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DANDI:001474

Obesity dysregulates feeding-evoked response dynamics in hypothalamic satiety neurons

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Claims 37

From the paper Obesity dysregulates feeding-evoked response dynamics in hypothalamic satiety neurons · claims file · checked 2026-10-21: ready

  • fig1k-early-late-recordings

    Per recording, PVH MC4R consumption responses in NCD mice are small early in the meal (Z 0.12 +- 0.11) and larger late (0.86 +- 0.09); in HFD mice they are already high early (0.72 +- 0.09) and do not increase late (0.79 +- 0.09).

    On average, neural responses were minimal in NCD-fed animals in early trials (Z-score (NCD early) = 0.12 ± 0.11), but exhibited a robust increase in late trials ... (Z-score (NCD late) = 0.86 ± 0.09) ... (Z-score (HFD early) = 0.72 ± 0.09), with no further increase observed throughout the meal (Z-score (HFD late) = 0.79 ± 0.09)

    Results, Feeding-related responses ... elevated early in a meal in HFD-fed animals, paragraph on response magnitude; Figure 1k

    How it will be judged

    Cohort 1, 60-trial sessions with at least 30 triggered trials (39 NCD, 33 HFD). Early and late values per recording as in the opening comment, under each window W (0-10, 1-10, 1-9 s) and each Z reading (Z1, Z2). Reproduced when, under one combination, all four means are within tolerance; partially reproduced when no combination puts all four in tolerance but under one NCD late is above NCD early and HFD early is above NCD early. All combinations are shown.

  • fig1k-lme

    In a linear mixed-effects model of recording-level responses with mouse as a random intercept, HFD early-meal responses exceed NCD early-meal responses and the diet by meal-phase interaction is significant.

    Linear mixed-effects model (LME), p(NCD early vs. HFD early) < 0.001, p(Diet x Meal phase) < 0.001

    Figure 1k legend; Methods, Statistical analysis

    How it will be judged

    The Methods model, Value ~ Diet * Meal phase + (1 | Mouse), statsmodels mixedlm with its defaults (REML), on two rows per recording (early, late), Diet reference NCD. The Methods say this model was used for "Fig. 1 i"; the legend places it on Fig. 1k, the recording-level panel, which is followed. Early meal as the reference level is read from the legend's "p(NCD early vs. HFD early)". Reproduced when, under one W and Z combination of fig1k-early-late-recordings, the HFD coefficient is positive with p < 0.001 and the interaction is negative with p < 0.001; partially reproduced when both hold at p < 0.05 only. All combinations are shown.

  • fig1l-early-late-mice

    Per mouse, every NCD mouse increases its response from early to late in the meal (Z 0.19 +- 0.24 to 0.91 +- 0.13), while HFD mice do not change (0.73 +- 0.19 to 0.80 +- 0.20).

    all individual NCD-fed animals exhibited an overall increase in consumption-related neural responses in the late meal phase (Z-score (NCD early) = 0.19 ± 0.24, Z-score (NCD late) = 0.91 ± 0.13)) ... This pattern was consistent across all subjects (Z-score (HFD early) = 0.73 ± 0.19, Z-score (HFD late) = 0.80 ± 0.20)

    Results, Feeding-related responses ... elevated early in a meal in HFD-fed animals, paragraph on response magnitude; Figure 1l

    How it will be judged

    Mouse values are the mean of each mouse's recording values (Methods, heatmaps and legend "by combining the sessions for each mouse"), under each W and Z reading. The legend's test is a paired, two-tailed t-test between early and late per diet; the p-values are shown only in the figure, not read here. Reproduced when, under one combination, the four means are within tolerance, all 6 NCD mice have late above early, the NCD paired t-test has p < 0.05, and the HFD paired t-test has p >= 0.05; partially reproduced when the tests come out so but a mean is out of tolerance.

  • supp1i-hfd-no-change-1-20s

    With a longer response window of 1 to 20 s after the cue, HFD mice still show no change in response from early to late in the meal.

    HFD-fed animals did not show a change in response from early to late in the meal when considering a longer window of 0–20 s post tone

    Results, Feeding-related responses ... elevated early in a meal in HFD-fed animals, paragraph on response magnitude; Supplementary Figure 1i

    How it will be judged

    A claim of absence. The Results say 0-20 s and the legend 1-20 s post-cue; both windows are run. Mouse values (6 NCD, 5 HFD mice) under each Z reading; the legend's test, a two-way ANOVA (diet x meal phase) with Tukey HSD across the four diet and phase groups. Reproduced when the Tukey comparison of HFD early against HFD late has p >= 0.05; not reproduced when p < 0.05. The difference is reported either way, as is the NCD early-late comparison.

  • supp1h-dff-early-late

    Expressed as dF/F, HFD mice have stronger consumption responses than NCD mice at the start of the meal, and these persist to the end of the feeding bout.

    at the start of the meal, HFD-fed animals exhibited stronger feeding-evoked neural responses than NCD-fed animals, and these acute responses persisted until the end of the feeding bout

    Results, Feeding-related responses ... elevated early in a meal in HFD-fed animals, paragraph 4; Supplementary Figure 1h

    How it will be judged

    No test is reported. Per-recording mean dF/F0 in the response window (each W reading), early and late meal, cohort 1. Reproduced when, under one window, the HFD early-meal mean exceeds the NCD early-meal mean and the HFD late-meal mean is at least as high as the HFD early-meal mean minus its s.e.m. over recordings.

  • fig1gh-hfd-less-ensure

    Despite calorie matching, HFD mice consume less Ensure than NCD mice, per recording session and per mouse.

    Despite calorie matching to ensure comparable acute hunger states (Fig. 1 d), the HFD animals consumed less Ensure volume during the experimental recordings (Fig. 1 g, h)

    Results, Feeding-related responses ... elevated early in a meal in HFD-fed animals, paragraph 2; Figure 1g, h

    How it will be judged

    Cohort 1. Unpaired, two-tailed Student's t-test (equal variances, scipy default), as the legend states, on per-session totals (g) and per-mouse means (h). The volume is the recorded total Ensure consumed (Methods, "The total consumed Ensure throughout the experiment was noted"); where it is not available, the number of triggered trials times ~50 uL (Methods) is the reading used, and said. The paper does not say whether sessions with fewer than 30 triggered trials are in panel g; both sets are run. Reproduced when the HFD mean is lower with p < 0.05 in both g and h under one session set; partially reproduced when in one of them.

  • fig1c-hfd-heavier

    During food restriction, HFD mice are about 30% heavier than NCD mice.

    HFD-fed mice were ~ 30% heavier than the NCD-fed mice

    Results, Feeding-related responses ... elevated early in a meal in HFD-fed animals, paragraph 2; Figure 1c

    How it will be judged

    Cohort 1 body weights during the recording period. The paper does not say which days or how they are averaged; readings are (a) the mean over recording days per mouse, then over mice; (b) the mean over all recording-day weights pooled. Reproduced when one reading is within tolerance; partially reproduced when HFD is heavier by 20% to 40%.

  • supp1cd-licking-declines

    Both NCD and HFD mice reduce their licking from the early to the late phase of the session.

    Both NCD- and HFD-fed animals steadily reduced their licking rates from early to late phases of the session

    Results, Feeding-related responses ... elevated early in a meal in HFD-fed animals, paragraph 2; Supplementary Figure 1c, d

    How it will be judged

    Supp. Fig. 1d measure, per mouse, the area under the post-cue lick-rate curve normalized to the pre-tone baseline lick rate, early against late meal. Open details, each run as a reading. Normalization is (a) subtraction of or (b) division by the mean lick rate of the 10 s before the tone; the AUC window is (i) 1-10 s post tone (the Methods' reward-window lick rate) or (ii) 0-50 s (the whole post-cue trace); the test is (x) unpaired two-tailed t-test (Supp. Fig. 1d legend) or (y) paired two-tailed t-test (Methods list Supp. Fig. 1d under paired tests). Reproduced when all readings give late below early with p < 0.05 in both diets; partially reproduced when that holds in one diet under all readings; blocked as methods_underspecified when readings disagree.

  • supp1e-hfd-less-locomotion

    Food-seeking locomotion is negligible in HFD mice compared with NCD mice, and falls further near the end of the meal.

    Compared to NCD-fed animals, food-seeking-related locomotion was negligible in HFD-fed animals ... and it was further reduced to a minimum level late near the end of the meal

    Results, Feeding-related responses ... elevated early in a meal in HFD-fed animals, paragraph 2; Supplementary Figure 1e

    How it will be judged

    No test is reported. Per mouse mean running speed over triggered trials, early and late meal, cohort 1. The window is not given in the Supp. Fig. 1e legend or the Methods; readings are (a) the whole trial, 10 s before to 50 s after the tone, and (b) the 10 s before the tone (the pre-cue period of Supp. Fig. 2g). Reproduced when, under every reading, the HFD mean over mice is below the NCD mean in both phases and the HFD late mean is below the HFD early mean; blocked as methods_underspecified when the readings disagree. Per-mouse values are shown.

  • fig2b-meal-size

    In 90-trial sessions NCD mice consume Ensure in 70.1 +- 2.1 trials and HFD mice in 52.9 +- 1.98 trials.

    NCD-fed mice consumed Ensure during 70.1 ± 2.1 out of 90 possible trials, whereas HFD-fed animals only consumed Ensure during 52.9 ± 1.98 out of 90 trials

    Results, HFD alters neural and behavioral responses ..., paragraph 1; Figure 2b

    How it will be judged

    Cohort 2, 90-trial sessions, mean over recordings. The legend names an unpaired, two-tailed Student's t-test; its p is shown only in the figure, not read here, and the text does not call the difference significant. Sessions included are open; readings are (a) all 90-trial sessions, (b) those with at least 30 triggered trials (the Methods default, and 59/54 is the count of Fig. 2a-e), (c) those with at least 15 (Fig. 2f-s). Reproduced when, under one reading, both means are within tolerance and the Student's t-test gives p < 0.05.

  • fig2c-delta-z-recordings

    Per recording, the change in response from early to late in the meal is 0.52 +- 0.09 in NCD mice and only 0.12 +- 0.08 in HFD mice.

    in NCD-fed animals, excitatory responses increased over the meal, with a positive mean change in Z-score (ΔZ-score) between early and late in the meal of 0.52 ± 0.09. However, in HFD-fed animals, the increase was minimal (ΔZ-score = 0.12 ± 0.08; Fig. 2 c)

    Results, HFD alters neural and behavioral responses ..., paragraph 1; Figure 2c

    How it will be judged

    Cohort 2, recordings with at least 30 triggered trials (59 NCD, 54 HFD). Delta Z-score under D5 and D15, each W (1-9, 1-10 s) and Z reading. The legend's test is an unpaired two-tailed Student's t-test. Reproduced when, under one combination, both means are within tolerance and the t-test gives NCD above HFD with p < 0.05; partially reproduced when the t-test holds but a mean is out of tolerance. All combinations are shown.

  • fig2d-delta-z-mice

    Per mouse, the early-to-late change in response is 0.56 +- 0.10 in NCD mice and 0.28 +- 0.09 in HFD mice.

    Similar results were observed across individual animals (ΔZ-score: NCD = 0.56 ± 0.10, HFD = 0.28 ± 0.09) (Fig. 2 d)

    Results, HFD alters neural and behavioral responses ..., paragraph 1; Figure 2d

    How it will be judged

    As fig2c-delta-z-recordings, with each mouse's value the mean of its recordings' delta Z-scores (legend, "averaged across sessions"), 7 NCD and 7 HFD mice, unpaired two-tailed Student's t-test. Reproduced when, under one combination, both means are within tolerance and NCD is above HFD with p < 0.05; partially reproduced when the means hold and the test does not.

  • fig2e-lick-vigor

    Throughout the 90-trial meal NCD mice lick at a higher rate during the cue than HFD mice; NCD licking begins to decline after about 50 trials and HFD licking after about 20.

    Throughout the meal, NCD-fed animals exhibited higher licking vigor than HFD-fed animals (Fig. 2 e). In NCD-fed animals, licking vigor began to decline steadily after ~ 50 trials ... in HFD-fed animals, licking vigor began to decline much earlier, after only ~ 20 trials

    Results, HFD alters neural and behavioral responses ..., paragraph 2; Figure 2e

    How it will be judged

    Cue lick rate is licks per second in the 0-1 s tone window (Methods), triggered trials only, per trial index 1 to 90, averaged across mice (legend) of recording means, cohort 2 recordings with at least 30 triggered trials. "Throughout" has two readings, NCD above HFD (a) at every trial index both groups have data or (b) in every 15-trial block. Onset of decline is not defined; readings are (i) the trial index of the maximum of the curve smoothed with a 15-trial moving mean, (ii) the first trial after which the 15-trial moving mean stays below the mean of the first 15 trials. Reproduced when NCD is higher under one reading and both onsets are within tolerance under one reading; partially reproduced when NCD is higher and the NCD onset is later than the HFD onset but the onsets are out of tolerance.

  • fig2fj-early-lick-by-meal-size

    Sessions with smaller meals have lower lick rates early in the meal; initial cue lick rates span 4 to 5.5 licks/s across NCD meal-size groups and 2 to 5.7 licks/s across HFD groups.

    Sessions with smaller meal sizes (fewer total triggered trials and lower caloric intake) exhibited lower lick rates early in the meal (i.e., the initial lick rate during the cue was 4–5.5 licks/s for NCD mice versus 2–5.7 licks/s for HFD mice)

    Results, HFD alters neural and behavioral responses ..., paragraph 3; Figure 2f-j, p

    How it will be judged

    Cohort 2 sessions with at least 15 triggered trials, grouped by triggered trials (15-29, 30-44, 45-59, 60-74, 75-90). "Initial lick rate" is open; readings are (a) the group mean cue lick rate of the first triggered trial, (b) of the first 15 triggered trials. Reproduced when, under one reading, the lowest and highest group means of each diet are within tolerance of the reported bounds and, in each diet, the smallest meal-size group has a lower mean than the largest.

  • fig2p-lick-rate-meal-size

    The mid-meal cue lick rate correlates positively with meal size in both NCD and HFD sessions.

    lick rate early in the meal positively correlated with the number of trials triggered in the session for both diet groups (Fig. 2 p)

    Results, HFD alters neural and behavioral responses ..., paragraph 6; Figure 2p

    How it will be judged

    Pearson correlation (legend) per diet over recordings with at least 15 triggered trials, of meal size (triggered trials) with the cue lick rate averaged over the 15th to 29th triggered trial (legend); the Results' "early in the meal" (first 15 triggered trials) is a reading too. Reproduced when, under one reading, r > 0 with p < 0.05 in both diets; partially reproduced in one.

  • fig2km-elevated-early-at-matched-licking

    In sessions of 45 to 74 triggered trials, where early licking vigor is comparable between groups, HFD mice still have larger PVH MC4R responses early in the meal than NCD mice.

    Critically, despite both HFD- and NCD-fed mice having similar licking vigor early during a session (e.g., Fig. 2 h), HFD-fed mice still showed elevated PVH MC4R responses in the early trials (e.g., Fig. 2 m)

    Results, HFD alters neural and behavioral responses ..., paragraphs 4 and 5; Figure 2g, h, l, m

    How it will be judged

    No test is reported. Within the 45-59 and 60-74 meal-size groups, the mean over recordings of the early-meal response (first 15 triggered trials, each W and Z reading) and of the early-meal cue lick rate. Reproduced when, under one combination, in both groups the HFD early response mean exceeds the NCD mean by more than the sum of their s.e.m.s while the HFD and NCD early lick-rate means differ by less than the sum of their s.e.m.s; partially reproduced when that holds in one group.

  • fig2q-midmeal-response-meal-size

    In HFD sessions, mid-meal PVH MC4R responses correlate negatively with meal size (r = -0.46, p = 0.001).

    the PVH MC4R responses in HFD-fed animals negatively correlated with meal size (HFD: r = − 0.46, p = 0.001)

    Results, HFD alters neural and behavioral responses ..., paragraph 6; Figure 2q

    How it will be judged

    Mid-meal response is the mean response over the 15th to 29th triggered trial (legend), each W and Z reading; recordings with at least 15 triggered trials (Results, "in sessions with at least 15 triggered trials"), and with at least 30 as a reading (Methods default). Reproduced when, under one combination, r is within tolerance and p < 0.05; partially reproduced when r < 0 with p < 0.05 but out of tolerance. The NCD correlation is reported.

  • fig2r-weight-midmeal-response

    In HFD mice, absolute body weight on the recording day correlates positively with mid-meal Z-scored responses.

    We found that absolute body weight positively correlated with mid-meal Z-scored MC4R activity for HFD mice, indicating that heavier HFD mice exhibit stronger neuronal activation during the meal (Fig. 2 r)

    Results, HFD alters neural and behavioral responses ..., paragraph 7; Figure 2r

    How it will be judged

    Pearson correlation (legend) over HFD recordings of the recording-day body weight with the mid-meal response, under the readings of fig2q-midmeal-response-meal-size. Reproduced when, under one reading, r > 0 with p < 0.05; partially reproduced when r > 0 and p >= 0.05.

  • fig2s-weight-meal-length

    In HFD mice, meal length (triggered trials) correlates negatively with absolute body weight.

    meal length (i.e. the number of triggered trials) correlated negatively with absolute body weight in HFD-fed animals (Fig. 2 s)

    Results, HFD alters neural and behavioral responses ..., paragraph 7; Figure 2s

    How it will be judged

    Pearson correlation (legend) over HFD recordings, with at least 15 and, as a reading, at least 30 triggered trials. Reproduced when, under one reading, r < 0 with p < 0.05; partially reproduced when r < 0 and p >= 0.05.

  • supp2a-volume-trials

    Ensure volume consumed correlates robustly with the number of triggered trials in both diet groups, so meal size is defined as triggered trials.

    there was a robust correlation between volume of Ensure consumed and number of triggered trials for both NCD- and HFD-fed animals

    Results, HFD alters neural and behavioral responses ..., paragraph 1; Supplementary Figure 2a

    How it will be judged

    No test is named; Pearson correlation, the paper's test for its other meal-size correlations (Fig. 2p-s), per diet over cohort 2 recordings with a recorded Ensure volume. Reproduced when r > 0 with p < 0.05 in both diets.

  • supp2h-delta-z-meal-size

    Across sessions, the within-meal change in response correlates with meal size with r = -0.34 (p = 0.012) in NCD mice and r = 0.26 (p = 0.048) in HFD mice. The sentence calls the NCD correlation positive and the HFD one negative, opposite to the printed signs.

    This analysis revealed a positive correlation in the NCD-fed group and a negative correlation in the HFD-fed group (NCD: r = − 0.34, p = 0.012, HFD: r = 0.26, p = 0.048)

    Results, HFD alters neural and behavioral responses ..., paragraph 9; Supplementary Figure 2h

    How it will be judged

    Per diet over cohort 2 recordings, Pearson correlation of triggered trials with the delta Z-score, read as the legend's late-meal minus early-meal mean (D15) and as the Methods' D5, each W and Z reading. Reproduced when, under one combination, both r are within tolerance with p < 0.05. If instead the signs come out as the sentence's words (NCD positive, HFD negative, both p < 0.05), partially reproduced, noting that the words and numbers disagree.

  • supp2fg-locomotion-not-meal-size

    HFD mice show reduced locomotion, but locomotion does not correlate with meal size.

    Although HFD-fed animals exhibited reduced locomotion, this did not correlate with meal size (Supplementary Fig. 2f, g)

    Results, HFD alters neural and behavioral responses ..., paragraph 8; Supplementary Figure 2f, g

    How it will be judged

    The paper names no test for either part. Locomotion is the mean running speed in the pre-cue period (Supp. Fig. 2g legend) over triggered trials, per recording. Reduced locomotion holds when the HFD mean over recordings is below the NCD mean. The absence of a correlation is judged with Pearson correlation of triggered trials against locomotion per diet (the paper's test for its other meal-size correlations, a choice recorded as a deviation); reproduced when p >= 0.05 in both diets and HFD locomotion is lower; not reproduced when either correlation has p < 0.05. Locomotion after reward (1-10 s) is shown as a variant.

  • supp2j-variability-weight

    Pre-Ensure spontaneous signal variability correlates weakly with absolute body weight in HFD mice.

    Our analysis revealed a weak correlation when assessing absolute body weight for HFD-fed animals (Supplementary Fig. 2 j)

    Results, HFD alters neural and behavioral responses ..., paragraph 10; Supplementary Figure 2i, j

    How it will be judged

    Variability is a rolling standard deviation of dF/F0 in the period before the first Ensure delivery, averaged per recording; the rolling window length and the F0 for this continuous trace are not given anywhere. Readings for the window are 1 s, 10 s and 60 s, and F0 is the mean of the pre-Ensure period. Pearson correlation over HFD recordings with recording-day body weight. Reproduced when all readings give p < 0.05 with |r| below 0.5 (the paper's "weak"); blocked as methods_underspecified when readings disagree.

  • supp2k-sex-early-response

    NCD females show slightly larger early-meal responses than males, a difference more pronounced in HFD mice.

    NCD-fed females exhibited slightly larger neural responses than males early in the meal ... a trend that was even more pronounced in HFD-fed animals

    Results, HFD alters neural and behavioral responses ..., paragraph 11; Supplementary Figure 2k

    How it will be judged

    No test is reported. Mean over recordings of the early-meal response (first 15 triggered trials) for M-NCD, F-NCD, M-HFD, F-HFD (26, 33, 31, 23 recordings), each W and Z reading. Reproduced when, under one combination, F exceeds M in both diets and the F minus M difference is larger in HFD than in NCD.

  • supp2lp-fasting-no-effect

    An additional overnight fast does not significantly alter licking or PVH MC4R response dynamics in either diet group.

    However, additional fasting did not significantly alter licking or PVH MC4R response dynamics for either group (Supplementary Fig. 2l–p)

    Results, HFD alters neural and behavioral responses ..., paragraph 12; Supplementary Figure 2l-p

    How it will be judged

    A claim of absence for which the paper names no test. Fasted against nonfasted recordings within each diet (NCD 28 and 31, HFD 23 and 31), on the mean cue lick rate over triggered trials, the early-meal response and the delta Z-score (D15), each W and Z reading. Readings for the test are (a) an unpaired two-tailed Student's t-test on recordings, the paper's test for recording comparisons in Fig. 2b-c, and (b) a linear mixed-effects model, measure ~ fasting + (1 | Mouse), the paper's model for repeated sessions. Reproduced when every reading gives p >= 0.05 for every measure in both diets; not reproduced when every reading finds some effect at p < 0.05; blocked as methods_underspecified when they disagree. Effect sizes are reported.

  • supp2q-hfd-more-training

    HFD mice needed more training sessions than NCD mice to reach stable task performance.

    Although HFD mice required more sessions to reach stable task performance (Supplementary Fig. 2q)

    Methods, Behavioral training on wheels; Supplementary Figure 2q

    How it will be judged

    Unpaired two-tailed Student's t-test (Methods, statistical analysis, item 3) on the number of training sessions per mouse. Reproduced when HFD is higher with p < 0.05. Testable only if training sessions are in the dataset.

  • fig3h-early-response-diet-switch

    After switching from HFD to NCD, early-meal PVH MC4R responses fall from their level on HFD toward NCD levels, while HFD->HFD mice keep high early-meal responses.

    PVH MC4R neuron responses remained attenuated relative to prior responses while on HFD for most of the experiment (Fig. 3 f, h)

    Results, Effects of diet switching ..., paragraphs 2 and 5; Figure 3h

    How it will be judged

    Early-meal response per recording (first 15 triggered trials, W 1-9 and 1-10 s, each Z reading), recordings with at least 30 triggered trials, six groups (NCD->NCD, HFD->NCD, HFD->HFD, each before and after the switch). The legend's test, a two-way ANOVA (condition x phase) with Tukey HSD across the six groups. Reproduced when, under one combination, HFD->NCD after is below HFD->NCD before with Tukey p < 0.05 and HFD->HFD after is not below HFD->HFD before at p < 0.05; partially reproduced when HFD->NCD after is lower but not significantly. The before-switch HFD groups against NCD->NCD are reported.

  • fig3i-ncd-increase-only

    After the diet switch, NCD->NCD mice show a significant increase in response from early to late in the meal, while HFD->NCD mice show only a slight, nonsignificant increase.

    The HFD → NCD group displayed an intermediate pattern between the HFD → HFD and NCD → NCD groups, with a slight but nonsignificant increase in PVH MC4R responses across the meal

    Results, Effects of diet switching ..., paragraph 4; Figure 3i; Supplementary Figure 3i

    How it will be judged

    Second-diet recordings. Two tests the paper names, both run. (1) The Fig. 3i LME, Value ~ C(Condition, Treatment('NCD|NCD')) * Meal phase + (1 | Mouse) on two rows per recording; within-group early-late effects are the meal-phase coefficient with each group in turn as reference. (2) The Supp. Fig. 3i paired two-tailed t-test on mouse means. The NCD->NCD increase is reproduced when both give late above early with p < 0.05 under one W and Z combination. The HFD->NCD part is a claim of absence, judged on these two tests; reproduced when neither finds p < 0.05 and the late mean is above the early mean, not reproduced when both do, and blocked as methods_underspecified when they disagree. HFD->HFD is reported.

  • fig3j-delta-z-diet-switch

    After the switch, the per-mouse early-to-late change in response is 0.37 +- 0.03 in NCD->NCD, 0.14 +- 0.05 in HFD->NCD and -0.05 +- 0.07 in HFD->HFD mice; it is significantly smaller in HFD->HFD.

    we observed a significantly smaller increase in neural responses across trials in the HFD → HFD group ... six weeks of NCD exposure in formerly HFD-fed animals failed to fully restore this effect to NCD levels (ΔZ-score: NCD → NCD = 0.37 ± 0.03, HFD → NCD = 0.14 ± 0.05, HFD → HFD = − 0.05 ± 0.07)

    Results, Effects of diet switching ..., paragraph 4; Figure 3j

    How it will be judged

    Second-diet recordings with at least 30 triggered trials; mouse values are means of recording delta Z-scores, D5 (the Methods name Fig. 3j) and D15, each W and Z reading. One-way ANOVA with Tukey HSD (legend). Reproduced when, under one combination, the three means are within tolerance and HFD->HFD is below NCD->NCD with Tukey p < 0.05; partially reproduced when the order NCD->NCD > HFD->NCD > HFD->HFD holds and the Tukey test does, with means out of tolerance.

  • fig3k-ensure-after-switch

    After the switch, HFD->NCD mice consume as much Ensure per session as NCD->NCD mice and significantly more than HFD->HFD mice.

    the HFD → NCD group consumed a volume of Ensure comparable to the NCD → NCD group and significantly higher than the HFD → HFD group during individual recording sessions (Fig. 3 k)

    Results, Effects of diet switching ..., paragraph 4; Figure 3k

    How it will be judged

    Ensure volume per recording (recorded total; triggered trials times ~50 uL as a reading where the total is absent), six groups (three conditions before and after), two-way ANOVA (condition x phase) with Tukey HSD (legend). Whether recordings with fewer than 30 triggered trials are included is open; both sets are run. Reproduced when, under one set, HFD->NCD after exceeds HFD->HFD after with p < 0.05 and the Tukey test of HFD->NCD after against NCD->NCD after gives p >= 0.05; partially reproduced when only the first holds.

  • fig3-hfd-hfd-short-meals

    In the second diet phase, HFD->HFD mice stop consuming Ensure early, never exceeding 60 triggered trials.

    The HFD → HFD group maintained high early-meal PVH MC4R responses (Fig. 3 d, g, h) and ceased to engage in Ensure consumption even earlier in the session, never exceeding 60 triggered trials

    Results, Effects of diet switching ..., paragraph 2; Figure 3d, g

    How it will be judged

    Over all second-phase HFD->HFD 90-trial recordings. Reproduced when no session has more than 60 triggered trials; partially reproduced when no more than one of the 23 sessions does.

  • fig3c-hfd-ncd-licking-recovers

    After at least six weeks on NCD, formerly HFD mice lick with more vigor during the cue, a reinstated motivation to consume food.

    After at least six subsequent weeks on NCD, these same animals displayed an increase in licking vigor during cue presentation (Fig. 3 c (bottom right panel), Supplementary Fig. 3f)

    Results, Effects of diet switching ..., paragraph 2; Figure 3c; Supplementary Figure 3f

    How it will be judged

    No test is reported. Cue lick rate (0-1 s) over triggered trials per trial index, averaged across HFD->NCD recordings with at least 30 triggered trials (Supp. Fig. 3f legend), before against after the switch. Reproduced when the after curve's mean over trials 1-90 (each trial index weighted equally, indices with data in both phases) is above the before curve's and the mean over recordings of each recording's mean cue lick rate is higher after as well.

  • supp3c-ncd-hfd6w-dynamics-retained

    NCD mice switched to HFD for 6 weeks keep their response dynamics, with a significant early-to-late increase in response after the switch, comparable to the change before it, and stable licking vigor.

    the NCD → HFD 6w group retained their response properties, exhibiting comparable changes in response magnitude before (NCD) and after the diet switch (HFD 6w ) between early and late meal stages, despite a significant weight gain after the diet switch

    Results, Effects of diet switching ..., paragraphs 3 and 4; Supplementary Figure 3a-d, h

    How it will be judged

    Supp. Fig. 3c (1-9 s) and 3d (1-19 s) windows, each Z reading; mouse means of early and late meal responses, paired two-tailed t-test (legend), in the NCD phase and the HFD6w phase. The text calls only the second-phase increase significant; "comparable" before the switch is read as the same paired test also giving late above early with p < 0.05 in the NCD phase. Reproduced when late exceeds early with p < 0.05 in both phases under one Z reading in the 1-9 s window; partially reproduced when in the HFD6w phase only. Licking stability is reported as the mean cue lick rate per phase, not judged.

  • supp3j-body-weight-switch

    NCD->HFD6w mice gain significant body weight over the 6-week HFD phase, while HFD->NCD mice do not lose weight (a slight, nonsignificant gain).

    these animals showed a significant increase in body weight during the 6-week HFD phase (Supplementary Fig. 3j)

    Results, Effects of diet switching ..., paragraphs 3, 4 and 7; Supplementary Figure 3j

    How it will be judged

    The Methods model, per condition, body weight ~ phase + (1 | Mouse) on recording-day weights, statsmodels mixedlm. Reproduced when the NCD->HFD6w phase effect is positive with p < 0.05 and the HFD->NCD phase effect has p >= 0.05 and is not negative with p < 0.05 (absence, judged on this model); partially reproduced when only the first holds.

  • supp3m-weight-gain-response

    In the second diet phase, mid-meal responses correlate positively with weight gain in NCD->HFD6w mice (r = 0.53, p = 0.001) and also in NCD->NCD mice (r = 0.46, p = 0.003).

    we observed a strong positive correlation (r = 0.53, p = 0.001) between mid-meal neural responses and the diet-induced weight gain in the NCD → HFD 6w group during the second diet phase ... we also observed a positive correlation in the NCD → NCD group (r = 0.46, p = 0.003)

    Results, Effects of diet switching ..., paragraph 6; Supplementary Figure 3m (text) or 3n (legend)

    How it will be judged

    Per second-phase recording, mid-meal response (15th-29th triggered trial, each W and Z reading) against weight on the recording day (C) relative to weight at the start of ad libitum feeding (A), as the Supp. Fig. 3n legend defines it (the text cites panel m, whose legend is meal size). "Relative to" is read as C - A and as C / A. Reproduced when, under one combination, both r are within tolerance with p < 0.05; partially reproduced when both are positive with p < 0.05.

  • supp3l-weight-not-meal-length

    In the second diet phase, absolute body weight does not predict meal length in NCD->NCD or NCD->HFD6w mice.

    absolute body weight does not predict meal length in animals exposed to NCD or HFD 6w during the second meal phase (Supplementary Fig. 3l)

    Results, Effects of diet switching ..., paragraph 6; Supplementary Figure 3l

    How it will be judged

    A claim of absence; the test is Pearson correlation, read from the linear fits of the legend and the paper's correlations in this section. Per group, second-phase recordings, triggered trials against recording-day body weight. Reproduced when p >= 0.05 in both groups; not reproduced when either has p < 0.05.

  • supp3q-hfd-ncd-weight-loss-meal-length

    In HFD->NCD mice, meal length correlates negatively with weight change, so mice that lost more weight before the session tended to eat larger meals; neural responses do not correlate with weight change.

    In the HFD → NCD group, we observed no correlation with neural responses (Supplementary Fig. 3j, p), but a significant negative correlation between meal length and weight change, indicating that animals that lost more weight before the session tended to have larger meals

    Results, Effects of diet switching ..., paragraph 7; Supplementary Figure 3p, q

    How it will be judged

    Second-phase HFD->NCD recordings. Weight change is open; the text gives body weight relative to (a) the maximum ad libitum weight or (b) the weight before HFD exposure, and the legend relative to the start of ad libitum feeding (A); each as a difference and as a ratio. Pearson correlation of triggered trials with weight change. The "no correlation with neural responses" is cited to Supp. Fig. 3p, whose legend correlates mid-meal response with meal size, while the text pairs it with weight change; both are run, mid-meal response (15th-29th triggered trial, each W and Z reading) against (i) weight change and (ii) triggered trials. Reproduced when, under one weight-change reading, the first has r < 0 with p < 0.05 and the neural correlations have p >= 0.05 under both (i) and (ii); partially reproduced when the first holds and only one of (i) and (ii) has p >= 0.05.

Pipeline

Paper
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Claims
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Claims check
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Attempt
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