Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA124891 | ENA |
REPOSITORIES: ENA
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Project description:In the present study we tested the hypothesis that male and female rat livers respond differently to a change in nutrient availability or to insulin treatment. We compared hepatic gene expression, hepatic glycogen and glucose output, insulin sensitivity and amino acids, using healthy rats. Keywords: Hepatic gene expression, sex-differences
2011-03-01 | GSE20601 | GEO
Project description:In the present study we tested the hypothesis that male and female rat livers respond differently to a change in nutrient availability or to insulin treatment. We compared hepatic gene expression, hepatic glycogen and glucose output, insulin sensitivity and amino acids, using healthy rats. Keywords: Hepatic gene expression, sex-differences Two-condition experiment. Biological replicates: 4 male rat livers from rats on a standard diet and 4 female rat livers from rats on a standard diet. One replicate per array.
2011-03-01 | E-GEOD-20601 | biostudies-arrayexpress
Project description:Sex-differences in the control of gluconeogenesis and hepatic glucose output in rats
| PRJNA107731 | ENA
Project description:Like other per- and polyfluoroalkyl substances (PFAS), toxicity studies for short-chain HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate) indicate the liver is the primary target of toxicity in rodents. However, neonatal mortality and decreased birth weight were also reported in rats following oral exposure to HFPO-DA in utero. Exposure-related effects in neonatal rats including hypoglycemia, decreased liver glycogen, and perturbed hepatic gene expression of glucose metabolism and peroxisome proliferator activated receptor (PPAR) pathways also accompanied these findings. A putative rodent-specific adverse outcome pathway (AOP) network was recently developed using these endpoints and assessed for its applicability to PFAS. AOP 1 in this putative AOP network consists of PPARα activation as one of multiple initiating events, and placental insufficiency, neonatal hepatic glycogen deficit, and hypoglycemia as key events leading to neonatal mortality and lower birth weight. To further inform AOP 1 of this putative AOP network and investigate whether this altered carbohydrate metabolism liver phenotype observed in rat neonates also occurs in HFPO-DA-exposed pregnant and non-pregnant adult rats, transcriptomic analysis and glycogen staining were performed on female rat livers from a 15-d developmental or 90-d subchronic toxicity study. HFPO-DA-mediated changes in hepatic gene expression in female rats were consistent with PPAR signaling. Changes in hepatic glycogen content and glucose metabolism-related gene expression were independent of HFPO-DA exposure, indicating that the altered carbohydrate metabolism phenotype observed in neonatal livers does not occur in adult female rats, regardless of pregnancy status. Therefore, key events in this AOP for neonatal mortality and lower birthweight are likely to directly affect the perinatal rat and are not expected to affect the maternal rat liver. Findings from this study were consistent with previous mechanistic studies supporting the rodent-specific PPARα mode of action for HFPO-DA-mediated liver effects in rodents.
2025-10-31 | GSE291412 | GEO
Project description:Skeletal muscle is not only a primary site for glucose uptake and storage, but also a reservoir for amino acids stored as protein. How the metabolism of these two fuels is coordinated in skeletal muscle is incompletely understood. Here, we demonstrate that interferon regulatory factor 4 (IRF4) integrate glucose and amino acids flux by regulating glycogen synthesis and branched-chain-amino acid (BCAA) metabolism in skeletal muscle. Mice with IRF4 specifically knocked out in skeletal muscle (MI4KO) showed elevated plasma BCAAs and skeletal muscle glycogen content, decreased adiposity and body weight, along with increased energy expenditure, remarkable improvements in glucose and insulin tolerance, and protection from diet-induced obesity (DIO). Loss of IRF4 caused downregulation of the mitochondrial branched-chain aminotransferase isozyme (BCATm) in myocytes, which encodes for the enzyme catalyzing the first step of BCAA metabolism. Lack of IRF4 also led to the upregulation of protein targeting to glycogen (PTG), which is associated with enhanced mitochondrial Complex II activity and mitochondria number. Additionally, overexpression of IRF4 in skeletal muscle caused obesity and reduced exercise capacity. Mechanistically, we found that IRF4 directly regulates both BCATm and PTG expression, and that overexpression of BCATm can partially reverse the effects of IRF4 deletion. These studies establish IRF4 as a novel driver of both glucose and BCAA metabolism in skeletal muscle.
2019-08-30 | GSE136623 | GEO
Project description:We have previously shown that in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-elicited NAFLD progression, central carbon, glutaminolysis and serine/folate metabolism are reprogrammed to support NADPH production and ROS defenses. To further investigate underlying dose-dependent responses associated with TCDD-induced fibrosis, female C57BL/6 mice were gavaged with TCDD every 4 days (d) for 28d or 92d. RNA-Seq, ChIP-Seq (2hr), and 28d metabolomic (urine, serum, and hepatic extract) analyses were conducted with complementary serum marker assessments at 92d. Additional vehicle and 30 µg/kg treatment groups were allowed to recover for 36d following the 92d treatment regimen to examine recovery from TCDD-elicited fibrosis. Histopathology revealed dose-dependent increases in hepatic fat accumulation, inflammation, and periportal collagen deposition at 92d, with increased fibrotic severity in the recovery group. Serum proinflammatory and profibrotic interleukins-1β, -2, -4, -6, and -10, as well as TNFα and IFNγ, exhibited dose-dependent induction. An increase in glucose tolerance was observed with a concomitant 3.0-fold decrease in hepatic glycogen linked to increased ascorbic acid biosynthesis and proline metabolism, consistent with increased fibrosis. RNA-Seq identified differential expression of numerous matrisome genes including an 8.8-fold increase in Tgfb2 indicating myofibroblast activation. Further analysis suggests reprogramming of glycogen, ascorbic acid, and amino acid metabolism in support of collagen deposition and the use of proline as a substrate for ATP production via the proline cycle. Conclusion: In addition to metabolic reprogramming in support of NADPH production for ROS defense, we demonstrate that glycogen, ascorbic acid, and amino acid metabolism are also reorganized to support remodeling of the extracellular matrix, progressing to hepatic fibrosis in response to chronic injury from TCDD.
2016-09-01 | GSE81990 | GEO
Project description:Goals of the Study:; 1. Assess the scope of arginine-responsive hepatic gene expression using in vitro rat models. 2. Compare normal and tumorigenic cells; 3. Identify potentially novel genes and pathways that may be subject to amino acid (arginine) regulation; Background: We previously reported that mRNA levels of the tumor associated glycoprotein amino acid transporter TA1/LAT1/ CD98 light chain arginine increase in normal hepatic cells under low arginine conditions while levels are constitutive and high in hepatic tumor cells. This suggested LAT1 amino acid response was associated with the normal hepatic phenotype and lost in carcinogenesis and may impact cell growth and survival in the tumor microenvironment. We sought to investigate how many and what types of genes are responsive to a change in arginine levels over 18 hrs using an in vitro model system. Experimental design:; Differential gene expression was determined by microarrays using samples from triplicates of normal and transformed cells subjected to 18 hour arginine-deprivation compared to controls
2007-10-08 | E-GEOD-2275 | biostudies-arrayexpress
Project description:We assessed the impact of glucose transporter Glut2 gene inactivation in adult mouse liver (LG2KO mice). This suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was normal early after Glut2 inactivation but intolerance developed at later time. This was caused by progressive impairment of glucose-stimulated insulin secretion even though beta-cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinate down-regulation of cholesterol biosynthesis genes in LG2KO mice. This was associated with reduced hepatic cholesterol in fasted mice and a 30 percent reduction in bile acid production. We showed that chronic bile acids or FXR agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from fxr-/- mice. Collectively, our data show that glucose sensing by the liver controls beta-cell glucose competence, through a mechanism that likely depends on bile acid production and action on beta-cells. three replicates each of ps_ctrl_refed, ps_tamox_refed, ps_ctrl_fasted, ps_tamox_fasted
2013-01-18 | E-GEOD-43581 | biostudies-arrayexpress
Project description:Objective: Activation of the liver glucagon receptor (GCGR) promotes amino acid catabolism, which provides substrate for glucose production. Inhibition of the receptor downregulates hepatic amino acid catabolism, leading to increases in circulating amino acid levels. Amino acids serve as a potent growth factor for pancreatic alpha cells, where glucagon is produced. Thus, GCGR inhibition-induced hyperaminoacidemia causes alpha cell hyperplasia. This liver-alpha cell feedback loop, mediated by glucagon and amino acids, has been demonstrated across species, including humans. This study was designed to delineate hepatic signaling molecules that lie downstream of GCGR and mediate the liver-alpha cell loop. Methods: We used AAV8-shRNA to knock down GCGR signaling molecules, the G-coupled protein GNAS and two GNAS downstream effectors, PKA and EPAC2 (RAPGEF4), in the liver of diet-induced obese (DIO) mice. We monitored plasma amino acid and blood glucose levels and conducted pancreas histology to derive alpha and beta cell mass. We performed liver RNA-sequencing to assess expression of glucose and amino acid metabolism genes. To examine the contribution of PKA in changes associated with GCGR inhibition, we knocked down PRKAR1A, a major inhibitory subunit of PKA, to activate PKA in liver of mice administered with GCGR blocking or control antibody. Results: Comparable suppression of hepatic amino acid catabolism gene expressions, increases in plasma amino acid levels and alpha cell hyperplasia were observed in mice with hepatic knockdown of GCGR, GNAS, and PKA. Hepatic EPAC2 knockdown did not affect amino acid metabolism or alpha cell mass in mice. Mice with hepatic PKA activation alone developed hypoaminoacidemia, hypoglucagonemia and reduced alpha cell mass. Administering GCGR blocking antibody to the mice did not alter the abnormalities. Conclusions: Hepatic PKA activation in mice fully overrides the effect of GCGR inhibition on amino acids and alpha cells. In the liver, GCGR signals through PKA to control amino acid metabolism and pancreatic alpha cell mass. Hepatic PKA plays a critical role in the liver-alpha cell loop, mediated by circulating glucagon and amino acids.
2025-05-30 | GSE268864 | GEO
Project description:Postoperative insulin resistance refers to the phenomenon that the body’s glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery.
There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.
| 2744698 | ecrin-mdr-crc