Lack of “immunological fitness” during fasting in metabolically challenged animals
Notice bibliographique
Résumé
Obesity is associated with infi ltration of proinfl ammatory macrophages in adipose tissue and with a low-grade state of infl ammation as judged by systemic and tissue measurements of proinfl ammatory cytokines and acute-phase reactants ( 1 ). Numerous studies indicate that increased levels of free FAs (FFAs) are critical for the pathogenesis of the metabolic syndrome ( 2 ). For instance, palmitate can get channeled into increased biosynthesis of ceramides, which can cause insulin resistance, infl ammation, and apoptosis ( 3-5 ). Furthermore, intermediates of FFAs, through their conversion to triglycerides (lysophosphatidic acid, phosphatidic acid and diacylglycerol), can activate proinfl ammatory kinases ( 6 ). FFAs may also enhance infl ammation through binding and signaling through Toll-like receptor-4 (TLR4) ( 7 ). Thus, failure of adipose tissue to expand and/ or buffer excess FFAs may be the starting point for obesityand lipodystrophy-related metabolic disturbances. In obesity, as well as in critically ill patients, FFAs are chronically elevated and can induce a vicious proinfl ammatory cycle over the course of which adipocytes and macrophages further aggravate local and systemic infl ammation ( 8 ). In support of this hypothesis, intensive insulin treatment that inhibits lipolysis and hyperglycemia has been successful in the reduction of infl ammation and, more importantly, mortality of critically ill patients ( 9 ). In healthy individuals, lipolysis is effi ciently suppressed by insulin in the fed state. However, recent studies by Kosteli et al. ( This is also consistent with a central role for FFAs in metabolic infl ammation. In fact, the highest levels of FFAs in the system are found close to the site of release Abstract Subclinical infl ammation is frequently associated with obesity. Here, we aim to better defi ne the acute infl ammatory response during fasting. To do so, we analyzed representatives of immune-related proteins in circulation and in tissues as potential markers for adipose tissue infl ammation and modulation of the immune system. Lipopolysaccharide treatment or high-fat diet led to an increase in circulating serum amyloid (SAA) and 1-acid glycoprotein (AGP), whereas adipsin levels were reduced. Mouse models that are protected against diet-induced challenges, such as adiponectin-overexpressing animals or mice treated with PPAR agonists, displayed lower SAA levels and higher adipsin levels. An oral lipid gavage, as well as prolonged fasting, increased circulating SAA concurrent with the elevation of free FA levels. Moreover, prolonged fasting was associated with an increased number of Mac2-positive crown-like structures, an increased capillary permeability, and an increase in several M2-type macrophage markers in adipose tissue. This fasting-induced increase in SAA and M2-type macrophage markers was impaired in metabolically challenged animals. These data suggest that metabolic infl exibility is associated with a lack of "immunological fi tness." -Asterholm,
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».