Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake

Kishor Bugarith; Thu T Dinh; Ai-Jun Li; Robert C Speth; Sue Ritter

doi:10.1210/en.2004-1166

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Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake

Journal article

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Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake

Kishor Bugarith, Thu T Dinh, Ai-Jun Li, Robert C Speth and Sue Ritter

Endocrinology (Philadelphia), Vol.146(3), pp.1179-1191

03/2005

DOI: https://doi.org/10.1210/en.2004-1166

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https://hdl.handle.net/2376/116042

PMID: 15604214

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Abstract

Immunohistochemistry

Glucagon-Like Peptide 1

Body Weight

Catecholamines - metabolism

Leptin - metabolism

Male

RNA, Messenger - metabolism

alpha-MSH - metabolism

Neuropeptide Y - metabolism

Peptide Hormones - metabolism

Cholecystokinin - metabolism

In Situ Hybridization

Time Factors

Ghrelin

Arcuate Nucleus of Hypothalamus - drug effects

Inhibitory Concentration 50

Neurons - metabolism

Hypothalamus - drug effects

Binding, Competitive

Peptide Fragments - metabolism

Plant Proteins - pharmacology

Dopamine Uptake Inhibitors - pharmacology

Peptides - chemistry

Intercellular Signaling Peptides and Proteins

Rats

Neuropeptide Y - pharmacology

Thioglycolates - metabolism

Rats, Sprague-Dawley

Protein Precursors - metabolism

Pro-Opiomelanocortin - metabolism

Cocaine - pharmacology

Animals

Proteins - metabolism

Amphetamines - metabolism

Models, Biological

Protein Binding

Rhombencephalon - metabolism

Glucagon - metabolism

Ligands

Toxins, Biological - chemistry

Agouti-Related Protein

Neuropeptide Y (NPY) conjugated to saporin (NPY-SAP), a ribosomal inactivating toxin, is a newly developed compound designed to selectively target and lesion NPY receptor-expressing cells. We injected NPY-SAP into the basomedial hypothalamus (BMH), just dorsal to the arcuate nucleus (ARC), to investigate its neurotoxicity and to determine whether ARC NPY neurons are required for glucoprivic feeding. We found that NPY-SAP profoundly reduced NPY Y1 receptor and alpha MSH immunoreactivity, as well as NPY, Agouti gene-related protein (AGRP), and cocaine and amphetamine-related transcript mRNA expression in the BMH. NPY-SAP lesions were localized to the injection site with no evidence of retrograde transport by hindbrain NPY neurons with BMH terminals. These lesions impaired responses to intracerebroventricular (icv) leptin (5 microg/5 microl x d) and ghrelin (2 microg/5 microl), which are thought to alter feeding primarily by actions on ARC NPY/AGRP and proopiomelanocortin/cocaine and amphetamine-related transcript neurons. However, the hypothesis that NPY/AGRP neurons are required downstream mediators of glucoprivic feeding was not supported. Although NPY/AGRP neurons were destroyed by NPY-SAP, the lesion did not impair either the feeding or the hyperglycemic response to 2-deoxy-D-glucose-induced blockade of glycolysis use. Similarly, responses to glucagon-like peptide-1 (GLP-1, 5 microg/3 microl icv), NPY (5 microg/3 microl icv), cholecystokinin octapeptide (4 microg/kg ip), and beta-mercaptoacetate (68 mg/kg ip) were not altered by the NPY-SAP lesion. Thus, NPY-SAP destroyed NPY receptor-expressing neurons in the ARC and selectively disrupted controls of feeding dependent on those neurons but did not disrupt peptidergic or metabolic controls dependent upon circuitry outside the BMH.

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Title: Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake
Creators: Kishor Bugarith - Programs in Neuroscience, Washington State University, Pullman, Washington 99164-6520, USA
Thu T Dinh
Ai-Jun Li
Robert C Speth
Sue Ritter
Publication Details: Endocrinology (Philadelphia), Vol.146(3), pp.1179-1191
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: United States
Grant note: DK 40498 / NIDDK NIH HHS NS045520 / NINDS NIH HHS
Identifiers: 99900547432001842
Language: English
Resource Type: Journal article