Effects of Bacterial CLPB Protein Fragments on Food Intake and PYY Secretion.

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague-Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.

Intestinal lymphatic alteration in mouse models of energy imbalance.

In obesity or anorexia, changes in body composition and mostly alterations in fat mass distribution are observed. The lymphatic system, which is implicated in fat absorption, might play a major role in the phenotype and development of these pathologies. In this study, two mice animal models were used: the high-fat diet model used for obesity and the activity-based anorexia model for anorexia. Lymphatic system marker levels were measured by reverse transcriptase quantitative polymerase chain reaction on the different parts of the intestine. Moreover, the effects of these models were evaluated on lymphatic fat absorption using lipidic tracer. Using these two models, lymphatic system alterations were observed. Indeed, whether in the obesity or the anorectic model, lymphatic fat absorption modifications were noticed with an increase of this parameter in the anorectic mice and a decrease in obesity. Expression levels of lymphatic markers also were impaired in these models. Both obesity and anorectic models induced lymphatic system alterations mainly in the jejunum and ileum parts of the intestine. These alterations are associated with lipid absorption modifications.

Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice-a new potential probiotic for appetite and body weight management.

BACKGROUND/OBJECTIVES: Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity. METHODS: The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alvei HA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/ob and high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the "MetaHIT" database. RESULTS: Chronic per os administration of native but not ClpB-deficient E.coli strain reduced body weight gain (p < 0.05) and daily meal frequency (p < 0.001) in ob/ob mice. Oral gavage of H.alvei for 18 and 46 days in ob/ob and HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p < 0.05) and decreased food intake in hyperphagic ob/ob mice (p < 0.001). Elevated fat tissue levels of phosphorylated hormone-sensitive lipase were detected in H.alvei -treated ob/ob mice (p < 0.01). Enterobacterial ClpB gene richness was lower in obese vs. non-obese humans (p < 0.0001) and correlated negatively with BMI in genera of Enterobacter, Klebsiella and Hafnia. CONCLUSIONS: H.alvei HA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alvei as a probiotic for appetite and body weight management in overweight and obesity.

Hafnia alvei HA4597 Strain Reduces Food Intake and Body Weight Gain and Improves Body Composition, Glucose, and Lipid Metabolism in a Mouse Model of Hyperphagic Obesity.

Use of new generation probiotics may become an integral part of the prevention and treatment strategies of obesity. The aim of the present study was to test the efficacy of a potential probiotic strain of lactic bacteria Hafnia alvei (H. alvei) HA4597™, in a mouse model of obesity characterized by both hyperphagia and diet-induced adiposity. For this purpose, 10-week-old high-fat-diet (HFD)-fed hyperphagic ob/ob male mice received a daily treatment with 1.4 × 1010 CFU of H. alvei for 38 days. Effects of H. alvei were compared to those of a lipase inhibitor orlistat (80 mg/kg daily) and a vehicle (NaCl 0.9%) in HFD-fed ob/ob mice. A control untreated group of ob/ob mice received the standard diet throughout the experiment. The vehicle-treated HFD group displayed increased food intake, worsening of adiposity, and glycemia. Treatment with H. alvei was accompanied by decreased body weight and fat-mass gain along with reduced food intake to the level of the standard-diet-fed mice. At the end of the experiment, the group treated with H. alvei showed a decrease of glycemia, plasma total cholesterol, and alanine aminotransferase. The orlistat-treated mice showed a lower rate of body weight gain but were hyperphagic and hyperglycemic. These results demonstrate the beneficial anti-obesity and metabolic effects of H. alvei HA4597™ in mice with obesity resulting from hyperphagia and diet-induced adiposity.

Changes in Microbiota and Bacterial Protein Caseinolytic Peptidase B During Food Restriction in Mice: Relevance for the Onset and Perpetuation of Anorexia Nervosa.

Microbiota contributes to the regulation of eating behavior and might be implicated in the pathophysiology of anorexia nervosa. ClpB (Caseinolytic peptidase B) protein produced mainly by the Enterobacteriaceae family has been identified as a conformational mimetic of α-MSH, which could result in similar anorexigenic effects. The aim of this study was to highlight the role of the microbiome and the ClpB protein in deregulation and self-maintenance of anorexia pathology. Male C57Bl/6 mice were undergone to the ABA (Activity-Based Anorexia) protocol: after 5 days of acclimatization, both ABA and LFA (Limited Food Access) mice had progressively limited access to food until D17. At the end of protocol, the plasma ClpB concentration and Enterobacteriaceae DNA in colonic content were measured. As expected, dietary restriction induced lost weight in LFA and ABA mice. At D10, colonic permeability and plasma concentration of the ClpB protein were significantly increased in LFA and ABA mice vs. controls. At D17, plasma concentration of ClpB was increased in LFA and ABA mice and, it was correlated with proportion of Enterobacteriaceae in the faeces. These abnormally high ClpB concentrations and all associated factors, and therefore might contribute to the initiation and/or perpetuation of anorexia nervosa by interfering with satiety signaling.

Manía y bebidas energéticas / Mania and energy drinks

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Trastornos neuropsiquiátricos en un caso de lesión cerebral por carabina de aire comprimido / Neuropsychiatric disorders in a case of a brain injury due to an air gun shot

Las secuelas neuropsiquiátricas tras un traumatismo craneoencefálico (TCE) pueden ser muy variadas e incluso aparecer años después del mismo. Se han descrito síndromes diversos que producen un grado variable de discapacidad y descenso en la calidad de vida percibida de pacientes y familiares, y que pueden presentar dificultades diagnósticas y de manejo terapéutico. Así, se registran en la literatura médica cambios en los rasgos de personalidad premórbidos, en el humor y en la afectividad, ansiedad, estrés postraumático, trastornos psicóticos y disfunción cognitiva, entre otros. Síntomas como la escasa motivación, la falta de interés por el entorno y el déficit ideoverbal y afectivo son atribuibles a varios de estos síndromes. Se presenta el caso de un varón de 38 años de edad, previamente diagnosticado de trastorno disocial de la personalidad que, tras intento autolítico por disparo con carabina de aire comprimido, sufre un traumatismo frontoparietal con un absceso cerebral posterior. Durante su evolución presentó de manera sucesiva distintas complicaciones y secuelas neuropsiquiátricas del TCE, observándose modificación de sus rasgos caracteriales previos, trastorno psicótico postraumático y finalmente deterioro cognitivo (AU)

Neuropsychiatric consequences after traumatic brain injury can appear in many forms, even years after the event. Several syndromes have been described that lead to disability and a decrease in the quality of life to a varying degree of patients and relatives. These can be difficult to diagnosis and treat. In fact, there are records in literature of changes in premorbid personality traits including, mood and affectivity, anxiety, post-traumatic stress, psychotic disorders, and cognitive dysfunction. Symptoms like low motivation, lack of interest in surroundings and idea-verbal and affective lack are attributable to some of these syndromes. We present the clinical case of a 38 year old man previously diagnosed with antisocial personality disorder who, after attempted suicide by an air gun shot, suffered frontoparietal trauma with subsequent brain abscess. During his evolution he had different complications and neuropsychiatric consequences of traumatic brain injury. Changes could be observed in previous personality traits, post-traumatic psychotic disorder, and finally cognitive impairment (AU)