The Contribution of Astrocyte Autophagy to Systemic Metabolism

Abstract

Autophagy is an essential mechanism to maintain cellular homeostasis. Besides its role in controlling the quality of cytoplasmic components, it participates in nutrient obtaining and lipid mobilization under stressful conditions. Furthermore, autophagy is involved in the regulation of systemic metabolism as its blockade in hypothalamic neurons can affect the central regulation of metabolism and impact body energy balance. Moreover, hypothalamic autophagy can be altered during obesity, one of the main alterations of metabolism nowadays. In this review, we focus on the role of astrocytes, essential cells for brain homeostasis, which represent key metabolic regulators. Astrocytes can sense metabolic signals in the hypothalamus and modulate systemic functions as glucose homeostasis and feeding response. Moreover, the response of astrocytes to obesity has been widely studied. Astrocytes are important mediators of brain inflammation and can be affected by increased levels of saturated fatty acids associated with obesity. Although autophagy plays important roles for astrocyte homeostasis and functioning, the contribution of astrocyte autophagy to systemic metabolism has not been analyzed yet. Furthermore, how obesity can impact astrocyte autophagy is poorly understood. More studies are needed in order to understand the contribution of astrocyte autophagy to metabolism.

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

“…But under standard conditions most neuronal ACSS2 is already localized to the nucleus. Since PDK2 and NF-κB play pro-inflammatory and pro-aging roles in glial cells, the AMPK-ACSS2-TFEB pathway likely stimulates autophagy in hypothalamic astrocytes to decrease inflammation and slow the rate of aging [ 448 ]. Further research is needed (1) to elucidate the mechanisms through which ACSS2 mediates these opposing effects on autophagy in different tissues, (2) to decipher the mechanisms through which HDAC inhibitors delay aging, (3) to determine the mechanisms through which CR increases CBP expression in the hypothalamus, (4) to determine if hypothalamic CBP-mediated histone acetylation promotes longevity in mammals by inducing the UPR mt , and (5) to determine if GTA or other acetate-releasing compounds that increase brain histone acetylation can mimic the anti-aging effects of HDAC inhibitors and CR.…”

Deficiency in Androgen Receptor Aggravates Traumatic Brain Injury-Induced Pathophysiology and Motor Deficits in Mice

“…In hypoxia-ischemia-induced brain injury, Beclin-1 has been observed to colocalize with neurons but not GFAP-positive cells [90]. A recent study has also reported that hypothalamic astrocyte autophagy regulates obesity and systemic metabolism [91]. The antidepressant fluoxetine has also been suggested to promote autophagic flux and enhance autophagosome fusion in astrocytes [92].…”

Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Current Evidence and Future Perspectives

“…Glial fibrillary acidic protein (GFAP), with molecular weight 50 kDa, encoded by the human GFAP gene found on chromosome 17q21, is a class-III intermediate filament that is expressed by astrocytes in the central nervous system [ 227 , 228 ]. GFAP is an astrocyte-specific biomarker that has a role in cell mobility and migration, proliferation and astrocyte transformation, vesicle transport and autophagy, and astrocyte–neuron interactions [ 229 , 230 ].…”