Transcriptomic profiling of hepatic response to glucose intake during fasting and feeding states in a mouse model of metabolic dysfunction
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE295094 | GEO | 2026/05/31
REPOSITORIES: GEO
Similar Datasets
Project description:Interventions: Regular group:Same as regular group.;Water before operation group:No lavation and nasogastric intubation. Oral intake of water 250ml 1.5-2 hours before operation; others are the same as regular group. ;Fast track group:No lavation and nasogastric intubation and oral intake of water 250ml within 1.5-2 hours before operation; place nasojejunic feeding tube during operation; other approaches same as regular group. ;Regular group:Preoperative fasting 6-8 hours, nasogastric intubation before operation; early ambulation in 24-48 hours, removing catheter at 48 hour after operation and control blood sugar under 12 mmol/l.;Glucose before operation:No lavation and nasogastric intubation. Oral 5% glucose solution 250ml within 1.5-2 hours before operation; other treatment same as regular group. ;Fast track group:Place nasojejunic feeding tube in patients with gastric cancer during operation and others are the same as regular group.
Primary outcome(s): Length of hospital stay after operation
Study Design: Randomized parallel controlled trial
| 2672681 | ecrin-mdr-crc
Project description:Exercise training is a potent treatment of NAFLD and hepatic insulin resistance. Here we provide molecular information about the hepatic mitochondrial metabolism in mice when chronic overnutrition (high-energy diet (HED) for 6 weeks) is combined with exercise training. Training reduced the hepatic triacylglycerol content, fasting insulin, and reversed glucose intolerance. Training modified the hepatic mitochondrial proteome with a decrease in enzymes related to pyruvate metabolism and entry of acetyl-CoA into the TCA cycle. Transcriptome data revealed down-regulation of glucose oxidation and lipogenesis. The mitochondrial respiratory capacity of trained HED-fed mice is increased despite reduced content of complex I. Training decreased diacylglycerol species and JNK phosphorylation, both of which can induce insulin resistance. Increased mitochondrial mass and oxidative capacity of the trained muscle further unburdens the liver from substrate overload. Together, when high fat and carbohydrate intake in mice is accompanied by exercise, the decline of mitochondrial function and insulin resistance can be prevented by modification of mitochondrial acetyl-CoA metabolism.
2022-02-16 | PXD024308 | Pride
Project description:The liver acts as a master regulator of metabolic homeostasis in part by performing gluconeogenesis. This process is dysregulated in type 2 diabetes, leading to elevated hepatic glucose output. The parenchymal cells of the liver (hepatocytes) are heterogeneous, existing on an axis between the portal triad and the central vein, and perform distinct functions depending on location in the lobule. Here, using single cell analysis of hepatocytes across the liver lobule, we demonstrate that gluconeogenic gene expression (Pck1 and G6pc) is relatively low in the fed state and gradually increases first in the periportal hepatocytes during the initial fasting period. As the time of fasting progresses, pericentral hepatocyte gluconeogenic gene expression increases, and following entry into the starvation state, the pericentral hepatocytes show similar gluconeogenic gene expression to the periportal hepatocytes. Similarly, pyruvate-dependent gluconeogenic activity is approximately 10-fold higher in the periportal hepatocytes during the initial fasting state but only 1.5-fold higher in the starvation state. In parallel, starvation suppresses canonical beta-catenin signaling and modulates expression of pericentral and periportal glutamine synthetase and glutaminase, resulting in an enhanced pericentral glutamine-dependent gluconeogenesis. These findings demonstrate that hepatocyte gluconeogenic gene expression and gluconeogenic activity are highly spatially and temporally plastic across the liver lobule, underscoring the critical importance of using well-defined feeding and fasting conditions to define the basis of hepatic insulin resistance and glucose production.
2024-11-14 | PXD051593 | Pride
Project description:Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy men ingested saturated (SFA) or poly unsaturated (PUFA) fat-rich diets for six weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diets increased fat oxidation potential in muscle. Hepatic insulin clearance increased, while glucose production, de novo lipogenesis and plasma triacylglycerol decreased. High fat intake changed the plasma proteome in immune-supporting direction and the gut microbiome displayed changes at taxonomical and functional level with PUFA. In mice, eucaloric feeding of human PUFA and SFA diets lowered hepatic triacylglycerol content compared to low-fat fed control mice, and induced adaptations in the liver supportive of decreased gluconeogenesis and lipogenesis. Intake of fat-rich diets thus induces extensive metabolic adaptations enabling disposition of dietary fat without metabolic complications.
2018-10-11 | PXD010516 | Pride
Project description:Insulin integrates hepatic glucose and lipid metabolism, directing nutrients to storage as glycogen and triglyceride. In type 2 diabetes, levels of the former are low and the latter are exaggerated, posing a pathophysiologic and therapeutic conundrum. A branching model1 of insulin signaling, with FoxO1 presiding over glucose production2-5 and Srebp–1c regulating lipogenesis,6-8 provides a potential explanation. Here we illustrate an alternative mechanism that integrates glucose production and lipogenesis under the unifying control of FoxO. Liver–specific ablation of three FoxOs (L–FoxO1,3,4) prevents the induction of glucose–6–phosphatase and the repression of glucokinase during fasting, thus increasing lipogenesis at the expense of glucose production. We document a similar pattern in the early phases of diet-induced insulin resistance, and propose that FoxOs are required to enable the liver to direct nutritionally derived carbons to glucose vs. lipid metabolism. Our data underscore the heterogeneity of hepatic insulin resistance during progression from the metabolic syndrome to overt diabetes, and the conceptual challenge of designing therapies that curtail glucose production without promoting hepatic lipid accumulation. We used microarrays to detail the change of gene expression in liver after knocking out FoxO1,3 and 4. Liver tissue samples were collected from hepatocyte- specific triple FoxO(1,3, and 4) KO and their littermates control (WT) mice after fasting (22 h) or refeeding (4 h). Gene expression was analyzed by microarray. Mice were on a mixed background of C57BL/6J and 129.
2014-08-20 | E-GEOD-60527 | biostudies-arrayexpress
Project description:Low-carbohydrate, high-fat diets under eucaloric conditions are associated with several health-beneficial metabolic effects in humans, particularly in the liver. We recently observed that apolipoprotein A-IV (apoA-IV), a highly abundant apolipoprotein, was among the most upregulated proteins in the circulation after six weeks of high fat intake in humans. However, the dietary regulation of apoA-IV and the potential effects of apoA-IV on regulation of glucose- and lipid metabolism remain to be fully established. We here demonstrate in healthy human individuals that both short- and long-term high-fat intake increased fasting plasma apoA-IV concentrations by up to 54%, while high carbohydrate intake suppressed plasma apoA-IV concentrations. In mice, administration of apoA-IV acutely lowered blood glucose levels in lean and obese mice. Interestingly, this was related to a dual mechanism, involving both inhibition of hepatic glucose production and increased glucose uptake into white and brown adipose tissues. In addition to an effect on hepatic glucose production, the apoA-IV-induced liver proteome revealed increased capacity for lipoprotein clearance. The effects of apoA-IV in the liver and adipose tissues were obtained concomitant with increased whole-body fatty acid oxidation. Upon glucose stimulation, an improvement in glucose tolerance by apoA-IV administration was related to potentiation of glucose-induced insulin secretion, while apoA-IV inhibited glucagon secretion ex vivo in islets. In conclusion, we find that ApoA-IV is potently increased by the intake of fat in humans, and that several beneficial metabolic effects, previously associated with high fat intake in humans, are mimicked by administration of apoA-IV protein to mice.
2025-05-07 | PXD055918 | Pride
Project description:The circadian rhythms influence the metabolic activity from molecular level to tissue, organ, and host level. Disruption of the circadian rhythms manifests to the host's health as metabolic syndromes, including obesity, diabetes, and elevated plasma glucose, eventually leading to cardiovascular diseases. Therefore, it is imperative to understand the mechanism behind the relationship between circadian rhythms and metabolism. To start answering this question, we propose a semimechanistic mathematical model to study the effect of circadian disruption on hepatic gluconeogenesis in humans. Our model takes the light-dark cycle and feeding-fasting cycle as two environmental inputs that entrain the metabolic activity in the liver. The model was validated by comparison with data from mice and rat experimental studies. Formal sensitivity and uncertainty analyses were conducted to elaborate on the driving forces for hepatic gluconeogenesis. Furthermore, simulating the impact of Clock gene knockout suggests that modification to the local pathways tied most closely to the feeding-fasting rhythms may be the most efficient way to restore the disrupted glucose metabolism in liver.
2024-09-02 | BIOMD0000001005 | BioModels
Project description:High intakes of carbohydrates, particularly sucrose, in Western societies are associated with the development of non-alcoholic fatty liver (NAFL) and diabetes mellitus. It is unclear whether this is related to the carbohydrate quantity or the hormonal responses, particularly Glucose-dependent Insulinotropic Polypeptide (GIP) which is released in the proximal intestine. We, therefore, used the glucose-fructose dimer as proximally resorbed, 1,4-linked sucrose or distally resorbed 1,6-linked palatinose. Palatinose compared to sucrose, indeed, resulted in slower glucose absorption and reduced postprandial insulin and GIP levels. After 22 weeks of isocaloric diets, palatinose feeding prevented hepatic steatosis (48.5%) compared to sucrose and improved glucose tolerance, without differences in body composition and food intake. Ablation of GIP receptor (GIPR) signaling in Gipr-/- mice completely prevented the deleterious metabolic effects of sucrose feeding. Furthermore, our microarray analysis indicated that sucrose increased the hepatic expression of Suppressor of Cytokine Signaling 2 (SOCS2), which is involved in the growth hormone signaling pathway and participates in the development of NAFL. Our results suggest that the site of glucose absorption and the GIP response determine liver fat accumulation and insulin resistance. GIP may play a role in sucrose induced fatty liver by regulating the expression of SOCS2. Expression data from liver tissue of mice fed with isocaloric diets containing either sucrose or palatinose
2014-12-05 | E-GEOD-54723 | biostudies-arrayexpress
Project description:Exercise training is a potent treatment of NAFLD and hepatic insulin resistance. Here we provide molecular information about the hepatic mitochondrial metabolism in mice when chronic overnutrition (high-energy diet (HED) for 6 weeks) is combined with exercise training. Training reduced the hepatic triacylglycerol content, fasting insulin, and reversed glucose intolerance. Training modified the hepatic mitochondrial proteome with a decrease in enzymes related to pyruvate metabolism and entry of acetyl-CoA into the TCA cycle. Transcriptome data revealed down-regulation of glucose oxidation and lipogenesis. The mitochondrial respiratory capacity of trained HED-fed mice is increased despite reduced content of complex I. Training decreased diacylglycerol species and JNK phosphorylation, both of which can induce insulin resistance. Increased mitochondrial mass and oxidative capacity of the trained muscle further unburdens the liver from substrate overload. Together, when high fat and carbohydrate intake in mice is accompanied by exercise, the decline of mitochondrial function and insulin resistance can be prevented by modification of mitochondrial acetyl-CoA metabolism.
2021-10-15 | GSE167046 | GEO
Project description:Paternal exposure to nicotine has been linked to altered metabolic phenotypes in offspring, yet the underlying mechanisms and sex-specific outcomes remain elusive. In this study, we investigated the effects of paternal nicotine exposure on glucose metabolism, and adipose tissue and liver transcriptomic profiles in male and female offspring. Despite no differences in body weight during early postnatal life, female offspring displayed lower fasting glucose and reduced glucose levels during glucose tolerance tests, without alterations in insulin sensitivity. These effects were accompanied by decreased circulating insulin and upregulation of genes involved in the insulin signaling pathway in gonadal white adipose tissue (gWAT), consistent with enhanced glucose uptake capacity. In contrast, male offspring showed no overt changes in glucose tolerance or insulin sensitivity, despite reduced plasma insulin and glucagon levels. In male offspring, liver transcriptomic analyses revealed downregulation of glucagon signaling, insulin resistance, and PPARα pathways, suggesting impaired fasting adaptation and reduced hepatic catabolic capacity. Collectively, these findings demonstrate that paternal nicotine exposure induces sex-dependent metabolic reprogramming, with pronounced effects on glucose homeostasis in females and transcriptional signatures of reduced fasting resilience in males. These results identify the liver and adipose tissue as key targets of paternal nicotine exposure in the offspring and underscore the need for longitudinal studies to determine whether these alterations predispose offspring to metabolic disease across the lifespan
2026-03-18 | GSE313674 | GEO