Involvement of the Warburg effect in non‐tumor diseases processes

Abstract

Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid β-mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non-tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non-tumor diseases.

Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells

“…6F-H). Accumulating evidence indicated that aerobic glycolysis, also named as the Warburg effect, participates in tumor and nontumor diseases (12). Collectively, our data demonstrated that exosomes from activated HSCs induced Warburg effect of recipient KCs and LSECs.…”

“…It has been reported that aerobic glycolysis, similar to the Warburg effect described in cancer cells, is essential in reprogramming quiescent HSCs into activated HSCs (11). The Warburg effect, as a mechanism of energetic shift, is regarded as the replacement of mitochondrial oxidative phosphorylation with aerobic glycolysis of cancer cells, even in a normoxic environment (12). In the Warburg effect, glucose transporter 1 (GLUT1) acts as a rate-limiting transporter for glucose uptake and promotes diffusion and penetration of glucose and related hexoses into cells, affecting the uptake and utilization of glucose (13).…”

Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

“…The ability of pathogenic mycobacteria to subvert the host antimicrobial response may lie in its ability to interfere with the metabolic switch to aerobic glycolysis allowing mycobacterial persistence and pathogenicity [167,168]. This shift to aerobic glycolysis and its associated macrophage activation is seen in BCG's effect in T1D [169], MS [170], AD [171] and bladder cancer [172] as well as response to mycobacterial infection [173]. The "Old Friends" theory suggests that microbial exposure at a young age assists the developmental regulation of the immune system.…”

“…In the past ten years, there have been several clinical trials that re-introduce non-pathogenic BCG to stimulate immune remodeling against diverse infectious, autoimmune and allergic diseases [75,76,82,134]. Understanding that aerobic glycolysis, as stimulated by BCG, decreases amyloid-mediated neuronal death perhaps AD will soon be added to this list [154,169].…”

An improved ATP FRET sensor for yeast shows heterogeneity during nutrient transitions

“…The latter occurs in glycolysis, the central metabolic pathway in many organisms, including human. A key question is how pathway flux is regulated under dynamic conditions, which happens in nature, biotechnical processes [3][4][5][6] , but also in humans [7][8][9] . Given the task of glycolysis to produce ATP, it is not a surprise that the glycolytic flux is (also) regulated by ATP itself 10,11 .…”