LRP1 Receptor Controls Adipogenesis and Is Up-Regulated In Human and Mouse Obese Adipose Tissue

The cell surface low-density lipoprotein receptor-related protein 1, LRP1, plays a major role in lipid metabolism. The question that remains open concerns the function of LRP1 in adipogenesis. Here, we show that LRP1 is highly expressed in murine preadipocytes as well as in primary culture of human adipocytes. Moreover, LRP1 remains abundantly synthesised during mouse and human adipocyte differentiation. We demonstrate that LRP1 silencing in 3T3F442A murine preadipocytes significantly inhibits the expression of PPARγ, HSL and aP2 adipocyte differentiation markers after adipogenesis induction, and leads to lipid-depleted cells. We further show that the absence of lipids in LRP1-silenced preadipocytes is not caused by lipolysis induction. In addition, we provide the first evidences that LRP1 is significantly up-regulated in obese C57BI6/J mouse adipocytes and obese human adipose tissues. Interestingly, silencing of LRP1 in fully-differentiated adipocytes also reduces cellular lipid level and is associated with an increase of basal lipolysis. However, the ability of mature adipocytes to induce lipolysis is independent of LRP1 expression. Altogether, our findings highlight the dual role of LRP1 in the control of adipogenesis and lipid homeostasis, and suggest that LRP1 may be an important therapeutic target in obesity

Résistance à l'action des catécholamines, de la leptine et de l'insuline au cours de l'obésité : étude de la réactivité du système nerveux autonome "in vivo" et de la lipolyse "in vitro"

A decreased sympathetic nervous system (SNS) reactivity could be involved in the physiopathology of obesity. We used spectral analysis to measure the variability of heart rate and blood pressure in normotensive obese subjects. In standing position, baroreflexe sensitivity and SNS reactivity were altered and negatively correlated to insulin resistance indexes. After a glucose load, an impaired change in indices of sympathetic modulation was observed. Increased leptin to fat mass ratio was paradoxically associated with a decreased sympathetic cardiac modulation. This relationship persisted after weight loss. These abnormalities including impaired SNS reactivity, insulin resistance and an increased leptin concentration for a given fat mass, without hypertension could be described as a particular phenotype of obesity. Catecholamine resistance of adipocyte lipolysis could be related to cell membrane abnormalities. This hypothesis was tested in vitro by increasing the membrane sphingomyelin content of 3T3L1 adipocytes. At short term, a decrease in stimulated lipolysis was observed, that could be related to abnormal membrane signal transduction. The transcription of genes implicated in the regulation of cholesterol metabolism and lipogenesis was activated, but without change in the transcription of beta-adrenergic receptors.Une diminution de la réponse du système nerveux sympathique (SNS) pourraient être impliquée dans la physiopathologie de l'obésité. Nous avons étudié la variabilité de la fréquence cardiaque et de la tension artérielle chez des sujets obèses normotendus. La réactivité du SNS en orthostatisme et la sensibilité du baroréflexe étaient altérées et corrélées de façon indépendante au degré d'insulinorésistance. Les variations de la réponse du SNS lors d'une charge en glucose, rapportée aux variations d'insulinémie, étaient plus faibles au cours de l'obésité. Une concentration élevée en leptine était paradoxalement associée à une diminution des indices du SNS. Cette relation persiste après amaigrissement. Ces études ont donc permis de décrire un phénotype d'obésité associant une diminution globale de la réactivité du système sympathique, une augmentation du rapport leptine sur masse grasse, une insulino-résistance et une absence d'hypertension artérielle. Ce phénotype est associé à une augmentation de la sphingomyéline membranaire de l'erythrocyte. Un modèle de résistance aux catécholamines de la lipolyse adipocytaire a été validé in vitro en enrichissant en sphingomyéline les membranes d'adipocytes 3T3L1 en culture. La diminution de lipolyse était en rapport avec une altération de l'étape membranaire de la transmission du signal. La transcription de nombreux gènes impliqués dans la régulation du métabolisme du cholestérol et de la lipogenèse a été activé, sans modification de l'expression des récepteurs bêta-adrénergiques

Formative assessment in clinical nutrition: Parenteral nutrition in hospitalised adult

Group Authors : Soc Francophone Nutr Clinique hospitalised adultNational audienc

To the editor

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Dysmagnesemia in Covid-19 cohort patients: prevalence and associated factors

International audienceHypomagnesemia and hypermagnesemia could have serious implications and possibly lead to progress from a mild form to a severe outcome of Covid-19. Susceptibility of subjects with low magnesium status to develop and enhance this infection is possible. There is little data on the magnesium status of patients with Covid-19 with different degrees of severity. This study was conducted to evaluate prevalence of dysmagnesemia in a prospective Covid-19 cohort study according to the severity of the clinical manifestations and to identify factors associated.Serum magnesium was measured in 300 of 549 patients admitted to the hospital due to severe Covid-19. According to the WHO guidelines, patients were classified as moderate, severe, or critical. 48% patients had a magnesemia below 0.75 mmol/L (defined as magnesium deficiency) including 13% with a marked hypomagnesemia (<0.65 mmol/L). 9.6% had values equal to or higher than 0.95 mmol/L. Serum magnesium concentrations were significantly lower in female than in male (0.73 +/- 0.12 vs 0.80 +/- 0.13 mmol/L), whereas the sex ratio M/F was higher in severe and critical form (p<0.001). In a bivariate analysis, the risk of magnesium deficiency was significantly and negatively associated with infection severity (p<0.001), sex ratio (M/F, p<0.001), oxygenotherapy (p<0.001), stay in critical care unit (p=0.028), and positively with nephropathy (p=0.026). Logistic regression analysis revealed that the strongest predictors of magnesium deficiency were female sex (OR=2.67, p<0.001) and nephropathy (OR=2.12, p=0.032) and after exclusion of sex ratio, the severity of infection (OR=0.46, p=0.04 and OR=0.39 p=0.01), for critical and moderate forms, respectively. This transversal study reveals a high prevalence of hypomagnesemia in hospitalized patients for Covid-19, while high-level serum magnesium concentration was more prevalent in critical form

Nutrition entérale à domicile en site jéjunal [Home enteral nutrition by the jejunal route]

La nutrition en site jéjunal s’est encore développée, particulièrement lors de troubles de la déglutition, de reflux gastro-œsophagien et d’obstacle sur le tube digestif haut. L’accès au jéjunum n’est plus réservé à la chirurgie mais peut reposer aujourd’hui sur les techniques de pose de sonde et de stomie par voie endoscopique et radiologique. Ce cas clinique concernant un patient ayant fait un accident vasculaire cérébral permet de faire le point sur ces nouvelles techniques de jéjunostomie et gastrojéjunostomie. Elles se révèlent précieuses pour la nutrition à domicile car elles limitent le recours à une laparotomie ou laparoscopie, voire à une nutrition parentérale. [Jejunal nutrition has developed nowadays, especially for patients with swallowing disorders, severe gastro-oesophageal reflux disease or previous history of aspiration pneumonia, and obstruction of the upper GI tract. Access to the jejunum is no longer restricted to surgery thanks to the development of tube feeding insertions radiological and endoscopic techniques. This clinical case of a stroke patient underlines the clinical indications of these recent radiology or endoscopy-guided jejunostomies and gastrojejunostomies. They are suitable for home nutrition support as they could avoid surgical laparotomy or laparoscopy or even, parenteral nutrition.]]]> Internal Medicine; Nutrition and Dietetics; Endocrinology, Diabetes and Metabolism fre oai:serval.unil.ch:BIB_FB02A9DAD33D 2022-05-07T01:30:36Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_FB02A9DAD33D Recommendations for the use of multimodal monitoring in the neurointensive care unit. info:doi:10.1097/MCC.0000000000000179 info:eu-repo/semantics/altIdentifier/doi/10.1097/MCC.0000000000000179 info:eu-repo/semantics/altIdentifier/pmid/25689123 Citerio, G. Oddo, M. Taccone, F.S. info:eu-repo/semantics/review article 2015 Current Opinion in Critical Care, vol. 21, no. 2, pp. 113-119 info:eu-repo/semantics/altIdentifier/eissn/1531-7072 urn:issn:1070-5295 <![CDATA[PURPOSE OF REVIEW: Multimodal monitoring (MMM) is routinely applied in neurointensive care. Unfortunately, there is no robust evidence on which MMM-derived physiologic variables are the most clinically relevant, how and when they should be monitored, and whether MMM impacts outcome. The complexity is even higher because once the data are continuously collected, interpretation and integration of these complex physiologic events into targeted individualized care is still embryonic. RECENT FINDINGS: Recent clinical investigation mainly focused on intracranial pressure, perfusion of the brain, and oxygen availability along with electrophysiology. Moreover, a series of articles reviewing the available evidence on all the MMM tools, giving practical recommendations for bedside MMM, has been published, along with other consensus documents on the role of neuromonitoring and electroencephalography in this setting. SUMMARY: MMM allows comprehensive exploration of the complex pathophysiology of acute brain damage and, depending on the different configuration of the pathological condition we are treating, the application of targeted individualized care. Unfortunately, we still lack robust evidence on how to better integrate MMM-derived information at the bedside to improve patient management. Advanced informatics is promising and may provide us a supportive tool to interpret physiologic events and guide pathophysiological-based therapeutic decisions

Référentiel de pratiques professionnelles: soins et surveillance des accès veineux centraux de l'adulte pour la nutrition parentérale [Formative assessment in clinical nutrition: Care management of parenteral nutrition central venous access]

Les voies veineuses centrales (VVC) sont essentielles pour l'administration de la nutrition parentérale. Le risque de complications est dépendant de la qualité des soins apportés à la VVC qui influence de ce fait la qualité de vie des patients et le coût des soins. Beaucoup de complications des VVC, infectieuses ou non, peuvent être prévenues par l'existence de protocoles de soins appropriés et standardisés. L'information sur les soins des VVC et les éventuelles complications est essentielle pour le dépistage et le traitement précoce de ces complications ; elle doit faire l'objet de protocoles partagés entre les patients et les soignants. Cet article décrit une évaluation des pratiques professionnelles sous la forme d'un audit clinique destiné à améliorer la qualité de soins des patients en nutrition parentérale porteurs de VVC. Central venous access devices (CVAD) are essential for the administration of parenteral nutrition. The quality of the care of CVAD influences the risk of complications and so the quality of life of the patients and the costs of care. Numerous infectious or non-infectious complications of CVAD can be prevented by appropriate, standardized protocols of care. Information about the care of CVAD and complications is essential for the early recognition and treatment of complications and should be shared between patients and caregivers. This article describes an audit for CAVD care that can be used to improve quality of care in a professional practice evaluation program

Prise en charge nutritionnelle d'une ascite chyleuse [Nutritional management of chylous ascitis]

L’ascite chyleuse est une cause rare d’ascite. La majorité du temps, elle résulte de la lésion d’un canal lymphatique lors d’une chirurgie digestive ou uro-génitale, plus rarement elle est la conséquence d’un obstacle au drainage du flux lymphatique (processus néoplasique). Les conséquences nutritionnelles sont graves et conditionnent le pronostic évolutif. La dénutrition est liée à l’obligation d’exclure les acides gras alimentaires pour freiner la lymphorrhée. Le diagnostic repose sur le contexte et sur l’analyse cytologique et biochimique du liquide d’ascite. Le traitement lie intimement la prise en charge de l’état nutritionnel et de la cause sous-jacente. Le recours à une alimentation orale ou à une nutrition entérale pauvre en triglycérides à chaînes longues et enrichie en triglycérides à chaînes moyennes est une option thérapeutique majeure de l’ascite chyleuse. [Chylous ascitis is a rare cause of ascitis. Most of the time, it results of retroperitoneal lymph node or duct dissection during abdominal or urological surgery; it is rarely due to lymphatic obstruction (neoplasia). Nutritional damage is major and severely impairs prognosis. Malnutrition is due to the necessity to avoid fatty acid in meal to reduce chylous leakage. Diagnosis is based on patient's clinical history and cytologic and biochemical ascitis analyses. Treatment combines the correction of nutritional status and therapy of the causative disease. Oral diet or enteral nutrition with low content of long chain triglyceride, thus enriched in medium chain triglyceride, is the major therapeutic option of chylous ascitis.]]]> Internal Medicine; Nutrition and Dietetics; Endocrinology, Diabetes and Metabolism fre oai:serval.unil.ch:BIB_EC75ED6B6D14 2022-05-07T01:29:32Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_EC75ED6B6D14 Un Cingria de plein air Maggetti, Daniel Bergé, Aline info:eu-repo/semantics/article article 2020-09-28 Littérature, no. 199, pp. 5-8 info:eu-repo/semantics/altIdentifier/isbn/978-2-200-93308-1 <![CDATA[Introduction à un dossier «Charles-Albert Cingria» coordonné par Daniel Maggetti et Aline Berg

Inhibition of the RhoGTPase Cdc42 by ML141 enhances hepatocyte differentiation from human adipose-derived mesenchymal stem cells via the Wnt5a/PI3K/miR-122 pathway: impact of the age of the donor

Abstract Background Human adipose-derived mesenchymal stem cells (hADSCs) are promising cells that may promote hepatocyte differentiation (Hep-Dif) and improve liver function, but the involvement of Cdc42, a key small RhoGTPase which plays a crucial role in aging, is still not well established. We hypothesized that the inhibition of Cdc42 may rescue the hepatogenic potential of hADSCs derived from aged donors. Methods hADSCs isolated from 61 women of different ages were cultured for evaluation of the proliferation of cells, adherence, apoptosis, immunomodulation, immunophenotyping, multipotency, gene expression, and cell function during Hep-Dif. Inhibition of Cdc42 by ML141 was realized during two phases: initiation (days –2 to 14 (D–2/14)) from undifferentiated to hepatoblast-like cells, or maturation (days 14 to 28 (D14/28)) from undifferentiated to hepatocyte-like cells. Mechanistic insights of the Wnt(s)/MAPK/PI3K/miR-122 pathways were studied. Results Cdc42 activity in undifferentiated hADSCs showed an age-dependent significant increase in Cdc42-GTP correlated to a decrease in Cdc42GAP; the low potentials of cell proliferation, doubling, adherence, and immunomodulatory ability (proinflammatory over anti-inflammatory) contrary to the apoptotic index of the aged group were significantly reversed by ML141. Aged donor cells showed a decreased potential for Hep-Dif which was rescued by ML141 treatment, giving rise to mature and functional hepatocyte-like cells as assessed by hepatic gene expression, cytochrome activity, urea and albumin production, low-density lipoprotein (LDL) uptake, and glycogen storage. ML141-induced Hep-Dif showed an improvement in mesenchymal-epithelial transition, a switch from Wtn-3a/β-catenin to Wnt5a signaling, involvement of PI3K/PKB but not the MAPK (ERK/JNK/p38) pathway, induction of miR-122 expression, reinforcing the exosomes release and the production of albumin, and epigenetic changes. Inhibition of PI3K and miR-122 abolished completely the effects of ML141 indicating that inhibition of Cdc42 promotes the Hep-Dif through a Wnt5a/PI3K/miR-122/HNF4α/albumin/E-cadherin-positive action. The ML141(D–2/14) protocol had more pronounced effects when compared with ML141(D14/28); inhibition of DNA methylation in combination with ML141(D–2/14) showed more efficacy in rescuing the Hep-Dif of aged hADSCs. In addition to Hep-Dif, the multipotency of aged hADSC-treated ML141 was observed by rescuing the adipocyte and neural differentiation by inducing PPARγ/FABP4 and NeuN/O4 but inhibiting Pref-1 and GFAP, respectively. Conclusion ML141 has the potential to reverse the age-related aberrations in aged stem cells and promotes their hepatogenic differentiation. Selective inhibition of Cdc42 could be a potential target of drug therapy for aging and may give new insights on the improvement of Hep-Dif