Profiling and Cellular Analyses of Obesity-Related circRNAs in Neurons and Glia under Obesity-like In Vitro Conditions

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6235
• Main Authors: Jo, Danbi, Yoon, Gwangho, Lim, Yeonghwan, Kim, Youngkook, Song, Juhyun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.03.2023; MDPI
• Subjects: Alzheimer's disease; Animals; Apoptosis; Astrocytes; Astrocytes - metabolism; Autophagy; Brain; Cell cycle; Cholesterol; circular RNAs (circRNAs); Cytokines; Development and progression; Diabetes; Diabetes mellitus; Fatty acids; Genes; Glucose; Homeostasis; Humans; Inflammation; Insulin resistance; Interleukin 6; Linoleic acid; Memory; Metabolic disorders; Metabolism; Mice; Microglia; MicroRNAs; Nervous system diseases; Neurodegenerative Diseases - genetics; Neuronal-glial interactions; Neurons; Neurons - metabolism; Obesity; Obesity - genetics; Oxidation; Palmitic acid; Pathogenesis; RNA, Circular - genetics; RNA, Circular - metabolism; Roles; Saturated fatty acids; Scavenger receptors; Scientific equipment and supplies industry; siRNA; Synaptic density; Synaptic vesicles; Tumor necrosis factor-TNF; Type 2 diabetes; Unsaturated fatty acids; United States; South Korea; Massachusetts; astrocytes; microglia; neurons; circular RNAs (circRNAs); obesity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076235

Recent evidence indicates that the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, is associated with metabolic disorders such as diabetes and obesity. Various circular RNAs (circRNAs) have been found in brain tissues and recent studies have suggested that circRNAs are related to neuropathological mechanisms in the brain. However, there is a lack of interest in the involvement of circRNAs in metabolic imbalance-related neuropathological problems until now. Herein we profiled and analyzed diverse circRNAs in mouse brain cell lines (Neuro-2A neurons, BV-2 microglia, and C8-D1a astrocytes) exposed to obesity-related in vitro conditions (high glucose, high insulin, and high levels of tumor necrosis factor-alpha, interleukin 6, palmitic acid, linoleic acid, and cholesterol). We observed that various circRNAs were differentially expressed according to cell types with many of these circRNAs conserved in humans. After suppressing the expression of these circRNAs using siRNAs, we observed that these circRNAs regulate genes related to inflammatory responses, formation of synaptic vesicles, synaptic density, and fatty acid oxidation in neurons; scavenger receptors in microglia; and fatty acid signaling, inflammatory signaling cyto that may play important roles in metabolic disorders associated with neurodegenerative diseases.