Apolipoprotein A-IV Inhibits AgRP/NPY Neurons and Activates Pro-Opiomelanocortin Neurons in the Arcuate Nucleus

Neuroendocrinology
Chunling YanYong Xu

Abstract

Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However, the mechanisms underlying its anorexigenic effects remain to be identified. We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) and in neurons that express pro-opiomelanocortin (POMC). We then compared anorexigenic effects of apoA-IV in wild-type mice and in mutant mice lacking melanocortin 4 receptors (MC4Rs; the receptors of AgRP and the POMC gene product). Finally, we examined expression of apoA-IV in mouse hypothalamus and quantified its protein levels at fed versus fasted states. We demonstrate that apoA-IV inhibited the firing rate of AgRP/NPY neurons. The decreased firing was associated with hyperpolarized membrane potential and decreased miniature excitatory postsynaptic current. We further used c-fos immunoreactivity to show that intracerebroventricular (i.c.v.) injections of apoA-IV abolished the fasting-induced activation of AgRP/NPY neurons in mice. Further, we found that apoA-IV depolarized POMC neurons and increased their firing rate. In addition, genetic deletion of MC4Rs blocked anorexigenic effects of i.c.v. apoA-IV. Final...Continue Reading

Citations

Nov 7, 2017·Nature Medicine·Clemens DuerrschmidAtul R Chopra
Mar 2, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Minsoo KangJesang Ko
Aug 23, 2016·Nature Neuroscience·Xiaobing Zhang, Anthony N van den Pol
Jun 18, 2019·SAGE Open Medicine·Eivind LarssenMari Mæland Nilsen
Jul 3, 2019·International Journal of Molecular Sciences·Sydney PenceChunmin C Lo
Jan 31, 2021·International Journal of Molecular Sciences·Sydney PenceChunmin C Lo

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