The expression of genes involved in jejunal lipogenesis and lipoprotein synthesis is altered in morbidly obese subjects with insulin resistance

Gutiérrez-Repiso, Carolina; Rodríguez‐Pacheco, Francisca; García-Arnés, Juan Antonio; Valdés, Sergio; Gonzalo, Montserrat; Soriguer, Federico; Moreno-Ruiz, Francisco J.; Rodríguez‐Cañete, Alberto; Gallego-Perales, José L.; Alcaín‐Martínez, Guillermo; Vázquez‐Pedreño, Luis; López-Enríquez, Soledad; García‐Serrano, Sara; Garrido‐Sánchez, Lourdes; Garcı́a-Fuentes, Eduardo

doi:10.1038/labinvest.2015.115

Cited by 22 publications

(26 citation statements)

References 46 publications

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“…The study was undertaken in 45 morbidly obese subjects who underwent Roux-en-Y gastric bypass (RYGB) at baseline and 1, 3, 6 and 12 months after RYGB [3,5,22] (Table 1). The subjects were classified in three groups: two groups according to the homeostasis model assessment of insulin resistance (HOMA-IR) level (with low HOMA-IR value (<4.7) (MO-low-IR), n = 15) and with high HOMA-IR value (>4.7) (MO-high-IR, n = 15) (both groups without treatment for T2DM) and a third group (n = 15) with T2DM who were only receiving metformin treatment (MO-metf-T2DM) [3,5,23]. Subjects were excluded if they had T2DM and were receiving insulin treatment or other oral hypoglycaemic medications, had cardiovascular disease, acute inflammatory or infectious disease.…”

Section: Subjectsmentioning

confidence: 99%

“…Serum was separated and immediately frozen at −80 • C until analysis. Serum biochemical parameters were measured in duplicate, as previously described [3,5,6]. Changes in the variables due to RYGB were expressed as percentages and were calculated as (variable baseline − variable 1, 3, 6 or 12 months ) × 100/variable baseline [24].…”

Section: Laboratory Measurementsmentioning

confidence: 99%

“…Jejunal biopsy samples (n = 15 per group) were obtained during bariatric surgery, 40 cm from the ligament of Treitz [3,5,6]. The mucosa was washed with physiological saline solution, scraped, immediately frozen in liquid nitrogen and maintained at −80 • C until analysis.…”

Section: Jejunal Biopsy Samplesmentioning

confidence: 99%

“…A cell viability assay in jejunal biopsy samples (n = 6 per group) was performed in triplicate using the CellTiter-Glo ® Luminescent Cell Viability Assay (Promega, Southampton, UK) according to the manufacturer's instructions [5].…”

Section: Cell Viability In Jejunummentioning

confidence: 99%

“…Previous studies have shown the involvement of insulin resistance in the intestinal metabolism dysregulation [4]. However, changes in the human intestinal metabolism in insulin resistance and/or type 2 diabetes mellitus (T2DM) have not been explored in depth [3,[5][6][7]. Intestinal glucose-6 phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase-cytosolic form (PEPCK-c), which are involved in the gluconeogenesis pathway and in the control of endogenous glucose production [8], are targets of insulin [9].…”

Section: Introductionmentioning

confidence: 99%

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Jejunal Insulin Signalling Is Increased in Morbidly Obese Subjects with High Insulin Resistance and Is Regulated by Insulin and Leptin

Gutiérrez-Repiso

Ho-Plágaro

Santiago‐Fernández

et al. 2020

JCM

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Little is known about the jejunal insulin signalling pathways in insulin resistance/diabetes states and their possible regulation by insulin/leptin. We study in jejunum the relation between insulin signalling and insulin resistance in morbidly obese subjects with low (MO-low-IR) or with high insulin resistance (MO-high-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM), and the effect of insulin/leptin on intestinal epithelial cells (IEC). Insulin receptor substrate-1 (IRS1) and the catalytic p110β subunit (p110β) of phosphatidylinositol 3-kinase (PI3K) were higher in MO-high-IR than in MO-low-IR. The regulatory p85α subunit of PI3K (p85α)/p110β ratio was lower in MO-high-IR and MO-metf-T2DM than in MO-low-IR. Akt-phosphorylation in Ser473 was reduced in MO-high-IR compared with MO-low-IR. IRS1 and p110-β were associated with insulin and leptin levels. The improvement of body mass index (BMI) and HOMA-IR (homeostasis model assessment of insulin resistance index) after bariatric surgery was associated with a higher IRS1 and a lower p85α/p110β ratio. IEC (intestinal epithelial cells) incubation with a high glucose + insulin dose produced an increase of p85α and p110β. High dose of leptin produced an increase of IRS1, p85α and p110β. In conclusion, despite the existence of insulin resistance, the jejunal expression of genes involved in insulin signalling was increased in MO-high-IR. Their expressions were regulated mainly by leptin. IRS1 and p85α/p110β ratio was associated with the evolution of insulin resistance after bariatric surgery.

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Section: Subjectsmentioning

confidence: 99%

Section: Laboratory Measurementsmentioning

confidence: 99%

Section: Jejunal Biopsy Samplesmentioning

confidence: 99%

Section: Cell Viability In Jejunummentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Jejunal Insulin Signalling Is Increased in Morbidly Obese Subjects with High Insulin Resistance and Is Regulated by Insulin and Leptin

Gutiérrez-Repiso

Ho-Plágaro

Santiago‐Fernández

et al. 2020

JCM

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Different Expression of Duodenal Genes Related to Insulin Resistance Between Nonobese Women and Those with Severe Obesity

Ho-Plágaro

Santiago‐Fernández

Rodríguez‐Díaz

et al. 2020

Obesity

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Objective The study aim was to identify changes in duodenal gene expression associated with the development of insulin resistance according to the BMI of women. Methods Duodenal samples were assessed by microarray in four groups of women, nonobese women and women with severe obesity, with both low and high insulin resistance. Results There was a group of shared downregulated differentially expressed genes (DEGs) related to tissue homeostasis and antimicrobial humoral response in women with higher insulin resistance both with severe obesity and without obesity. In the exclusive DEGs found in severe obesity, downregulated DEGs related to the regulation of the defense response to bacterium and cell adhesion, involving pathways related to the immune system, inflammation, and xenobiotic metabolism, were observed. In the exclusive DEGs from nonobese women with higher insulin resistance, upregulated DEGs mainly related to the regulation of lipoprotein lipase activity, very low‐density lipoprotein particle remodeling, lipid metabolic process, antigen processing, and the presentation of peptide antigen were found. Conclusions Independent of BMI, higher insulin resistance was associated with a downregulation of duodenal DEGs mainly related to the immune system, inflammation, and xenobiotic metabolism. Also, intestinal lipoprotein metabolism may have a certain relevance in the regulation of insulin resistance in nonobese women.

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Gastric bypass elicits persistent gut adaptation and unique diabetes remission‐related metabolic gene regulation

Stefater‐Richards,

Panciotti,

Esteva

et al. 2024

Obesity

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ObjectiveWe have previously shown that early intestinal adaptation precedes and relates to metabolic improvement in humans after Roux‐en‐Y gastric bypass surgery (RYGB). We hypothesized that intestinal adaptation would persist at the 1‐year postoperative time point and that gene expression (GE) signatures would relate to type 2 diabetes remission, providing insight into potential mechanisms for intestinally mediated metabolic improvement after RYGB.MethodsWe determined GE by RNA sequencing in jejunum (Roux limb [RL]) collected from 28 patients before and 12 months after RYGB.ResultsGlobal GE from paired baseline and 1‐year jejunal samples did not separate according to clinical phenotype (type 2 diabetes remission, sustained weight loss). In general, GE was consistent with persistent RL remodeling, and microvilli were elongated by 39%. Remodeling was not attenuated in patients with lack of diabetes remission or with weight regain. Patients with diabetes remission demonstrated greater jejunal activation of lipogenesis‐related pathways driven by RXR, LXR, and SREBP.ConclusionsRL adaptation is a key feature of RYGB in all patients, likely reflecting the dramatic alterations to gastrointestinal anatomy, but jejunal lipogenesis appears to be more strongly activated in those patients with diabetes remission. Further study is needed to understand whether these pathways may drive metabolic remission after RYGB.

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The expression of genes involved in jejunal lipogenesis and lipoprotein synthesis is altered in morbidly obese subjects with insulin resistance

Cited by 22 publications

References 46 publications

Jejunal Insulin Signalling Is Increased in Morbidly Obese Subjects with High Insulin Resistance and Is Regulated by Insulin and Leptin

Jejunal Insulin Signalling Is Increased in Morbidly Obese Subjects with High Insulin Resistance and Is Regulated by Insulin and Leptin

Different Expression of Duodenal Genes Related to Insulin Resistance Between Nonobese Women and Those with Severe Obesity

Gastric bypass elicits persistent gut adaptation and unique diabetes remission‐related metabolic gene regulation

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