Intact innervation is essential for diet-induced recruitment of brown adipose tissue
Part of the results reproduced; minor but material deviations remained.
Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
- ✓No relevant deviation in data/preprocessing
- ✓No authors-side cause for any deviation
- ✓Any deviation was negligible
- 🔴Could not use the authors’ exact input data
- 🔴Reported values were only indirectly comparable
- 🟡Reported values were not (fully) derivable from the shared data
- 🟡The central claim did not (fully) hold under reproduction
- 🟡Overall, the reproduction showed a material discrepancy
▸Reproduction agent’s raw note
DROP (non_pipeline). 'Intact innervation is essential for diet-induced recruitment of brown adipose tissue' (Fischer AW, Schlein C, Cannon B, Heeren J, Nedergaard J; Am J Physiol Endocrinol Metab 2019; PMID 30576247; PMCID PMC6459298; DOI 10.1152/ajpendo.00443.2018) is a pure wet-lab / in-vivo mouse physiology study. Methods are surgical denervation of interscapular BAT, Western blot (Li-Cor Image Studio Lite densitometry), qRT-PCR (TaqMan), indirect calorimetry (TSE PhenoMaster), immunofluorescence/IHC, and H&E histology; statistics by Student's t-test in GraphPad Prism 6 / Excel. There is NO bioinformatic or computational pipeline, NO RNA-seq/microarray/sequencing, NO deposited public dataset (GEO/SRA/ENA/ArrayExpress/figshare/zenodo/dbGaP/EGA/PRIDE all checked: zero accessions), NO Data/Code Availability statement, and NO analysis-code repository. Therefore there is nothing to reproduce computationally and no third-party tool applies (no deposited data to run one on). No «our HPC» compute was spent (correctly). This is an honest, valid drop, not a reproduction failure: the experimental science is sound but is out of scope for computational-pipeline reproduction. Headline reported claims (c1-c8) are documented in original/claims.tsv for the human audit trail only and were NOT attempted. Secondary applicable reasons: no_code, no_data_accession.
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v1 current initial assessmentassessed: 2026-06-18 ⛓ dab66d36b725
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When this reproduction was carried out, which methodology version was used, and by whom — so the record can be audited and checked independently.
- Reproduced
- 2026-06-18
- Rubric version
- v1.0
- Assessed by
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🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-18no human curator yet
- Last updated
- 2026-08-05
Provisional, curator- or AI-assessed, and independently checkable. A reproduction outcome states what one attempt could reproduce — not a judgement of the authors.
Deep full-text extraction
Model: sonnetWhether the recruitment of brown adipose tissue (BAT) during diet-induced thermogenesis (DIT) requires intact sympathetic innervation of the tissue, or whether circulating/humoral factors alone can drive this recruitment under obesogenic conditions.
- ★ Intact innervation of BAT is essential for diet-induced thermogenesis/recruitment. finding
- ★ Circulating factors cannot by themselves initiate recruitment of brown adipose tissue under obesogenic conditions. finding
- ★ Denervation totally abolished the diet-induced increase in total UCP1 protein levels seen in intact mice, while basal UCP1 expression was innervation-independent. finding
- ★ IBAT denervation did not enhance obesity but increased metabolic efficiency, so equal obesity was reached with lower food intake. finding
- Denervation altered the feeding pattern of the mice. finding
- Denervation of interscapular BAT did not detectably hyper-recruit other BAT depots. finding
- No UCP1 protein was detected in the browning-competent inguinal white adipose tissue depot under any tested condition. finding
- Surgical denervation method for interscapular BAT (cutting nerve bundles at two locations, removing intermediate piece) as established by Vaughan et al. method
| Assay | System | Perturbation | Readout | Platform |
|---|---|---|---|---|
| surgical denervation with body weight/food intake monitoring | interscapular BAT (IBAT), male C57BL/6J mice | surgical denervation vs. sham, chow vs. high-fat diet, thermoneutrality (30°C) | body weight gain, food/energy intake, metabolic efficiency | — |
| indirect calorimetry | whole-body, male C57BL/6J mice | IBAT denervation vs. sham, chow vs. HFD | O2 consumption, CO2 production, energy expenditure, respiratory quotient, food/water intake | TSE PhenoMaster System (TSE Systems) |
| Western blotting | interscapular BAT and other adipose depots | IBAT denervation vs. sham, chow vs. HFD | UCP1, tyrosine hydroxylase, and γ-tubulin protein levels | Amersham Imager 600 (GE); Li-Cor Image Studio Lite |
| quantitative real-time PCR (TaqMan) | adipose tissue (IBAT and other depots) | IBAT denervation vs. sham, chow vs. HFD | mRNA levels of Ucp1, Adrb3, Dio2 (normalized to Tbp) | 7900HT Fast Real-Time PCR System (Applied Biosystems) |
| histology (H&E staining) | IBAT sections | IBAT denervation vs. sham, chow vs. HFD | tissue morphology | Leica Microtome/Autotechnikon |
| immunofluorescence/confocal imaging | IBAT sections | IBAT denervation vs. sham | tyrosine hydroxylase and perilipin1 staining (innervation confirmation, adipocyte marker) | Nikon A1 Ti confocal laser scanning microscope |
- – Body weight of chow-fed mice was stable and unaffected by IBAT denervation.
- ▲ HFD feeding caused significant weight gain, not affected by IBAT denervation.
- – HFD mice had significantly higher energy intake than chow, statistically similar (slightly lower trend) in denervated mice.
- ▲ Metabolic efficiency (body weight gained per food energy) was significantly higher in IBAT-denervated mice than sham.
- ▼ Denervation abolished the diet-induced increase in total UCP1 protein observed in intact (sham) mice.
- – No UCP1 protein detected in inguinal WAT under any diet or denervation condition.
- pvalue P ≤ 0.001 between diets; P ≤ 0.05 between surgical intervention groups (Figure 1 body weight/metabolic efficiency comparisons)
- other IBAT estimated to contribute ~70% (or ~25% by another method) of total BAT thermogenic potential (relative contribution of IBAT depot to whole-body BAT thermogenesis)
- other ~45% of total UCP1 mRNA in IBAT, ~50% in other BAT depots, ~5% in brite/beige depots at 30°C (distribution of UCP1 mRNA across adipose depots in mice at thermoneutrality)
Statistical methods review
Model: sonnetA neutral, descriptive read of the statistical approach — what was done, and (for shared learning, not as criticism) what could also have been done.
The study used a 2×2 between-subjects design (diet: chow vs. high-fat × surgery: sham vs. interscapular BAT denervation) with male C57BL/6J mice (n = 5 per group) housed at thermoneutrality (30°C). Student's t-test was the sole stated inferential test, applied separately to detect diet effects and denervation effects across all outcomes (body weight, energy intake, metabolic efficiency, UCP1 protein/mRNA, calorimetry). Results were expressed as means ± SE with threshold-based p-value notation (asterisks for diet effect, hash symbols for denervation effect) rather than exact p-values.
| Test | Applied to | n | Assumptions |
|---|---|---|---|
| Student's t-test (direction/tails not stated) | Diet effect (chow vs. HFD): body weight gain, energy intake, metabolic efficiency (Fig. 1C–F) | n = 5 per group | not stated |
| Student's t-test (direction/tails not stated) | Denervation effect (sham vs. DNV): body weight gain, energy intake, metabolic efficiency (Fig. 1C–F) | n = 5 per group | not stated |
| Student's t-test (direction/tails not stated) | UCP1 protein levels and mRNA (Western blot and qRT-PCR; diet and denervation effects; figures not fully visible in provided text) | n = 5 per group (inferred from stated n; exact n per blot not stated in provided text) | not stated |
| Student's t-test (direction/tails not stated) | Indirect calorimetry outcomes (energy expenditure, RQ, food intake during calorimetry; Fig. 3) | n = 5 per group (inferred; exact n per calorimetry measurement not stated in provided text) | not stated |
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The 2×2 factorial design (diet × surgery) was analyzed by applying Student's t-tests separately for each factor across each outcome↳ Could also: A two-way ANOVA followed by a post-hoc test (e.g., Tukey HSD or Sidak) for each outcome variable could also have been applied — Two-way ANOVA directly tests the diet × denervation interaction term, which is central to the paper's question of whether denervation modifies the diet effect; applying separate t-tests does not formally test this interaction and can inflate type I error across the factorial comparisons
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Multiple Student's t-tests were conducted across numerous outcome variables (body weight, energy intake, metabolic efficiency, UCP1 protein, multiple mRNA targets, calorimetry variables) without a stated correction for multiple comparisons↳ Could also: A multiplicity correction such as Benjamini-Hochberg FDR adjustment or Holm-Bonferroni could also have been applied across the family of tests — With many simultaneous tests, the probability of at least one false-positive result increases; a correction procedure makes the accepted type I error rate explicit and consistent across the study
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Dispersion was reported as SEM (means ± SE) with n = 5 per group↳ Could also: SD or 95% confidence intervals could also have been used to describe spread — With n = 5, SEM is approximately half the SD, which can make variability appear smaller than it is; SD directly describes the observed biological variability in the sample, and 95% CIs additionally convey uncertainty about the group mean estimate, both of which are often preferred for small-n experiments
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P-values were reported as threshold bands (*, **, ***) rather than exact values↳ Could also: Exact p-values (e.g., P = 0.023) could also have been reported — Exact p-values allow readers to apply their own significance thresholds, facilitate meta-analysis, and are recommended by many journals and statistical reporting guidelines (e.g., APA, Nature reporting standards)
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No effect size metrics were reported alongside significance tests↳ Could also: Cohen's d (for t-tests) or partial η² (for ANOVA) could also have been reported — With n = 5, studies are underpowered to detect small effects, so reporting effect sizes helps readers evaluate biological magnitude independently of statistical significance and supports future power calculations
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UCP1 Western blot signals were quantified as continuous outcomes and compared with t-tests; the provided text does not indicate whether normality was assessed for the small groups↳ Could also: A nonparametric alternative such as the Mann-Whitney U test could also have been applied for pairwise comparisons with n = 5 — With only 5 observations per group, normality assumptions are difficult to verify empirically; nonparametric tests make no distributional assumption and are a common choice for small-n Western blot quantification data
What was reproduced
The exact results taken into scope, with each reported value next to the value our attempt produced.
NOTHING — DROP (non_pipeline). Pure wet-lab/in-vivo mouse physiology study
(surgical iBAT denervation; Western blot, qRT-PCR, indirect calorimetry,
histology/IF). No bioinformatic pipeline, no deposited data, no code. See
reproduction/scope.md and reproduction/ROOM_RESULT.json.
No individual results have been recorded for this entry yet.
Assessments & scoring basis
Each contributor’s verdict, the per-question basis, and the auditable, itemised worksheet behind it.
An automated assessment. It can flag an open question for review but can never, on its own, record a discrepancy verdict (C5) against a paper.
Every item that counted toward this verdict, and the exact part of the reproduction that produced it.
This is a valid, honest non_pipeline drop, not a reproduction failure. The paper (Fischer/Schlein/Nedergaard, Am J Physiol Endocrinol Metab 2019, PMC6459298) is pure wet-lab/in-vivo mouse physiology — denervation, Western blot, qRT-PCR, TSE PhenoMaster calorimetry, histology — with no computational pipeline, no code, and no deposited data (all major repositories checked, zero accessions). Nothing could be compared 1:1 (q1/q2 red) because nothing was shared, but per the rubric this is a data-availability/scope limitation on the input side, not an authors' defect or fabrication signal (no too-perfect pattern; q5 yellow only because non-derivable, not suspect). The core claim is simply untestable in this framework, so q7/q8 are yellow rather than red.
Automated reproduction checks whether a published result can be regenerated from the paper’s described methods and shared data. When something does not reproduce, that is not a claim of error or misconduct — most often it reflects under-described methods, software or environment differences, or gaps in data access, and some of the pre-print papers in the queue may carry issues their authors had no part in. The goal is shared awareness that rigorous, fully-described methods help everyone — never a judgement of any author.
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Reproduction footprint
claude-opus-4-8Measured resources invested to assess this paper — sanitised (machine class only, no job ids/paths). Compute = HPC accounting (SLURM); tokens = the AI agent's session.