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Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE218931 | GEO | 2023/01/27

REPOSITORIES: GEO

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Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice.

Project description:Long non-coding RNAs (lncRNAs) are emerging important epigenetic regulators in metabolic processes. Whether they contribute to the metabolic effects of vertical sleeve gastrectomy (VSG), one of the most effective treatments for sustainable weight loss and metabolic improvement, is unknown. Herein, we identify a hepatic lncRNA Gm19619, which is strongly repressed by VSG but highly up-regulated by diet-induced obesity and overnight-fasting in mice. Forced transcription of Gm19619 in the mouse liver significantly promotes hepatic gluconeogenesis with the elevated expression of G6pc and Pck1. In contrast, AAV-CasRx mediated knockdown of Gm19619 in high-fat diet-fed mice significantly improves hepatic glucose and lipid metabolism. Mechanistically, Gm19619 is enriched along genomic regions encoding leptin receptor (Lepr) and transcription factor Foxo1, as revealed in chromatin isolation by RNA purification (ChIRP) assay and is confirmed to modulate their transcription in the mouse liver. In conclusion, Gm19619 may enhance gluconeogenesis and lipid accumulation in the liver.

| S-EPMC9883214 | biostudies-literature

Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice [ChIRP-Seq]

Project description:Long non-coding RNAs (lncRNAs) are emerging important epigenetic regulators in metabolic processes. Whether they contribute to the metabolic effects of vertical sleeve gastrectomy (VSG), one of the most effective treatments for sustainable weight loss and metabolic improvement, is unknown. Herein, we identified a hepatic lncRNA Gm19619, which was strongly repressed by VSG but highly up-regulated by diet-induced obesity and overnight-fasting in mice. Forced transcription of Gm19619 in the mouse liver significantly promoted hepatic gluconeogenesis with the elevated expression of G6pc and Pck1. In contrast, AAV-CasRx mediated knockdown of Gm19619 in HFD-fed mice significantly improved hepatic glucose and lipid metabolism. Mechanistically, Gm19619 was enriched along genomic regions encoding leptin receptor (Lepr) and the transcriptional factor Foxo1, as revealed in chromatin isolation by RNA purification (ChIRP) assay and was confirmed to modulate their transcription in the mouse liver. In conclusion, Gm19619 may enhance gluconeogenesis and lipid metabolism in the liver.

2023-01-27 | GSE218905 | GEO

Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice [RNA-Seq]

Project description:Long non-coding RNAs (lncRNAs) are emerging important epigenetic regulators in metabolic processes. Whether they contribute to the metabolic effects of vertical sleeve gastrectomy (VSG), one of the most effective treatments for sustainable weight loss and metabolic improvement, is unknown. Herein, we identified a hepatic lncRNA Gm19619, which was strongly repressed by VSG but highly up-regulated by diet-induced obesity and overnight-fasting in mice. Forced transcription of Gm19619 in the mouse liver significantly promoted hepatic gluconeogenesis with the elevated expression of G6pc and Pck1. In contrast, AAV-CasRx mediated knockdown of Gm19619 in HFD-fed mice significantly improved hepatic glucose and lipid metabolism. Mechanistically, Gm19619 was enriched along genomic regions encoding leptin receptor (Lepr) and the transcriptional factor Foxo1, as revealed in chromatin isolation by RNA purification (ChIRP) assay and was confirmed to modulate their transcription in the mouse liver. In conclusion, Gm19619 may enhance gluconeogenesis and lipid metabolism in the liver.

2023-01-27 | GSE218904 | GEO

Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice

Project description:Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice

| PRJNA906150 | ENA

Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice [ChIRP-Seq]

Project description:Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice [ChIRP-Seq]

| PRJNA906154 | ENA

Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice [RNA-Seq]

Project description:Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice [RNA-Seq]

| PRJNA906153 | ENA

Transcriptomics analysis of enteroendocrine cells following vertical sleeve gastrectomy

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-10-19 | GSE121490 | GEO

RNAseq Analysis of Mouse Stomach and Intestines Following Vertical Sleeve Gastrectomy

Project description:Bariatric surgery, an effective treatment for obesity and diabetes, leads to profound remodeling of whole body energy homeostasis. We utilized a mouse model of vertical sleeve gastrectomy (VSG), a common bariatric surgery as a tool to identify novel secreted proteins and peptides that might act as important metabolic regulators. We analyzed gene expression in the stomach and intestines following VSG or sham surgery in diet-induced obese mice and sought to identify differentially regulated genes encoding secreted proteins/peptides.

2017-10-14 | GSE104956 | GEO

Vertical sleeve gastrectomy improves ventilatory drive through a leptin-dependent mechanism.

Project description:Obesity hypoventilation syndrome (OHS) is a serious disorder characterized by daytime hypercapnia, disordered breathing, and a reduction in chemosensitivity. Vertical sleeve gastrectomy (VSG), a bariatric surgical procedure resulting in weight loss and weight-independent improvements in glucose metabolism, has been observed to substantially improve sleep-disordered breathing. However, it is unclear if the ventilatory effects of VSG are secondary to weight loss or the marked change in metabolic physiology. Using preclinical mouse models, we found that VSG leads to an improvement in the hypercapnic ventilatory response (HCVR) and reductions in circulating leptin levels independent of reductions in body mass, fat mass, and caloric intake. In the absence of leptin, VSG continues to improve body mass, fat mass, and glucose tolerance in ob/ob mice but no longer affects HCVR. However, the HCVR of ob/ob mice can be returned to wild-type levels with leptin treatment. These data demonstrate that VSG improves chemosensitivity and ventilatory drive via a leptin-dependent mechanism. Clinically, these data downgrade the relative contribution of physical, mechanical load in the pathogenesis of OHS, and instead point to physiological components of obesity, including alterations in leptin signaling, as key drivers in OHS.

| S-EPMC6485355 | biostudies-literature

Hepatic transcriptomic changes following equivalent weight loss by calorie restriction or vertical sleeve gastrectomy in mice with hepatic steatosis

Project description:Sleeve gastrectomy (VSG) leads to improvement in hepatic steatosis, associated with weight loss. The aims of this study were to investigate whether VSG leads to weight-loss independent improvements in liver steatosis in mice with diet-induced obesity (DIO); and to transcriptomically profile hepatic changes in mice undergoing VSG. Methods: Mice with DIO were treated with VSG, sham surgery with subsequent food restriction to weight-match to the VSG group (Sham-WM), or sham surgery with return to unrestricted diet (Sham-Ad lib). Hepatic transcriptomics were investigated at the end of the study period and treatment groups were compared with mice undergoing sham surgery only (Sham-Ad lib). Results: VSG led to much greater improvement in liver steatosis than Sham-WM (liver triglyceride mg/mg 2.5 ± 0.1, 2.1 ± 0.2, 1.6 ± 0.1 for Sham-AL, Sham-WM and VSG respectively; p=0.003). Homeostatic model assessment of insulin resistance was improved following VSG only (51.2 ± 8.8, 36.3 ± 5.3, 22.3 ± 6.1 for Sham-AL, Sham-WM and VSG respectively; p=0.03). The glucagon-alanine index, a measure of glucagon resistance, fell with VSG but was significantly increased in Sham-WM (9.8 ± 1.7, 25.8 ± 4.6 and 5.2 ± 1.2 in Sham Ad-lib, Sham-WM and VSG respectively; p=0.0003). Genes downstream of glucagon receptor signalling which govern fatty acid synthesis (Acaca, Acacb, Me1, Acyl, Fasn and Elovl6) were downregulated following VSG but upregulated in Sham-WM. Conclusion: Changes in glucagon sensitivity may contribute to weight-loss independent improvements in hepatic steatosis following VSG.

2024-03-13 | GSE225843 | GEO

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