Glucose metabolic crosstalk and regulation in brain function and diseases

Zhang, Shuai; Lachance, Brittany Bolduc; Mattson, Mark P.; Jia, Xiaofeng

doi:10.1016/j.pneurobio.2021.102089

Cited by 69 publications

(35 citation statements)

References 294 publications

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“…Another important function of astrocytes is to support neurons providing energy substrates and producing cholesterol. Indeed, astrocytes provide energy by storing glucose in the form of glycogen and by delivering lactate through the lactate shuttle (glucose conversion to lactate, that is then taken up by neurons) in response to glutamate released from neurons [ 33 , 34 ]. The role of astrocytes in brain cholesterol homeostasis, as well as their involvement in some pathological changes related to AD, are reported in the next Sections.…”

Section: Astrocyte Functions and Their Contribution To Alzheimer’s Diseasementioning

confidence: 99%

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

Staurenghi¹,

Giannelli²,

Testa³

et al. 2021

Antioxidants

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In recent decades, the impairment of cholesterol metabolism in the pathogenesis of Alzheimer’s disease (AD) has been intensively investigated, and it has been recognized to affect amyloid β (Aβ) production and clearance, tau phosphorylation, neuroinflammation and degeneration. In particular, the key role of cholesterol oxidation products, named oxysterols, has emerged. Brain cholesterol metabolism is independent from that of peripheral tissues and it must be preserved in order to guarantee cerebral functions. Among the cells that help maintain brain cholesterol homeostasis, astrocytes play a starring role since they deliver de novo synthesized cholesterol to neurons. In addition, other physiological roles of astrocytes are to modulate synaptic transmission and plasticity and support neurons providing energy. In the AD brain, astrocytes undergo significant morphological and functional changes that contribute to AD onset and development. However, the extent of this contribution and the role played by oxysterols are still unclear. Here we review the current understanding of the physiological role exerted by astrocytes in the brain and their contribution to AD pathogenesis. In particular, we focus on the impact of cholesterol dysmetabolism on astrocyte functions suggesting new potential approaches to develop therapeutic strategies aimed at counteracting AD development.

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Section: Astrocyte Functions and Their Contribution To Alzheimer’s Diseasementioning

confidence: 99%

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

Staurenghi¹,

Giannelli²,

Testa³

et al. 2021

Antioxidants

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“…Of special interest may be a lack of significant changes in the levels of G6PD, which is a key regulatory enzyme in the pentose phosphate pathway (PPP). G6PD expression and activity are critical for maintaining the proper redox cellular status [46], and its retained activity in the WD group may be-hypothetically-a protective mechanism. Previously, a significant decrease in the mRNA expression of HK1, glucokinase, and pyruvate kinase was observed in the livers of mice fed with a high-fat diet (HFD) [47].…”

Section: Discussionmentioning

confidence: 99%

Effects of Simultaneous Exposure to a Western Diet and Wheel-Running Training on Brain Energy Metabolism in Female Rats

Nowacka-Chmielewska¹,

Liśkiewicz²,

Grabowska

et al. 2021

Nutrients

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Background: In the pathogenesis of central nervous system disorders (e.g., neurodegenerative), an important role is attributed to an unhealthy lifestyle affecting brain energy metabolism. Physical activity in the prevention and treatment of lifestyle-related diseases is getting increasing attention. Methods: We performed a series of assessments in adult female Long Evans rats subjected to 6 weeks of Western diet feeding and wheel-running training. A control group of lean rats was fed with a standard diet. In all experimental groups, we measured physiological parameters (animal weights, body composition, serum metabolic parameters). We assessed the impact of simultaneous exposure to a Western diet and wheel-running on the cerebrocortical protein expression (global proteomic profiling), and in the second part of the experiment, we measured the cortical levels of protein related to brain metabolism (Western blot). Results: Western diet led to an obese phenotype and induced changes in the serum metabolic parameters. Wheel-running did not reduce animal weights or fat mass but significantly decreased serum glucose level. The global proteome analysis revealed that the altered proteins were functionally annotated as they were involved mostly in metabolic pathways. Western blot analysis showed the downregulation of the mitochondrial protein—Acyl-CoA dehydrogenase family member 9, hexokinase 1 (HK1)—enzyme involved in principal glucose metabolism pathways and monocarboxylate transporter 2 (MCT2). Wheel-running reversed this decline in the cortical levels of HK1 and MCT2. Conclusion: The cerebrocortical proteome is affected by a combination of physical activity and Western diet in female rats. An analysis of the cortical proteins involved in brain energy metabolism provides a valuable basis for the deeper investigation of changes in the brain structure and function induced by simultaneous exposure to a Western diet and physical activity.

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“…AMPK is one of the main regulators of cell energy status and key cellular processes such as lipid and glucose metabolism, cell growth, autophagy and apoptosis. This enzyme maintains mitochondrial homeostasis and is activated when the ratio of AMP or ADP to ATP increases, and compensates for energy loss by upregulating glycolysis ( 80 ). Tumors such as breast ( 81 ), pancreatic ( 82 ) and prostate cancer ( 83 ) are related to obesity, which in turn is associated with the AMPK/mTOR metabolic pathway ( 84 ).…”

Section: Metformin As An Antitumor Candidate Drugmentioning

confidence: 99%

Metformin: A promising drug for human cancers (Review)

Huang

Zhao

et al. 2022

Oncol Lett

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Small-molecule chemical drugs are of great significance for tumor-targeted and individualized therapies. However, the development of new small-molecule drugs, from basic experimental research and clinical trials to final application in clinical practice, is a long process that has a high cost. It takes at least 5 years for most drugs to be developed in the laboratory to prove their effectiveness and safety. Compared with the development of new drugs, repurposing traditional non-tumor drugs can be a shortcut. Metformin is a good model for a new use of an old drug. In recent years, the antitumor efficacy of metformin has attracted much attention. Epidemiological data and in vivo , and in vitro experiments have shown that metformin can reduce the incidence of cancer in patients with diabetes and has a strong antagonistic effect on metabolism-related tumors. Recent studies have shown that metformin can induce autophagy in esophageal cancer cells, mainly by inhibiting inflammatory signaling pathways. In recent years, studies have shown that the antitumor functions and mechanisms of metformin are multifaceted. The present study aims to review the application of metformin in tumor prevention and treatment.

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Glucose metabolic crosstalk and regulation in brain function and diseases

Cited by 69 publications

References 294 publications

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

Effects of Simultaneous Exposure to a Western Diet and Wheel-Running Training on Brain Energy Metabolism in Female Rats

Metformin: A promising drug for human cancers (Review)

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