Lack of “immunological fitness” during fasting in metabolically challenged animals
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".