SUPPLEMENTAL INFORMATION LISTING

I. Supplemental Figures’ Legend. For each repeated-measures test presented in the main body of the report, body weight measurements taken immediately prior to testing are presented in the odd-numbered supplemental figures (in the order that the tests are presented in the main body). Also, corresponding normalized (in the cases of glucose tolerance tests) or absolute (in the cases of insulin tolerance or pyruvate conversion tests) glucose concentration-based glucose excursion curves for each repeated-measures test are presented in the even-numbered supplemental figures (in the order that the tests are presented in the main body).

The authors strongly emphasize the importance of there being no differences in body weight within animals of the same phenotype. This ensures that similar absolute amounts of glucose, insulin, or pyruvate were given to animals of the same phenotype before and after the institution of intermittent fasting. This is important not only because, at least for mice, smaller animals have been documented to be more insulin-sensitive, but also because it suggests that the I.F. regimen did not induce physiologically consequential loss of body fat; which would have resulted in an increased lean musculature-to-body weight ratio and an increased pancreatic Islet of Langerhans -cell-to-body weight ratio; during body weight-based, bolus-based testing, these anatomical alterations would effect improved blood glucose assimilation even if there were no histological, cellular, or macromolecular emendations due to the diets. While improved blood glucose regulation by any means would be worth reporting and investigating further for potential translatability, a mechanistic understanding of the results presented herein is abetted by this lack of dietary effect on body weight. Additionally, a non-weight loss diet that results in dramatically improved health would be more psychologically palatable to patients than one that focuses on, or results in, weight loss.

All measures of central tendency are arithmetic means, and all depictions of variation (error bars) represent standard deviations (S.D.).

II.The Home-Cage Assessment Rubric is contained within the Supplemental Information section.

SUPPLEMENTAL FIGURES

S1, related to Figure 2A. S2, related to Figure 2A.

S3, related to Figure 2B. S4, related to Figure 2B.

S9, related to Figure 3A. S10, related to Figure 3A.

S13, related to Figure 3C. S14, related to Figure 3C.

S5, related to Figure 2C. S6, related to Figure 2C.

S7, related to Figure 2D. S8, related to Figure 2D.

S11, related to Figure 3B. S12, related to Figure 3B.

S15, related to Figure 3D. S16, related to Figure 3D.

S17, related to Figure 5A. S18, related to Figure 5A.

S19, related to Figure 5B. S20, related to Figure 5B.

S25, related to Figure 6A. S26, related to Figure 6A.

S27, related to Figure 6B. S28, related to Figure 6B.

S29, related to Figure 6C. S30, related to Figure 6C.

S37, related to Figure 6G. S38, related to Figure 6G.

S21, related to Figure 5C. S22, related to Figure 5C.

S23, related to Figure 5D. S24, related to Figure 5D.

S31, related to Figure 6D. S32, related to Figure 6D.

S33, related to Figure 6E. S34, related to Figure 6E.

S35, related to Figure 6F. S36, related to Figure 6F.

S39, related to Figure 6H. S40, related to Figure 6H.

Supplemental Table I: Home-Cage Assessment Rubric

Condition / Rating / Description
Initial Posture / 1 / Sitting or standing normally, rearing or asleep
2 / Crouching over or lying low
3 / Slight sway while in standing position
4 / Excessive sway or head bobbing in standing position
5 / Flattened, limbs may be spread out
6 / Lying on side, limbs in air
Salivation / 1 / None
2 / Slight
3 / Severe
Lacrimation / 1 / None
2 / Slight
3 / Severe
Fur / 1 / Normal, silky and smooth
2 / Pilo-erection
3 / Over groomed
Vocalization / 0 / No, spontaneous vocals
1 / Yes, spontaneous vocals

1