Adiponectin Controls Nutrient Availability in Hypothalamic Astrocytes

Song, Nuri; Jeong, Da Yeon; Tu, Thai Hien; Park, Byong Seo; Yang, Hye Rim; Kim, Ye Jin; Kim, Jae Kwang; Park, Taezoon; Yeh, Jung‐Yong; Yang, Sunggu

doi:10.3390/ijms22041587

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…It should be mentioned here that there is inconsistent data regarding HMGCS2 expression in the nervous tissue. While some authors showed a lack of expression of HMGCS2 in astrocytes and neurons ( Thevenet et al, 2016 ), the latest studies confirm the astrocytic expression of HMGCS mRNA ( Song et al, 2021 ). HMGCS has been found to be abundantly expressed in the astrocytes of the optic nerve ( Metwally et al, 2019 ) and other glial cells ( Wang et al, 2016 ) and various brain areas ( Shao et al, 2019 ; Kondo et al, 2020 ), including the hippocampus ( Wang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet

Liśkiewicz

Nowacka-Chmielewska

et al. 2021

Front. Cell. Neurosci.

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Experimental and clinical data support the neuroprotective properties of the ketogenic diet and ketone bodies, but there is still a lot to discover to comprehensively understand the underlying mechanisms. Autophagy is a key mechanism for maintaining cell homeostasis, and therefore its proper function is necessary for preventing accelerated brain aging and neurodegeneration. Due to many potential interconnections, it is possible that the stimulation of autophagy may be one of the mediators of the neuroprotection afforded by the ketogenic diet. Recent studies point to possible interconnections between ketone body metabolism and autophagy. It has been shown that autophagy is essential for hepatic and renal ketogenesis in starvation. On the other hand, exogenous ketone bodies modulate autophagy both in vitro and in vivo. Many regional differences occur between brain structures which concern i.e., metabolic responses and autophagy dynamics. The aim of the present study was to evaluate the influence of the ketogenic diet on autophagic markers and the ketone body utilizing and transporting proteins in the hippocampus and frontal cortex. C57BL/6N male mice were fed with two ketogenic chows composed of fat of either animal or plant origins for 4 weeks. Markers of autophagosome formation as well as proteins associated with ketolysis (BDH1—3-hydroxybutyrate dehydrogenase 1, SCOT/OXCT1—succinyl CoA:3-oxoacid CoA transferase), ketone transport (MCT1—monocarboxylate transporter 1) and ketogenesis (HMGCL, HMGCS2) were measured. The hippocampus showed a robust response to nutritional ketosis in both changes in the markers of autophagy as well as the levels of ketone body utilizing and transporting proteins, which was also accompanied by increased concentrations of ketone bodies in this brain structure, while subtle changes were observed in the frontal cortex. The magnitude of the effects was dependent on the type of ketogenic diet used, suggesting that plant fats may exert a more profound effect on the orchestrated upregulation of autophagy and ketone body metabolism markers. The study provides a foundation for a deeper understanding of the possible interconnections between autophagy and the neuroprotective efficacy of nutritional ketosis.

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Section: Discussionmentioning

confidence: 99%

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet

Liśkiewicz

Nowacka-Chmielewska

et al. 2021

Front. Cell. Neurosci.

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“…Changes in the physical transportation and biochemical processes of fuel sources in the vessel–astrocyte-neurons axis of the hypothalamus are important in the hypothalamic circuit regulating whole-body energy metabolism. Considerable effort has been made to unveil the functional role of hypothalamic astrocytes in the hypothalamic control of energy metabolism [ 6 , 7 , 10 , 11 , 23 , 24 ]. For instance, the modification of glucose and fatty acid availability in hypothalamic astrocytes altered the susceptibility to obesity development in association with altered activities of hunger- and satiety-regulating neurons in the hypothalamic arcuate nucleus [ 6 , 7 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Profiling of the Hypothalamus of Mice during Short-Term Food Deprivation

et al. 2022

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Nutrient availability and utilization in hypothalamic cells are directly associated with the regulation of whole-body energy homeostasis. Thus, establishing metabolic profiling in the hypothalamus in response to metabolic shift is valuable to better understand the underlying mechanism of appetite regulation. In the present study, we evaluate the alteration of lipophilic and hydrophilic metabolites in both the hypothalamus and serum of fasted mice. Fasted mice displayed an elevated ketone body and decreased lactate levels in the hypothalamus. In support of the metabolite data, we further confirmed that short-term food deprivation resulted in the altered expression of genes involved in cellular metabolic processes, including the shuttling of fuel sources and the production of monocarboxylates in hypothalamic astrocytes. Overall, the current study provides useful information to close the gap in our understanding of the molecular and cellular mechanisms underlying hypothalamic control of whole-body energy metabolism.

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“…The sample was transferred into auto-sampler vials and analyzed by gas chromatography-mass spectrometry (GC-MS, a GCMS-QP2010 Ultra system, Shimadzu, Kyoto, Japan). GC-MS analysis was performed as previously described (Song et al 2021 ). Pearson's correlation analysis was carried out using SAS software 9.4 (SAS Institute, San Diego, CA, USA) and then visualized with Hierarchical Clustering Analysis (HCA) using Multi-Experiment Viewer version 4.9.0 (MeV; https://webmev.tm4.org ).…”

Section: Methodsmentioning

confidence: 99%

Metabolic reprogramming as a novel therapeutic target for Coxsackievirus B3

Kuk

Kim

et al. 2022

Animal Cells and Systems

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Coxsackievirus B3 (CVB3) is a single-stranded RNA virus that belongs to the Enterovirus genus. CVB3 is a human pathogen associated with serious conditions such as myocarditis, dilated cardiomyopathy, and pancreatitis. However, there are no therapeutic interventions to treat CVB3 infections. In this study, we found that CVB3 induced metabolic alteration in host cells through increasing glycolysis level, as indicated by an increase in the extracellular acidification rate (ECAR). CVB3-mediated metabolic alteration was confirmed by metabolite change analysis using gas chromatography-mass spectrometry (GC-MS). Based on findings, a strategy to inhibit glycolysis has been proposed to treat CVB3 infection. Indeed, glycolysis inhibitors (2-Deoxy-D-glucose, sodium oxide) significantly reduced CVB3 titers after CVB3 infection, indicating that glycolysis inhibitors can be used as effective antiviral agents. Taken together, our results reveal a novel mechanism by which CVB3 infection is controlled by regulation of host cell metabolism.

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Adiponectin Controls Nutrient Availability in Hypothalamic Astrocytes

Cited by 12 publications

References 29 publications

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet

Metabolic Profiling of the Hypothalamus of Mice during Short-Term Food Deprivation

Metabolic reprogramming as a novel therapeutic target for Coxsackievirus B3

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