Three of a kind: Control of the expression of liver-expressed antimicrobial peptide 2 (leap2) by the endocannabinoidome and the gut microbiome

The endocannabinoidome (expanded endocannabinoid system, eCBome)-gut microbiome (mBIome) axis plays a fundamental role in the control of energy intake and processing. The liver-expressed antimicrobial peptide 2 (LEAP2) is a recently identified molecule acting as an antagonist of the ghrelin receptor and hence a potential effector of energy metabolism, also at the level of the gastrointestinal system. Here we investigated the role of the eCBome-gut mBIome axis in the control of the expression of LEAP2 in the liver and, particularly, the intestine. We confirm that the small intestine is a strong contributor to the circulating levels of LEAP2 in mice, and show that: (1) intestinal Leap2 expression is profoundly altered in the liver and small intestine of 13 week-old germ-free (GF) male mice, which also exhibit strong alterations in eCBome signaling; fecal microbiota transfer (FMT) from conventionally raised to GF mice completely restored normal Leap2 expression after 7 days from this procedure; in 13 week-old female GF mice no significant change was observed; (2) Leap2 expression in organoids prepared from the mouse duodenum is elevated by the endocannabinoid noladin ether, whereas in human Caco-2/15 epithelial intestinal cells it is elevated by PPARγ activation by rosiglitazone; (3) Leap2 expression is elevated in the ileum of mice with either high-fat diet—or genetic leptin signaling deficiency—(i.e., ob/ob and db/db mice) induced obesity. Based on these results, we propose that LEAP2 originating from the small intestine may represent a player in eCBome-and/or gut mBIome-mediated effects on food intake and energy metabolism

Three of a Kind: Control of the Expression of Liver-Expressed Antimicrobial Peptide 2 (LEAP2) by the Endocannabinoidome and the Gut Microbiome

The endocannabinoidome (expanded endocannabinoid system, eCBome)-gut microbiome (mBIome) axis plays a fundamental role in the control of energy intake and processing. The liver-expressed antimicrobial peptide 2 (LEAP2) is a recently identified molecule acting as an antagonist of the ghrelin receptor and hence a potential effector of energy metabolism, also at the level of the gastrointestinal system. Here we investigated the role of the eCBome-gut mBIome axis in the control of the expression of LEAP2 in the liver and, particularly, the intestine. We confirm that the small intestine is a strong contributor to the circulating levels of LEAP2 in mice, and show that: (1) intestinal Leap2 expression is profoundly altered in the liver and small intestine of 13 week-old germ-free (GF) male mice, which also exhibit strong alterations in eCBome signaling; fecal microbiota transfer (FMT) from conventionally raised to GF mice completely restored normal Leap2 expression after 7 days from this procedure; in 13 week-old female GF mice no significant change was observed; (2) Leap2 expression in organoids prepared from the mouse duodenum is elevated by the endocannabinoid noladin ether, whereas in human Caco-2/15 epithelial intestinal cells it is elevated by PPARγ activation by rosiglitazone; (3) Leap2 expression is elevated in the ileum of mice with either high-fat diet—or genetic leptin signaling deficiency—(i.e., ob/ob and db/db mice) induced obesity. Based on these results, we propose that LEAP2 originating from the small intestine may represent a player in eCBome- and/or gut mBIome-mediated effects on food intake and energy metabolism

Three of a Kind: Control of the Expression of Liver-Expressed Antimicrobial Peptide 2 (LEAP2) by the Endocannabinoidome and the Gut Microbiome

The endocannabinoidome (expanded endocannabinoid system, eCBome)-gut microbiome (mBIome) axis plays a fundamental role in the control of energy intake and processing. The liver-expressed antimicrobial peptide 2 (LEAP2) is a recently identified molecule acting as an antagonist of the ghrelin receptor and hence a potential effector of energy metabolism, also at the level of the gastrointestinal system. Here we investigated the role of the eCBome-gut mBIome axis in the control of the expression of LEAP2 in the liver and, particularly, the intestine. We confirm that the small intestine is a strong contributor to the circulating levels of LEAP2 in mice, and show that: (1) intestinal Leap2 expression is profoundly altered in the liver and small intestine of 13 week-old germ-free (GF) male mice, which also exhibit strong alterations in eCBome signaling; fecal microbiota transfer (FMT) from conventionally raised to GF mice completely restored normal Leap2 expression after 7 days from this procedure; in 13 week-old female GF mice no significant change was observed; (2) Leap2 expression in organoids prepared from the mouse duodenum is elevated by the endocannabinoid noladin ether, whereas in human Caco-2/15 epithelial intestinal cells it is elevated by PPARγ activation by rosiglitazone; (3) Leap2 expression is elevated in the ileum of mice with either high-fat diet—or genetic leptin signaling deficiency—(i.e., ob/ob and db/db mice) induced obesity. Based on these results, we propose that LEAP2 originating from the small intestine may represent a player in eCBome- and/or gut mBIome-mediated effects on food intake and energy metabolism

Numerical study on the time evolutions of the electric field in helium plasma jets with positive and negative polarities

International audienceThis paper presents 2D simulations of atmospheric pressure discharges in helium with N2 and O2 admixtures, propagating in a dielectric tube between a point electrode and a grounded metallic target. For both positive and negative polarities, the propagation of the first ionization front is shown to correspond to a peak of the absolute value of the axial electric field inside the tube, but also outside the tube. After the impact on the metallic target, a rebound front is shown to propagate from the target to the point electrode. This rebound front is 23 times faster than the first ionization front. Close to the high voltage point, this rebound front corresponds to a second peak of the absolute value of the axial electric field. Close to the target, as the first ionization and rebound fronts are close in time, only one peak is observed. The dynamics of the absolute value of the radial component of electric field outside the tube is shown to present an increase during the first ionization front propagation and a fast decrease corresponding to the propagation of the rebound front. These time evolutions of the electric field components are in agreement with experiments. Finally, we have shown that the density of metastable He * in 99% He1% N2 and 99% He1% O2 atmospheric pressure discharges are very close. Close to the grounded target, the peak density of reactive species is significantly increased due to the synergy between the first ionization and rebound fronts, as observed in experiments. Similar results are obtained for both voltage polarities, but the peak density of metastable He* close to the target is shown to be two times less in negative polarity than in positive polarity

2D radial-azimuthal particle-in-cell benchmark for E × B discharges

International audienc

Investigation of a plasma–target interaction through electric field characterization examining surface and volume charge contributions: modeling and experiment

Numerical simulations and experiments are performed to better understand the interaction between a pulsed helium plasma jet and a dielectric target. The focus of this work lies on the volume and surface charge influence on the electric field distribution. Experimentally, the electric field due to surface charges is measured inside an electro-optic target under exposure of a plasma jet, using the optical technique called Mueller polarimetry. For the first time, the time-resolved spatial distributions of both the axial and radial components of electric field inside the target are obtained simultaneously. A 2D fluid model is used in a complementary way to the experiments in order to study separately the contribution of volume charges and surface charges to the spatio-temporal evolutions of the electric field during the plasma–surface interaction. The experimental investigation shows that the average axial and radial components of electric field inside the dielectric target, only due to surface charges, are lower than generally reported for electric field values in the plasma plume. Thanks to the phenomenological comparison with experiments, simulations show that during the plasma–surface interaction two effects sequentially determine the electric field inside the target: firstly, a relatively high electric field is observed due to the proximity of the ionization front; afterwards, in longer timescales, lower electric fields are induced due to the contribution of both leftover volume charges close to the target and surface charges deposited on its surface. The experimental technique provides a unique way to examine this second phase of the plasma–surface interaction