Jejunum Inflammation in Obese and Diabetic Mice Impairs Enteric Glucose Detection and Modifies Nitric Oxide Release in the Hypothalamus

Duparc, Thibaut; Naslain, Damien; Colom, André; Muccioli, Giulio G.; Massaly, Nicolas; Delzenne, Nathalie M.; Valet, Philippe; Cani, Patrice D.; Knauf, Claude

doi:10.1089/ars.2010.3330

Cited by 39 publications

(50 citation statements)

References 36 publications

(51 reference statements)

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“…Ding et al (37) reported that conventionally raised specific-pathogen free C57BL/6J mice that were WT for the LDLR when fed a high-fat diet developed increased levels of TNF mRNA and showed increased activation of a NF-B green fluorescent protein reporter gene in the small intestine and colon compared with germ-free mice. Duparc et al (38) reported that obese db/db mice had increased levels of expression of iNOS, IL-1, and endoplasmic reticulum stress genes (Chop, Atf4) in the jejunum compared with lean animals. They also saw a trend to higher oxidative stress in the jejunum measured by TBARS for lipid peroxidation and NO-derived products, however they did not see an increase in NADPH oxidase or COX2 (24).…”

Section: Why Were the Changes Less In Wt Mice?mentioning

confidence: 99%

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Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD

Chattopadhyay

Navab

Hough

et al. 2016

Journal of Lipid Research

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This article is available online at http://www.jlr.orgOur laboratory, together with the University of California, San Diego group, pioneered the now widely accepted concept that oxidized phospholipids formed in the subendothelial space of the artery wall are responsible for initiating the early inflammatory response that is critical to the development of atherosclerosis (1-4). The recognition of oxidized phospholipids in the artery wall was established by using antibodies to oxidized phospholipids (5) and confirmed by our laboratory using MS (6). Oxidized phospholipids have been implicated in both pro-inflammatory and anti-inflammatory processes acting through multiple signaling pathways (7).We previously reported that adding 1 g of unsaturated (but not saturated) lysophosphatidic acid (LPA) to each gram of standard mouse chow induced dyslipidemia and systemic inflammation in LDL receptor (LDLR)-null mice similar to that seen when the mice were fed a Western diet (WD) (8,9). More recently, we demonstrated that the LPA-mediated dyslipidemia resulted in aortic atherosclerosis in LDLR-null mice that was similar in cellular characteristics to that seen on feeding these mice WD (10). Additionally, we presented evidence that in the enterocytes of

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Section: Why Were the Changes Less In Wt Mice?mentioning

confidence: 99%

“…Thus, the literature contains some scattered evidence that a high-fat diet can lead to intestinal inflammation in WT mice (37)(38)(39)(40)(41), and one report (42) suggests that gastric inflammation was worse in the absence of the LDLR. As shown in Fig.…”

Section: Why Were the Changes Less In Wt Mice?mentioning

confidence: 99%

Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD

Chattopadhyay

Navab

Hough

et al. 2016

Journal of Lipid Research

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“…Protocol is explained in details in Supplementary Materials and Methods section. Data are expressed as delta variation of H 2 O 2 release from basal as previously used for amperometric nitric oxide (NO) measurement (11,12).…”

Section: Real-time Amperometric H 2 O 2 Measurementsmentioning

confidence: 99%

Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes

Drougard

Duparc

Brénachot

et al. 2014

Antioxidants & Redox Signaling

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Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver glucose metabolism and glycemia. Results: We show that icv apelin injection stimulates liver glycogenolysis and gluconeogenesis via an over-activation of the sympathetic nervous system (SNS), leading to fasted hyperglycemia. The effect of central apelin on liver function is dependent of an increased production of hypothalamic reactive oxygen species (ROS). These data are strengthened by experiments using lentiviral vectormediated over-expression of apelin in hypothalamus of mice that present over-activation of SNS associated to an increase in hepatic glucose production. Finally, we report that mice fed a high-fat diet present major alterations of hypothalamic apelin/ROS signaling, leading to activation of glycogenolysis. Innovation/Conclusion: These data bring compelling evidence that hypothalamic apelin is one master switch that participates in the onset of diabetes by directly acting on liver function. Our data support the idea that hypothalamic apelin is a new potential therapeutic target to treat diabetes. Antioxid. Redox Signal. 20, 557-573.

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“…Using specific NO amperometric probes implanted directly into the hypothalamus of mice, our group has demonstrated that NO release is stimulated in response to the activation of enteric glucose sensors (25). Hypothalamic NO is known to cause increased blood flow in mice, which is associated with enhanced glucose utilization (12).…”

Section: G647mentioning

confidence: 99%

Glucosensing in the gastrointestinal tract: Impact on glucose metabolism

Fournel

Marlin

Abot

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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The gastrointestinal tract is an important interface of exchange between ingested food and the body. Glucose is one of the major dietary sources of energy. All along the gastrointestinal tube, e.g., the oral cavity, small intestine, pancreas, and portal vein, specialized cells referred to as glucosensors detect variations in glucose levels. In response to this glucose detection, these cells send hormonal and neuronal messages to tissues involved in glucose metabolism to regulate glycemia. The gastrointestinal tract continuously communicates with the brain, especially with the hypothalamus, via the gut-brain axis. It is now well established that the cross talk between the gut and the brain is of crucial importance in the control of glucose homeostasis. In addition to receiving glucosensing information from the gut, the hypothalamus may also directly sense glucose. Indeed, the hypothalamus contains glucose-sensitive cells that regulate glucose homeostasis by sending signals to peripheral tissues via the autonomous nervous system. This review summarizes the mechanisms by which glucosensors along the gastrointestinal tract detect glucose, as well as the results of such detection in the whole body, including the hypothalamus. We also highlight how disturbances in the glucosensing process may lead to metabolic disorders such as type 2 diabetes. A better understanding of the pathways regulating glucose homeostasis will further facilitate the development of novel therapeutic strategies for the treatment of metabolic diseases.glucosensing; glucose homeostasis; diabetes GLUCOSE REPRESENTS ONE of the major sources of energy circulating throughout the body. The tight and continuous control of glycemia in the face of fluctuations in glucose absorption, storage, and production is crucial for all living organisms. Not surprisingly, the gastrointestinal tract constitutes the first anatomic site for the detection of nutrients, including glucose. Glucose detection involves specialized cells referred to as glucosensors (21,44,64). These cells, which are present in the oral cavity as well as the small intestine, pancreas, and portal vein, express various glucose transporters and G proteincoupled receptors (GPCRs) implicated in the physiological response to glucosensing (21,44,64). Glucosensing by these cells evokes complex neural and endocrine responses that control glucose metabolism. Moreover, glucose detection in the gastrointestinal tract also transmits afferent nervous impulses to the brain, which, in turn, controls peripheral glucose utilization. Indeed, the brain, specifically the hypothalamus, is a key player in the regulation of glucosensing mechanisms. In addition to receiving information via the gut-brain axis, the hypothalamus also contains glucosensitive cells able to detect glucose (91). Upon the integration of these messages, the hypothalamus sends specific signals to the tissues involved in glucose metabolism via the autonomous nervous system (ANS).Metabolic disorders such as type 2 diabetes (T2D) are considered as ...

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Jejunum Inflammation in Obese and Diabetic Mice Impairs Enteric Glucose Detection and Modifies Nitric Oxide Release in the Hypothalamus

Cited by 39 publications

References 36 publications

Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD

Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD

Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes

Glucosensing in the gastrointestinal tract: Impact on glucose metabolism

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