Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss

Sci Rep. 2019 Nov 6;9(1):16161. doi: 10.1038/s41598-019-52257-8.


The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity
  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Astrocytes / metabolism
  • Biomarkers
  • Diet, High-Fat
  • Diet, Reducing*
  • Eating
  • Gastric Bypass*
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Glial Fibrillary Acidic Protein / analysis
  • Gliosis / genetics*
  • Glucagon-Like Peptide 1 / blood
  • Inflammation / genetics
  • Laser Capture Microdissection
  • Male
  • Neuropeptides / biosynthesis
  • Neuropeptides / genetics
  • Obesity / etiology
  • Obesity / surgery
  • Peptide YY / blood
  • Rats
  • Rats, Sprague-Dawley
  • Sequence Analysis, RNA
  • Weight Loss


  • Biomarkers
  • GFAP protein, rat
  • Glial Fibrillary Acidic Protein
  • Neuropeptides
  • Peptide YY
  • Glucagon-Like Peptide 1