Dataset Information

Hypothalamus proteomics from mouse models with obesity and anorexia reveals novel therapeutic targets of appetite regulation

ABSTRACT: This study examined the proteomic profile of hypothalamus in mouse models of obesity and anorexia

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Spiro Garbis

LAB HEAD: Spiros D. Garbis

PROVIDER: PXD003475 | Pride | 2016-03-11

REPOSITORIES: Pride

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			Action	DRS
	13OCT14_KK_HYPOTHALAMUS_19.raw	Raw
	13OCT14_KK_HYPOTHALAMUS_20.raw	Raw
	13OCT14_KK_HYPOTHALAMUS_21.raw	Raw
	13OCT14_KK_HYPOTHALAMUS_22.raw	Raw
	13OCT14_KK_HYPOTHALAMUS_23.raw	Raw

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Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation.

Manousopoulou A A Koutmani Y Y Karaliota S S Woelk C H CH Manolakos E S ES Karalis K K Garbis S D SD

Nutrition & diabetes 20160425

<h4>Objective</h4>This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation.<h4>Methods</h4>Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal ...[more]

PMID: 27110685

Similar Datasets

Project description:ObjectiveThis study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation.MethodsFour to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR.ResultsQuantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased.ConclusionsHigh-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms mediating a sustained 'perpetual cycle' of appetite enhancement were observed. The GlyR protein may constitute a novel treatment target for the reduction of central orexigenic signals in obesity.