Characterization of apolipoprotein A-IV in brain areas involved in energy homeostasis

Ling Shen, Kevin J. Pearson, Ye Xiong, Chun Min Lo, Patrick Tso, Stephen C. Woods, W. Sean Davidson, Min Liu

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Apolipoprotein A-IV (apo A-IV) is a satiation protein synthesized in the small intestine and hypothalamus. To further understand its anorectic mechanisms, we used immunohistochemical techniques to characterize the distribution of apo A-IV in brain areas involved in energy homeostasis. Dense apo A-IV staining was detected in the arcuate (ARC) and ventromedial hypothalamic nuclei with less staining in cells in the paraventricular and dorsomedial nuclei. In the brainstem, apo A-IV staining was found in the nucleus of the solitary tract. Double-staining immunohistochemistry revealed co-existence of apo A-IV with neuronal nuclei (a neuronal marker), but less with glial fibrillary acidic protein (a glial marker), in ARC, suggesting that apo A-IV is largely present in neurons. In the ARC, apo A-IV was co-localized with pro-opiomelanocortin (POMC), and apo A-IV administration stimulated hypothalamic POMC gene expression, suggesting that the brain apo A-IV system suppresses food intake by stimulating the ARC POMC system. To ascertain whether the apo A-IV detected in the brain is derived from the circulation, 125I-labeled recombinant rat apo A-IV was intravenously injected into mice. No increase of radioactive apo A-IV was found in the brain, consistent with a lack of uptake of co-injected 99mTc-labeled albumin, indicating that circulating apo A-IV is unable to cross the blood brain barrier. These data collectively support the hypothesis that apo A-IV, produced by neuronal cells, may exert its anorectic action by interacting with catabolic regulatory neuropeptides.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalPhysiology and Behavior
Issue number1-2
StatePublished - Sep 3 2008


  • Apolipoproteins
  • Blood brain barrier
  • Immunohistochemistry
  • Neuropeptides

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience


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