Charles-Henri Malbert

French National Institute for Agriculture, Food, and Environment (INRAE) | INRAE · Dept of human nutrition

Background & Aims Severe malnutrition exposes patients to adverse outcomes and a higher mortality risk. The Yucatan minipig, closer to human physiology than murine models could be a pertinent and innovative experimental model for studying the physiopathology and consequences of severe malnutrition. The present study aimed to determine whether a low...

Background Here we present an open-source solution, comprising several 3D-printable mechanical pieces and software tools, for frameless stereotaxic targeting in young and adult pigs of varying weights. New method Localization was achieved using an IR camera and CT imaging. The positions of the tools were followed, after registration of the pig ste...

Signals arising from the upper part of the gut are essential for the regulation of food intake, particularly satiation. This information is supplied to the brain partly by vagal nervous afferents. The porcine model, because of its sizeable gyrencephalic brain, omnivorous regimen, and comparative anatomy of the proximal part of the gut to that of hu...

Introduction N3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects for the hypothalamus, but their extra-hypothalamic outcome lack documentation. We evaluated the central consequences of the substitution of saturated fatty acids with n-3 or n-6 PUFA in obesogenic diets. Methods Twenty-one miniature pigs were fed ad libitum obe...

Background Uterine transplant (UT) represents an opportunity to treat absolute uterine infertility. However, the use of uterine veins for venous return, in addition to ovarian veins, significantly increases the risk of ureteral wounds in the living donor and UT time for the recipient. Our aim was to demonstrate that dual ovarian venous return is su...

Context Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent ADA guidelines have sub-categorized ‘non-severe’ hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulat...

Palatable sweet/fatty foods overconsumption is a major risk factor for obesity and eating disorders, also having an impact on neuro-behavioural hedonic and cognitive components comparable to what is described for substance abuse. We hypothesized that Yucatan minipigs would show hedonic, cognitive, and affective neuro-behavioral shifts when subjecte...

Introduction The insulinotropic capacity of exogenous glucagon like peptide-1 (GLP-1) is reduced in type 2 diabetes and the insulin-resistant obese. We have tested the hypothesis that this response is the consequence of a reduced pancreatic GLP-1 receptor (GLP-1r) density in insulin-resistant obese animals. Research design and methods GLP-1r densi...

The glucose portal sensor informs the brain of changes in glucose inflow through vagal afferents that require an activated glucagon-like peptide 1 receptor (GLP-1r). The GLP-1 system is known to be impaired in insulin-resistant conditions, and we sought to understand the consequences of GLP-1 resistance on glucose portal signaling. GLP-1-dependent...

Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 hea...

Aims: To evaluate the effects of 8 weeks' administration of exenatide once-weekly (ExQW) on gastric emptying of solids and liquids (using the 'gold standard' technique, scintigraphy), glucose absorption and postprandial glycaemia in health. Material and methods: Thirty two healthy participants were randomized to receive ExQW (2mg per week subcut...

Aims: Gastric emptying is a major determinant of postprandial glycaemia in both health and type 2 diabetes (T2DM); the potential impact of ethnicity on gastric emptying is unclear. We compared the rate of gastric emptying of a standardised meal and the associated glycaemic response in Han Chinese and Caucasian patients with T2DM. Methods: 14 Han...

Purposes Whether low-calorie sweeteners (LCS), such as sucralose and acesulfame K, can alter glucose metabolism is uncertain, particularly given the inconsistent observations relating to insulin resistance in recent human trials. We hypothesized that these discrepancies are accounted for by the surrogate tools used to evaluate insulin resistance an...

Psychological chronic stress is associated with the development of mood disorders, and spices have shown protective properties in this context. This research investigated the effects of a supplementation with a functional food ingredient containing spice extracts in a pig model of psychosocial chronic stress. Its impact on behavior, neurophysiology...

Background/objective: Changes in brain metabolism has been investigated thoroughly during unilateral cervical chronic vagal stimulation in epileptic or depressive patients. Bilateral stimulation of the abdominal vagus (aVNS) has received less attention despite the reduction in body weight and an altered feeding behavior in obese animals that could...

Background: In the context of morbid obesity, vagus nerve stimulation could be used to control gastric function targeting the small afferent B-fibers and C-fibers. Compared to large A-fibers, activation thresholds of these small efferent fibers are 10 to 100 times greater, inducing technical constraints and possible nerve damages. Although rectang...

Gastric emptying of food is mainly driven by the caloric concentration, the rheological properties of the chyme, and the physical state (liquid/solid) of food once in the stomach. The present work investigated: (1) The effect of the composition and the viscosity of drinkable yogurts on gastric emptying in pigs, and (2) the behavior of yogurts durin...

Objective: This study evaluated gastric emptying (GE) and small intestinal (SI) transit in people with morbid obesity and their relationships to glycaemia, incretin hormones, and glucose absorption METHODS: GE and caecal arrival time (CAT) of a mixed meal were assessed in 22 morbidly obese (50.2 ± 2.5 years; 13 F:9 M; BMI: 48.6 ± 1.8 kg/m2) and 10...

This study explores the long-term effects of exposure to a maternal Western diet (WD) vs. standard diet (SD) in the Yucatan minipig, on the adult progeny at lean status ( n = 32), and then overweight status. We investigated eating behavior, cognitive abilities, brain basal glucose metabolism, dopamine transporter availability, microbiota activity,...

Objective There is a general agreement that there are changes in brain metabolism in insulin‐resistant individuals during conditions of hyperinsulinemia. However, the impact on obesity is unclear, and the metabolic constants underlying these modifications are unknown. The aim of this study was to evaluate these changes in a large animal model of di...

Miniature pig as a model for translational therapy – Vagal stimulation and metabolic syndrome Therapeutic innovation against morbid obesity requires alternate animal models such as the diet induced obese miniature pig. While it does not develop the panel of diseases associated with obesity such as diabetes, atherosclerosis and metabolic syndrome,...

Butyrate can improve gut functions, whereas histone deacetylase inhibitors might alleviate neurocognitive alterations. Our aim was to assess whether oral butyrate could modulate brain metabolism and plasticity and if this would relate to gut function. Sixteen pigs were subjected to sodium butyrate (SB) supplementation via beverage water or water on...

Background: Abdominal bilateral vagal stimulation reduces food intake in animals. However, the classical square wave, mA range current generator is poorly effective to evoke action potentials on A∂ and C neurons that represent the majority of vagal neurons at the abdominal level. Objective/hypothesis: METHODS: The current thresholds for pulsons...

Acute vagal stimulation modifies glucose and insulin metabolism, but the effect of chronic bilateral vagal stimulation is not known. Our aim was to quantify the changes in whole body and organ-specific insulin sensitivities, 12 weeks after permanent, bilateral, vagal stimulation performed at the abdominal level in adult mini-pigs. In 15 adult mini-...

Acute vagal stimulation modifies glucose and insulin metabolism, but the effect of chronic bilateral vagal stimulation is not known. Our aim was to quantify the changes in whole body and organ-specific insulin sensitivities, 12 weeks after permanent, bilateral, vagal stimulation performed at the abdominal level in adult mini-pigs. In 15 adult mini-...

Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their c...

Objective: Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. Approach: This review examines the state of t...

Obesity-associated alterations of glucose metabolism are ameliorated after chronic stimulation of abdominal vagus nerve

Vagal nerve activity has been shown to be impacted in the case of Heart Failure. A direct recording of vagal nerve activity could be useful to investigate its characteristics, especially in the case of the vagal nerve stimulation therapy, which has been shown to be useful in heart failure patients. The objective of this paper is to validate the mea...

This paper describes the fabrication and the packaging of a flexible parylene-based multi-contact electrode embedded in a silicone-based cuff. This type of electrode is well suited for peripheral nerve recording and offers improved spatial selectivity. We conducted mechanical and electrical tests for assessing the reliability by using an accelerate...

The voltage required to stimulate small diameter myelinated (Adelta fibres) and unmyelinated (C fibres) neurons consistently is so large that it is unsafe for chronic vagal stimulation. We present here a solution that reduces by 80% the amount of electrical charge necessary to produce action potential. These solutions were tested in a porcine model...

This paper investigates the simultaneous use of two separate multicontact cuff (MCC) electrodes for selective recordings in electroneurography (ENG) and peripheral nerve selective stimulation.Multicontact VNS yields the appealing idea that one could perform selective VNS by using adapted spatio-temporal patterns and thus minimize side effects. In h...

Vagal nerve activity has been shown to be impacted in the case of Heart Failure. A direct recording of vagal nerve activity could be useful to investigate its characteristics, especially in the case of the vagal nerve stimulation therapy, which has been shown to be useful in heart failure patients. The objective of this paper is to validate the mea...

The voltage required to stimulate small diameter myelinated (Adelta fibres) and unmyelinated (C fibres) neurons consistently is so large that it is unsafe for chronic vagal stimulation. We present here a solution that reduces by 80% the amount of electrical charge necessary to produce action potential. These solutions were tested in a porcine model...

This paper describes the fabrication and the packaging of a flexible parylene-based multi-contact electrode embedded in a silicone-based cuff. This type of electrode is well suited for peripheral nerve recording and offers improved spatial selectivity. We conducted mechanical and electrical tests for assessing the reliability by using an accelerate...

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in...

The purpose of this paper is to present a methodology for characterizing the rheological properties of heterogeneous gastric contents, for the first time, to our knowledge. Pigs were used as a model because their gastric system is similar to that of humans. Bread was chosen as a high-calorific, solid test meal. The bread was made with flours offeri...

Introduction et but de l’étude: La caractérisation des réseaux cérébraux impliqués dans le traitement des signaux sucrés gustatifs et/ou viscéraux chez un modèle animal pertinent en nutrition humaine pourrait aider à mieux comprendre les mécanismes centraux liés au contrôle de l’ingestion et les causes potentielles de certains troubles du comportem...

Objective The pandemic of obesity in Western countries is mainly due to the high-fat, high-energy diet prevailing there. Obesity-associated metabolic disorders are the consequence of fat mass increase leading to altered adipokine secretion, hyperlipemia, oxidant stress, low-grade inflammation, and eventually glucose intolerance. Yet not all people...

Background Substantial increases in dietary sugar intake together with the increasing prevalence of obesity worldwide, as well as the parallels found between sugar overconsumption and drug abuse, have motivated research on the adverse effects of sugars on health and eating behaviour. Given that the gut–brain axis depends on multiple interactions be...

The characterization of brain networks contributing to the processing of oral and/or intestinal sugar signals in a relevant animal model might help to understand the neural mechanisms related to the control of food intake in humans and suggest potential causes for impaired eating behaviors. This study aimed at comparing the brain responses triggere...

Nutrient-sensing studies in humans frequently use intragastric intubation. A non-invasive alternative would be the use of freeze-dried lipids (FDL) capsules. We proposed to validate this method in pigs by (i) demonstrating that low-dose FDL can increase vagal activity, gastric compliance (GC), and delay gastric emptying time (GET); (ii) evaluating...

The pig, which shares several similarities with humans, is increasingly used for biomedical research, particularly in nutrition and neurosciences. Recent studies in minipigs have shown that a deleterious nutritional environment (e.g. a high-fat and high-sugar diet) induces obesity which, as in humans, is associated with increased adiposity, insulin...

Introduction et but de l’étude: La consommation chronique de régimes riches en matières grasses favorise l’inflammation à bas bruit conduisant aux maladies métaboliques et à l’obésité. Le passage anormalement élevé de composés pro-inflammatoires bactériens (CBPI ; e.g. lipopolysaccharide, LPS), du tube digestif vers le milieu intérieur, serait pour...

This study investigated the behavioural and brain responses towards conditioned flavours with different hedonic values in juvenile pigs. Twelve 30-kg pigs were given four three-day conditioning sessions: they received three different flavoured meals paired with intraduodenal (i.d.) infusions of 15% glucose (F(Glu)), lithium chloride (F(LiCl)), or s...

Proximal gastric vagotomy (PGV) has little impact on the normal pattern of solid gastric emptying, despite denervation of the proximal two thirds of the stomach and loss of the proximal gastric pump. In four healthy volunteers and four patients with PGV, we investigated the possible compensatory mechanisms that may come into play after proximal den...

Peripheral and central glucose sensing play a major role in the regulation of food intake. Peripheral sensing occurs at duodenal and portal levels, although the importance of these sensing sites is still controversial. The present study aimed to compare the respective influence of these sensing pathways on the eating patterns; plasma concentrations...

Gizzard motility was compared between chickens from D(+) (high digestion efficiency) and D(-) (low digestion efficiency) genetic lines selected for divergent digestion efficiency, using strain gauge transducers. Motility was recorded continuously during 24 h in 6 birds per line. Two stimuli, a meal distribution after a feed-deprivation period and l...

We describe the behavioural consequences of conditioned flavour aversion and preference in pigs and have investigated the brain circuits involved in the representation of flavours with different hedonic values. The study was performed on eight 30-kg pigs. (i) Animals were negatively conditioned to an F- flavour added to a meal followed by LiCl intr...

Compared to lean subjects, obese men have less activation in the dorsolateral prefrontal cortex, a brain area implicated in the inhibition of inappropriate behavior, satiety, and meal termination. Whether this deficit precedes weight gain or is an acquired feature of obesity remains unknown. An adult animal model of obesity may provide insight to t...

Alterations in ileal and colonic permeability by chronic intake of high-lipid diets enriched with omega 3, omega 6 or saturated fat - Volume 70 Issue OCE6 - J. P. Lallès, C. Perrier, D. Val-Laillet, C. H. Malbert

Central functions altered by chronic high-lipids diets enriched with omega 3, omega 6 or saturated fat - Volume 70 Issue OCE6 - D. Val-Laillet, P. Meurice, J. P. Lallès, C. H. Malbert

The aim of the present study was to describe and validate a computed tomography (CT) method to analyse adiposity distribution in Göttingen minipigs. Adiposity was evaluated in two groups of minipigs. In group 1 (n 8), measurements were performed before and after the induction of obesity. In group 2 (n 7), animals were fed rations designed to obtain...

The aim of our study was to investigate whether the altered eating behavior observed in the context of a diet-induced metabolic syndrome is related to changes of the gastric emptying and autonomic balance. Eight adult male Göttingen minipigs were subjected during 5months to ad libitum Western diet (WD). Several factors were compared between the lea...

Chronic vagus nerve stimulation (VNS) is known to influence food intake and body weight in animals and humans. The aim of our work was to evaluate the effects of long-term VNS in adult obese minipigs. Eight minipigs were fed ad libitum a Western diet to cause obesity, after which half of the animals were implanted with bilateral vagal electrodes co...

We used high-magnetic field (4.7 T) magnetic resonance imaging (MRI) to build the first high-resolution (100 microm x 150 microm x 100 microm) three-dimensional (3D) digital atlas in stereotaxic coordinates of the brain of a female domestic pig (Sus scrofa domesticus). This atlas was constructed from one hemisphere which underwent a symmetrical tra...

The entero-pancreatic (EP) neurons directly link the proximal duodenum to the pancreas and participate to the pre absorptive phase of postprandial insulin secretion. EP neurons may therefore play a critical role in the postprandial inhibition of hepatic gluconeogenesis mandatory for an adequate postprandial glucose tolerance and a good overall insu...

The intragastric balloon, filled with air or liquid is used before elective bariatric surgery because its efficacy is limited. This might be the consequence of altered gastric functions. Therefore, we aimed to investigate, in an animal model, the changes in gastric motility and emptying induced by long-term insertion of a balloon used for weight re...