound transcription factors in the endoplasmic reticulum,play a central role in the regulation of lipid metabolism.Recent studies have revealed that SREBPs are highly up-regulated in various cancers and promote tumor growth.SREBP cleavage-activating protein is a key transporter in the trafficking and activation of SREBPs as well as a critical glucose sensor,thus linking glucose metabolism and de novo lipid synthesis.Targeting altered lipid metabolic pathways has become a promising anti-cancer strategy.This review summarizes recent progress in our understanding of lipid metabolism regulation in malignancy,and highlights potential molecu-lar targets and their inhibitors for cancer treatment.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81872029 and 81772926).
文摘To the Editor,Hepatocellular carcinoma(HCC)is a malignant tumor with the fourth highest incidence and the third highest mortality among all tumor sites in China.1 Finding new diagnostic markers and therapeutic molecules may be of great value in the treatment of HCC and the improvement of prognosis.
