Characterization of apolipoprotein A-IV in brain areas involved in energy homeostasis.
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, (125)I-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 (99m)Tc-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.
Shen
Ling
L
Obesity Research Center, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
Pearson
Kevin J
KJ
Xiong
Ye
Y
Lo
Chun-Min
CM
Tso
Patrick
P
Woods
Stephen C
SC
Davidson
W Sean
WS
Liu
Min
M
D000818:Animals; D001054:Apolipoproteins A / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D005215:Fasting / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007456:Iodine Isotopes / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D013668:Technetium Tc 99m Aggregated Albumin / Q000378:metabolism; D013997:Time Factors
D001054:Apolipoproteins A; D005904:Glial Fibrillary Acidic Protein; D007456:Iodine Isotopes; D013668:Technetium Tc 99m Aggregated Albumin; C022205:apolipoprotein A-IV; D011333:Pro-Opiomelanocortin; D010751:Phosphopyruvate Hydratase