Gene expression profile in the liver of insulin-deficient mice with icv leptin administration
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE48598 | GEO | 2013/09/03
SECONDARY ACCESSION(S): PRJNA210775
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of gene expression in the liver of insulin-deficient mice regulated by icv leptin administration. Control group received icv PBS administration. Icv leptin administration ameliorates hyperglycemia in insulin-deficient mice. Our transcriptome data provides important aspects of the leptin’s anti-type 1 diabetes action. Mice were harvested 10 days after icv leptin administration (25ng/0.11uL/hour). Liver samples were quickly removed, frozen in liquid nitrogen and subsequently stored at –80ºC. RNAs were extracted by Qiagen mRNA extract kits (RNeasy plus). gDNA was eliminated in this procedure by gDNA eliminator column, which is included in Qiagen mRNA extract kits. Genomics and Microarray Core Facility at UT-Southwestern (http://microarray.swmed.edu/) checked RNA quality with Bioanalyzer Chip and processed the samples for hybridization with Illumina Mouse-6 V2 BeadChip (Illumina Inc., San Diego, CA).
2013-09-03 | E-GEOD-48598 | biostudies-arrayexpress
Project description:Leptin monotherapy (i.e. without the use of administered insulin and/or any other molecule) corrects ID-induced metabolic aberrancies and promotes survival of insulin deficient rodents. These results generated great interest in the possibility of treating insulin deficient patients with leptin and/or molecule(s) underlying its beneficial effects. Hence, with the goal of identifying circulating molecule(s) underlying the advantageous effect of leptin we performed quantitative proteomic analysis of plasma and identified S100A9 as a putative peripheral mediator of leptin action. Here, to identify circulating molecule(s) underlying the advantageous effect of leptin we compared the results obtained by quantitative proteomic analysis of plasma between 2 groups of mice: streptozotocin (STZ)-treated mice that underwent intracerebroventricular (icv) leptin treatment for 12 days (STZ-Leptin) and ii) STZ-treated mice that underwent icv leptin treatment for 10 days and were withdrawn from leptin treatment for the following two days (STZ-Leptin-STOP). STZ treatment led to a massive loss of pancreatic insulin-producing β-cells, diminished pancreatic Proinsulin mRNA level, and caused severe insulinopenia, and hyperglycemia. icv leptin administration normalized hyperglycemia. However, two days after leptin delivery was halted hyperglycemia reappeared. We hypothesized that change in plasmatic protein(s) content could underlie re-emergence of hyperglycemia following decrease of leptin action.
2019-07-12 | PXD013466 | Pride
Project description:The purpose of this study was to identify leptin target genes and subsequent pathways correlated with leptin-mediated weight loss. We utilized the microarray technology to compare two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We report here the impact of central and peripheral administration of leptin on food intake, body weight and body fat composition in ob/ob mice. We also report hepatic gene expression changes caused by central versus peripheral leptin administration. Keywords: comparison Leptin deficient (ob/ob) mice were continuously administered leptin over 12-days using central (intracerebroventricular) or peripheral (subcutaneous) route of administration. Liver RNA was extracted and hybridized to Illumina microarrays and gene expression data was analyzed. The global gene expression profiles were compared after the central and peripheral leptin treatments in ob/ob mice and C57BL6 mice were used for the baseline gene expression.
2010-11-10 | E-GEOD-20878 | biostudies-arrayexpress
Project description:Leptin-responsive genes in the pathway of a leptin signal from the hypothalamus to the liver has not been detected. We used microarray to detailed the expression of gene in liver in the status of leptin deficiency, and leptin administration. As leptin deficient status, we use Lepmkyo/Lepmkyo rats or Lepob/Lepob mice and their wild type littermates. Recombinant murine leptin (1 microg/mg) and saline was intraperitonealy administrated in 20 weeks old Lepob/Lepob mice and their control littermates, and 20 weeks old Lepmkyo/Lepmkyo rats and their control littermates. In order to detect the early response genes whose expression level were changed before the food intake and body weight would change, we took liver samples 6 hours after administration.
2012-11-28 | E-GEOD-42532 | biostudies-arrayexpress
Project description:Leptin-responsive genes in the pathway of a leptin signal from the hypothalamus to the liver has not been detected. We used microarray to detailed the expression of gene in liver in the status of leptin deficiency, and leptin administration. As leptin deficient status, we use Lepmkyo/Lepmkyo rats or Lepob/Lepob mice and their wild type littermates.
2012-11-28 | GSE42532 | GEO
Project description:The purpose of this study was to identify leptin target genes and subsequent pathways correlated with leptin-mediated weight loss. We utilized the microarray technology to compare two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We report here the impact of central and peripheral administration of leptin on food intake, body weight and body fat composition in ob/ob mice. We also report hepatic gene expression changes caused by central versus peripheral leptin administration. Keywords: comparison
2010-11-10 | GSE20878 | GEO
Project description:Gene expression profile in the liver of insulin-deficient mice with icv leptin administration
| PRJNA210775 | ENA
Project description:Population based studies have established that androgen deficiency in males correlates with type 2 diabetes, visceral adiposity, and metabolic syndrome. Androgen therapy has been investigated as a possible treatment regime to combat these disorders. However, the molecular mechanism of androgen effects on these diseases still remain poorly understood. The zucker diabetic fatty (ZDF) rat, containing a mutation in the leptin receptor, is a well-investigated model of obesity and type 2 diabetes. Male rats are characterized as androgen deficient and spontaneously develop obese, hyperlipidemia, hyperglycemia and hyperinsulinemia. In this study, we used ZDF male rats as a model of metabolic syndrome to investigate the effects of testosterone administration on the development of the metabolic conditions. Methods: Male ZDF rats at six week of age were randomly divided into two groups and administered testosterone undecanoate(TU) or vehicle alone every three days for three weeks. After three weeks, overnight fasted blood glucose and insulin concentrations were significantly higher and glucose tolerance and insulin sensitivity were impaired in TU treated ZDF rats compared to vehicle controls. Moreover, increased serum triglycerides and VLDL were observed in TU treated rats. To further explore the observed metabolic changes in TU treated ZDF rats, whole-genome microarray analysis were performed on isolated liver mRNA. Results: Array analysis revealed that many hepatic lipogenic genes were increased in male ZDF rat livers treated with TU. Interestingly, SREBP-1c, a key transcriptional activator of lipogenic genes and PGC-1 , an activator of SREBP-1c were induced while small heterodimer partner, a transcriptional inhibitor of lipogenic genes was suppressed by TU treatment. Exploring signaling pathways for these effects, we observed that the hepatic activated forms of STAT3 and AMPK, two known inhibitors of hepatic lipogenesis, were decreased in TU treated rat. Moreover, we observed that DHT could block the induction of STAT3 and AMPK phosphorylation in treated primary human hepatocytes. Preliminarily, in the leptin receptor positive zucker diabetic lean male rats, we observed that TU treatment has an oppose effect on the hepatic lipogenic genes, suggesting that hepatic leptin signaling may influence androgen signaling. Further insight into the relationship between androgen deficiency and the leptin system may help improve treatment of the metabolic syndrome. Population based studies have established that androgen deficiency in males correlates with type 2 diabetes, visceral adiposity, and metabolic syndrome. Androgen therapy has been investigated as a possible treatment regime to combat these disorders. However, the molecular mechanism of androgen effects on these diseases still remain poorly understood. The zucker diabetic fatty (ZDF) rat, containing a mutation in the leptin receptor, is a well-investigated model of obesity and type 2 diabetes. Male rats are characterized as androgen deficient and spontaneously develop obese, hyperlipidemia, hyperglycemia and hyperinsulinemia. In this study, we used ZDF male rats as a model of metabolic syndrome to investigate the effects of testosterone administration on the development of the metabolic conditions. Two-condition experiment. (1) lean ZDF rats (control) vs. lean ZDF rats (testosterone treated). (2) obese ZDF rats (control) vs. obese ZDF rats (testosterone treated). Biological replicates: 4 control replicates, 4 treated replicates.
2012-09-02 | E-GEOD-23941 | biostudies-arrayexpress
Project description:Timed-feeding leads to adipose browning, although the integrative mechanisms for the same remain unclear. Here we show that twice-a-nocturnal (TAN) feeding causes biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed-feeding. Insulin and leptin surges lead to marked cellular, functional and metabolic remodeling of sWAT resulting in increased energy expenditure. Single-cell RNAseq analyses and flow cytometry reveal a role for insulin and leptin surges in ILC2 recruitment and sWAT browning, since depleting leptin or blocking insulin receptor signaling or ILC2 cell recruitment, each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day co-injections is sufficient to favorably remodel innervated sWAT. Indeed, innervation is necessary for sWAT remodeling since denervation of sWAT, but not BAT, blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, timed feeding reorganizes nutrient-sensitive pathways to remodel sWAT, which drives the metabolic benefits of timed-feeding.
2024-04-15 | GSE263899 | GEO
Project description:Timed-feeding leads to adipose browning, although the integrative mechanisms for the same remain unclear. Here we show that twice-a-nocturnal (TAN) feeding causes biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed-feeding. Insulin and leptin surges lead to marked cellular, functional and metabolic remodeling of sWAT resulting in increased energy expenditure. Single-cell RNAseq analyses and flow cytometry reveal a role for insulin and leptin surges in ILC2 recruitment and sWAT browning, since depleting leptin or blocking insulin receptor signaling or ILC2 cell recruitment, each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day co-injections is sufficient to favorably remodel innervated sWAT. Indeed, innervation is necessary for sWAT remodeling since denervation of sWAT, but not BAT, blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, timed feeding reorganizes nutrient-sensitive pathways to remodel sWAT, which drives the metabolic benefits of timed-feeding.
2024-04-17 | GSE264173 | GEO