Hypothalamic lipid-laden astrocytes induce microglia migration and activation

FEBS Lett. 2017 Jun;591(12):1742-1751. doi: 10.1002/1873-3468.12691. Epub 2017 Jun 8.

Abstract

Obesity-induced hypothalamic inflammation is closely associated with various metabolic complications and neurodegenerative disorders. Astrocytes, the most abundant glial cells in the central nervous system, play a crucial role in pathological hypothalamic inflammatory processes. Here, we demonstrate that hypothalamic astrocytes accumulate lipid droplets under saturated fatty acid-rich conditions, such as obese environment, and that the lipid-laden astrocytes increase astrogliosis markers and inflammatory cytokines (TNFα, IL-1β, IL-6, MCP-1) at the transcript and/or protein level. Medium conditioned by the lipid-laden astrocytes stimulate microglial chemotactic activity and upregulate transcripts of the microglia activation marker Iba-1 and inflammatory cytokines. These findings indicate that the lipid-laden astrocytes formed in free fatty acid-rich obese condition may participate in obesity-induced hypothalamic inflammation through promoting microglia migration and activation.

Keywords: astrocyte; hypothalamus; inflammation; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / immunology
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Biomarkers / metabolism
  • Cell Line
  • Cell Movement
  • Cells, Cultured
  • Chemotaxis
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Fatty Acids, Nonesterified / adverse effects
  • Gene Expression Regulation*
  • Hypothalamus / cytology
  • Hypothalamus / immunology
  • Hypothalamus / metabolism*
  • Hypothalamus / pathology
  • Lipid Droplets / immunology
  • Lipid Droplets / metabolism
  • Lipid Droplets / pathology
  • Lipid Metabolism*
  • Mice, Inbred C57BL
  • Microglia / cytology
  • Microglia / immunology
  • Microglia / metabolism*
  • Microglia / pathology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Obesity / immunology
  • Obesity / metabolism
  • Obesity / pathology
  • Palmitic Acid / adverse effects
  • RNA, Messenger

Substances

  • Biomarkers
  • Cytokines
  • Fatty Acids, Nonesterified
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Palmitic Acid