Leptin receptor long-form splice-variant protein expression in neuron cell bodies of the brain and co-localization with neuropeptide Y mRNA in the arcuate nucleus
- PMID: 10026237
- DOI: 10.1177/002215549904700309
Leptin receptor long-form splice-variant protein expression in neuron cell bodies of the brain and co-localization with neuropeptide Y mRNA in the arcuate nucleus
Abstract
Reduced leptin (Ob protein) signaling is proposed to be a stimulus for the activation of neuropeptide Y (NPY) gene activity and increased expression of mRNA for the long form of the leptin receptor (Ob-Rb) in the hypothalamic arcuate nucleus. To determine if Ob-Rb protein is expressed in arcuate nucleus NPY neurons, we developed an affinity-purified polyclonal antibody against amino acids 956-1102 of human Ob-Rb. This antibody specifically recognizes the cytoplasmic tail of Ob-Rb and does not react with shorter leptin-receptor variants. Western immunoblots of Ob-Rb-transfected COS cells showed a single 150-kD band, and immunofluorescence revealed intense perinuclear staining in the cytoplasm. A 150-kD band was also present in Western immunoblots of hypothalamus. Immunocytochemical staining of brain slices revealed immunoreactive Ob-Rb protein concentrated in many neuronal cell bodies in the same regions of the forebrain that also express Ob-Rb mRNA. In the hypothalamus, Ob-Rb-positive cell bodies were abundant in the arcuate nucleus and ventromedial nucleus, with lesser numbers in the dorsomedial nucleus and paraventricular nucleus. Immunostaining was also detected in cell bodies of pyramidal cell neurons of the pyriform cortex and cerebral cortex, in neurons of the thalamus, and on the surface of ependymal cells lining the third ventricle. The choroid plexus, which expresses the short Ob-Ra form, was negative. Combined immunocytochemistry for Ob-Rb protein and fluorescence in situ hybridization for NPY mRNA identified arcuate nucleus neurons containing both NPY mRNA and Ob-Rb protein. The present finding of Ob-Rb protein in neurons that express NPY mRNA supports the hypothesis that arcuate nucleus NPY neurons are direct targets of leptin and play an important role in regulation of food intake and body weight.
Similar articles
-
Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus.Diabetes. 1999 Apr;48(4):828-33. doi: 10.2337/diabetes.48.4.828. Diabetes. 1999. PMID: 10102700
-
Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting.Diabetes. 1998 Apr;47(4):538-43. doi: 10.2337/diabetes.47.4.538. Diabetes. 1998. PMID: 9568684
-
Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus.J Neuroendocrinol. 1996 Oct;8(10):733-5. doi: 10.1046/j.1365-2826.1996.05161.x. J Neuroendocrinol. 1996. PMID: 8910801
-
Control of food intake via leptin receptors in the hypothalamus.Vitam Horm. 2000;59:265-304. doi: 10.1016/s0083-6729(00)59010-4. Vitam Horm. 2000. PMID: 10714243 Review.
-
A role for dietary fat in leptin receptor, OB-Rb, function.Life Sci. 2001 Jul 20;69(9):987-1003. doi: 10.1016/s0024-3205(01)01201-2. Life Sci. 2001. PMID: 11508653 Review.
Cited by
-
Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia.Nutrients. 2022 Nov 13;14(22):4803. doi: 10.3390/nu14224803. Nutrients. 2022. PMID: 36432490 Free PMC article.
-
Decreased excitability of leptin-sensitive anterior insula pyramidal neurons in a rat model of compulsive food demand.Neuropharmacology. 2022 May 1;208:108980. doi: 10.1016/j.neuropharm.2022.108980. Epub 2022 Feb 2. Neuropharmacology. 2022. PMID: 35122838 Free PMC article.
-
A Tale of Three Systems: Toward a Neuroimmunoendocrine Model of Obesity.Annu Rev Cell Dev Biol. 2021 Oct 6;37:549-573. doi: 10.1146/annurev-cellbio-120319-114106. Annu Rev Cell Dev Biol. 2021. PMID: 34613819 Free PMC article. Review.
-
Leptin-a mediates transcription of genes that participate in central endocrine and phosphatidylinositol signaling pathways in 72-hour embryonic zebrafish (Danio rerio).PeerJ. 2019 May 3;7:e6848. doi: 10.7717/peerj.6848. eCollection 2019. PeerJ. 2019. PMID: 31110923 Free PMC article.
-
Leptin - a slimmer's dream that crashed?EJIFCC. 2000 Sep 1;12(3):73-81. eCollection 2000 Sep. EJIFCC. 2000. PMID: 30532682 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous