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Hepatic gene expression in wild type and SHPKO mice fed chow or western diet

ABSTRACT: SHP (small heterodimer partner; NR0B2) belongs to the nuclear hormone receptor superfamily, which regulates numerous developmental and metabolic cellular functions. To study physiological function of SHP, we generated congenic SHP-/- mice on C57Bl/6 background. When the congenic SHP-/- mice were challenged with a western diet (harlan, TD.88137) for 22 weeks, they were resistant to diet induced obesity and hepatic steatosis compared to WT controls. However, their hepatic insulin sensitivity was compromised when assessed with phospho-Akt levels after insulin injection. Therefore, we investigated hepatic gene expression using illumina beadchip array to explore mechanisms underneath the unique liver physiology in SHP-/- mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE38013 | GEO | 2012/05/17

SECONDARY ACCESSION(S): PRJNA167094

REPOSITORIES: GEO

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Hepatic gene expression in wild type and SHPKO mice fed chow or western diet

Project description:SHP (small heterodimer partner; NR0B2) belongs to the nuclear hormone receptor superfamily, which regulates numerous developmental and metabolic cellular functions. To study physiological function of SHP, we generated congenic SHP-/- mice on C57Bl/6 background. When the congenic SHP-/- mice were challenged with a western diet (harlan, TD.88137) for 22 weeks, they were resistant to diet induced obesity and hepatic steatosis compared to WT controls. However, their hepatic insulin sensitivity was compromised when assessed with phospho-Akt levels after insulin injection. Therefore, we investigated hepatic gene expression using illumina beadchip array to explore mechanisms underneath the unique liver physiology in SHP-/- mice. Livers were collected from C57Bl/6 wild type and C57Bl/6 SHP-/- mice fed chow or western diet. The 1 microgram of total RNA obtained from individual mouse (n=4 per group) and subjected to illumina beadchip gene expression profiling.

2012-05-16 | E-GEOD-38013 | biostudies-arrayexpress

mRNA expression in islets isolated from wild type and SHPKO mice fed chow or western diet

Project description:SHP (small heterodimer partner; NR0B2) belongs to the nuclear hormone receptor superfamily, which regulates numerous developmental and metabolic cellular functions. To study physiological function of SHP, we generated congenic SHP-/- mice on C57Bl/6 background. When the congenic SHP-/- mice were challenged with a western diet (high fat, hgih sucrose, high cholesterol) for 20 weeks, they were resistant to diet induced obesity but severely glucose intolerant compared to wild type control mice. However, their overall peripheral tissue insulin sensitivity was normal when assessed by insulin tolerance test. Next, we examined the glucose stimulated insulin secretion (GSIS) in isolated islets from these animals. Islets from SHP-/- mice showed strongly impaired GSIS especially fed the western diet, which is believed to be a major factor causing the whole body glucose intolerance in SHP-/- mice. Therefore, we explored gene expression in islets using illumina beadchip array to understand mechanisms underneath the impaired GSIS.

2010-02-24 | GSE20518 | GEO

Liver gene expression profile _ wild type_ CYP7A1 transgenic

Project description:Bile acids are not only physiological detergents facilitating nutrient absorption, but also signaling molecules regulating metabolic homeostasis. We reported recently that transgenic expression of CYP7A1 in mice stimulated bile acid synthesis and prevented Western diet-induced obesity, insulin resistance and hepatic steatosis. The aim of this experiment is to determine the impact of induction of hepatic bile acid synthesis on liver metabolism by determining hepatic gene expression profile in CYP7A1 transgenic mice. CYP7A1 transgenic mice and wild type control mice were fed either standard chow diet or high fat high cholesterol Western diet for 4 month. Hepatic gene expressions were measured by microarray analysis. Our results indicate that hepatic bile acid synthesis is closely linked to cholesterogenesis and lipogenesis, and maintaining bile acid homeostasis is improtant in hepatic metabolic homeostasis. Male aged matched (~ 12-14 weeks) CYP7A1 transgenic mice and their wild type control littermates were fed a standard chow diet or a high fat (42%) high cholesterol (0.2%) diet (Harlan Teklad #88137) for 4 month Four groups (4 mice/group) are included in the experiments: Group 1: WT _ Chow Group 2: CYP7A1-tg + chow Group 3: WT + Western diet Group 4: CYP7A1-tg _ Western diet Total liver mRNA was isolated with a RNeasy kit (Qiagen) and used for microarray analysis.

2013-08-15 | E-GEOD-38872 | biostudies-arrayexpress

Aortic arch profiling of Apoe knockout mice

2010-06-23 | GSE18443 | GEO

Intestinal FGF15/19 physiologically represses hepatic lipogenesis in the late fed-state by activating SHP and DNMT3A

Project description:Hepatic lipogenesis is normally tightly regulated but is aberrantly elevated in obesity. Fibroblast Growth Factor-19 (FGF19, mouse FGF15) is a late fed-state gut hormone that decreases hepatic lipid levels by unclear mechanisms. We examined whether FGF15/19 and FGF15/19-activated Small Heterodimer Partner (SHP/NR0B2) have a role in transcriptional repression of lipogenesis. Comparative genomic analyses reveal that most of the SHP cistrome, including lipogenic genes repressed by FGF19, have overlapping CpG islands. FGF19 treatment or SHP overexpression in mice inhibits lipogenesis in a DNA methyltransferase-3a (DNMT3A)-dependent manner. FGF19-mediated activation of SHP via phosphorylation recruits DNMT3A to lipogenic genes, leading to DNA methylation and gene repression. In non-alcoholic fatty liver disease (NAFLD) patients and obese mice, occupancy of SHP and DNMT3A and DNA methylation at lipogenic genes are low, with elevated gene expression. These results demonstrate that FGF15/19 represses hepatic lipogenesis by activating SHP and DNMT3A physiologically, which is likely dysregulated in NAFLD.

2020-09-23 | GSE158359 | GEO

Aortic arch profiling of Apoe knockout mice

Project description:Aortic arch profiling of Apoe-/- mice fed a high fat diet (HFD, Harlan Teklad 88137, 21% fat, 0.15% cholesterol) starting at 8 weeks of age for 8, 16, and 24 weeks. B6 mice fed HFD for 16 weeks starting at 8 weeks of age were used as controls. Apoe-/- mice were fed a high fat diet (HFD, Harlan Teklad 88137, 21% fat, 0.15% cholesterol) starting at 8 weeks of age for 8, 16, and 24 weeks. B6 mice fed HFD for 16 weeks starting at 8 weeks of age were used as controls. At each time point, 9 mice were studied. Mice were euthanized at each time point and whole aorta (from aortic root to renal bifurcation) of each mouse was immediately collected and flash-frozen in liquid N2. Mice were fasted overnight prior to euthanasia. the aortic arches of three mice in the same study group were pooled, resulting in three pools per study group.

2010-06-22 | E-GEOD-18443 | biostudies-arrayexpress

Renal Expression of Dahl SS/Jr (S) and Congenic Rats after 28 days of dietary salt elevation

Project description:The overlap of congenic regions in an earlier substitution mapping study suggested the location of two blood pressure quantitative trait loci (QTL)-containing regions in the q-terminus of rat chromosome 3, QTL1 and the more distal, QTL2. Male SS/jr rats and two congenic substrain rats S.R(D3Mco36-D3Mco46) and S.R(D3Mco36-D3Got166) were maintained on a low salt (0.4% NaCl Harlan Teklad diet TD7034) diet until 39-41 days of age and then fed an intermediate (2% NaCl Harlan Teklad diet TD94217) salt diet for 28 days. These 3 rat strains will be hereafter referred to as S, S.R(ET3x1), and S.R(ET3x2), respectively. Both congenic substrains carry SR/jr (R)-rat alleles for QTL2 on an S-rat genetic background, while S.R(ET3x2) also carries R-rat alleles for QTL1. Renal gene expression analysis was used to identify differentially expressed genes or genes with altered activity within the S.R(ET3x2) congenic region. Keywords: strain differences in response to dietary changes

2015-08-28 | GSE12423 | GEO

Renal Expression of Dahl SS/Jr (S) and Congenic Rats after 24 hours of Dietary Salt Loading

Project description:The overlap of congenic regions in an earlier substitution mapping study suggested the location of two blood pressure quantitative trait loci (QTL)-containing regions in the q-terminus of rat chromosome 3, QTL1 and the more distal, QTL2. Male SS/jr rats and two congenic substrain rats S.R(D3Mco36-D3Mco46) and S.R(D3Mco36-D3Got166) were maintained on a low salt (0.4% NaCl Harlan Teklad diet TD7034) diet until 39-41 days of age. These 3 rat strains will be hereafter referred to as S, S.R(ET3x1), and S.R(ET3x2), respectively. At 39-41 days of age, half of the rats from each strain were fed a high (4% NaCl Harlan Teklad diet TD83033) salt diet and water ad libitum for 24 hours. Both congenic substrains carry SR/jr (R)-rat alleles for QTL2 on an S-rat genetic background, while S.R(ET3x2) also carries R-rat alleles for QTL1. Renal gene expression analysis was used to identify differentially expressed genes or genes with altered activity within the S.R(ET3x2) congenic region. Keywords: strain differences in response to dietary changes

2015-08-28 | GSE12424 | GEO

Expression profiling of Brain tissue from C57BL/6J X C3H/HeJ)F2 and (C3H/HeJ X C57BL/6J)F2

Project description:The purpose of this experiment was to determine the expression traits in animals from F2 intercross of inbred strains C57BL/6J, C3H/HeJ. (N=309, 164 males and 145 females). Brain from 292 F2 female and male mice were generated by intercrossing F1 mice. Mice were fed chow diet containing 4% fat (Ralston-Purina Co., St. Louis, MO) until 8 weeks of age and then were placed on a high-fat "Western" diet containing 42% fat and 0.15%cholesterol (Teklad 88137, Harlan Teklad, Madison WI) for 12 weeks. At 20 weeks mice were sacrificed, after a 12-hour fast Brain tissues were dissected and flash frozen in LN2 and stored at -80Â°C.

2009-08-09 | E-GEOD-12798 | biostudies-arrayexpress

Expression profiling of Adipose tissue from C57BL/6J X C3H/HeJ)F2 and (C3H/HeJ X C57BL/6J )F2

Project description:The purpose of this experiment was to determine the expression traits in animals from F2 intercross of inbred strains C57BL/6J, C3H/HeJ. (N=309, 164 males and 145 females). Adipose from 295 F2 female and male mice were generated by intercrossing F1 mice. Mice were fed chow diet containing 4% fat (Ralston-Purina Co., St. Louis, MO) until 8 weeks of age and then were placed on a high-fat "Western" diet containing 42% fat and 0.15% cholesterol (Teklad 88137, Harlan Teklad, Madison WI) for 12 weeks. At 20 weeks mice were sacrificed, after a 12-hour fast adipose tissues were dissected and flash frozen in LN2 and stored at -80Â°C. Keywords=Genetics of Gene Expression Keywords Keywords=C57B1/J6 Keywords=C3H/HeJ

2009-08-09 | E-GEOD-11065 | biostudies-arrayexpress

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