Unknown,Transcriptomics,Genomics,Proteomics

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Expression of obese mice subjected to diet induced weight loss for 60 days

ABSTRACT: We used microarrays to study the gene expression dynamics during caloric restricted weight loss in obese mice after feeded with high fat diet. C57BL/6J male mice were placed on a high fat diet at 10-11 weeks of age in individual cages and kept on the diet until they reached ~ 41 g. After all the baseline (41g) measurement were made, each mouse was fed 75% of their ad libitum food intake in two divided daily "meals". The high fat diet was maintained. Mice were sacrificed after 0, 1, 3, 7, 14, 21 or 42 day of caloric restriction. Hypothalamus, liver, abdominal subcutaneous adipose, mesenteric adipose, perirenal adipose and perigonadal adipose tissues were collected for RNA extraction and hybridization on Affymetrix microarrays.

ORGANISM(S): Mus musculus

SUBMITTER: Zhi Wang

PROVIDER: E-GEOD-30534 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation. Three mouse strains (C57BL6 on chow diet, C57BL6 on high fat diet, and db/db on chow diet) were treated with either vehicle, wild-type FGF21, or pegylated FGF21 acutely or for several days and three white adipose tissues (IWAT, EWAT, RPWAT) and brown adipose tissue (BAT) were profiled on custom Affymetrix microarrays. The primary goal was to identify robust and consistent acute target engagement biomarkers of FGF21 activation in white adipose tissues.

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Expression of obese mice subjected to diet induced weight loss for 60 days

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