Gut Microbiota Restores Central Neuropeptide Deficits Present in Germ Free Animals
Bibliographic record
Abstract
Recent work has shown that gut microbiota plays an important role in host energy homeostasis. Indeed, germ‐free (GF) mice have lower levels of adiposity and leptin levels compared to conventionalized mice. Additionally, GF mice are resistant to obesity when placed on a high‐fat diet. Studies show that gut microbiota contributes to obesity by increasing energy extraction, promoting inflammation, and altering lipogenic and adipogenic enzymes. Moreover, recent work demonstrates the ability of the microbiota to alter expression and release of gut peptides that control appetite and regulate energy homeostasis. However, little is known about the neuronal response of these hormones in GF animals, especially leptin, which is strikingly decreased in these animals. Therefore, we aimed to determine the sensitivity of leptin in GF mice compared to conventional mice by injecting leptin and measuring levels of leptin receptor activation via STAT3 and PI3K pathways in the hypothalamus and hindbrain. We also measured expression of orexigenic and anorexigenic peptides in the hypothalamus and hindbrain to examine whether gut microbiota impacts central nervous system regulation of energy homeostasis. We found that GF mice had a significant increase in hypothyalamic NPY and AgRP mRNA expression and a decrease in hindbrain NPY and AgRP mRNA. mRNA expression of POMC and CART remained unchanged. Protein expression of hypothalamic STAT3 and pERK/ERK increased significantly in response to peripheral leptin. Further, administration of leptin normalized circulating levels of leptin, GLP‐1, PYY and ghrelin, all of which were significantly decreased in GF mice. Conventionalization of GF mice (10 days) restored the deficits in hypothalamic and hindbrain neuropeptides present in GF animals. These results show that gut microbiota regulates hypothalamic and hindbrain orexigenic/anorexigenic neuropeptide expression. This is in line with the role of gut microbiota in lipid metabolism and fat deposition that may contribute to excess fat in conventionalized animals under high feeding condition. Support or Funding Information Romanian National Program PN‐II‐ID‐PCE‐2012‐4‐0608 no. 48/02.09.2013, “Analysis of novel risk factors influencing control of food intake and regulation of body weight”
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".