Supplementary File 1

A. Mathematic model of Whi5 kinetics The major role of this mathematic model is to analytically derive the correlation between Cln3 and T G1 coupled by Whi5 phosphorylation under more general conditions without the assumption of saturation for any enzyme. In this section we simplified the phosphorylation of Whi5 by Cln3 as a single step process. From numerical simulation of Whi5 kinetics and phase diagram of Whi5 (fig. 1), we found that the major part of G1 is the process for the nuclear Whi5 to drop from Whi5 tot to Whi5 c. Here Whi5 c is defined as the corresponding value of Whi5 in phase diagram when Cln3 equals to Cln3 c , below which the positive feedback loop takes effect and greatly accelerate the Start transition. figure 1. (A) The phase diagram of Whi5. The red lines show stable state nuclear Whi5 values as a function of Cln3. If the nuclear Whi5 drops below Whi5 c , the switch is irreversibly flipped. (B) The nuclear Whi5 dynamics at Cln3=200. A and B are simulated by the ODE model (see section B). Since the Start transition itself is very quick, we neglected its time in the calculation of T G1 for simplicity. We also assume Cln3 concentration is constant through G1. Here we derived the correlation between T G1 and Cln3 based on these simplifications. The scheme of the model is shown in fig. 2A, and the equations are listed as follows: 5 5 5 p p p d Whi phos c Whi phos p f Whi phos dt


Nutritional challenge with a High Fat Diet
Eighteen-week-old WT, Pparα hep-/-, and Pparα -/mice were fed for two weeks with a HFD (D12492) or control diet (D12450J) obtained from Research Diet. Mice were killed at ZT8 (n=6 animals/genotype/group).

Blood and tissue samples
Prior to sacrifice, blood was collected from the submandibular vein with a lancet into EDTAcoated tubes (BD Microtainer, K2E tubes). Plasma was prepared by centrifugation (1500g, 10 min, 4°C) and stored at −80°C. Following euthanasia by cervical dislocation, organs were removed, weighed, dissected when necessary, and prepared for histological analysis, or snap-frozen in liquid nitrogen and stored at −80°C.
TGs, free cholesterol, and cholesterol esters were analysed by gas-liquid chromatography using a Focus Thermo Electron system with a Zebron-1 Phenomenex fused-silica capillary column (5 m, 0.32-mm i.d., 0.50-mm film thickness). Oven temperature was programmed to increase from 200 to 350°C at 5°C/min, and the carrier gas was hydrogen (0.5 bar). The injector and the detector temperatures were 315°C and 345°C, respectively.

Liver fatty acid analysis
To measure total hepatic fatty acid methyl ester (FAME) molecular species, lipids corresponding to an equivalent of 1 mg of liver were extracted in the presence of glyceryl triheptadecanoate (0.5 μg) as an internal standard. The lipid extract was transmethylated with 1 ml of BF3 in methanol (14% solution; Sigma-Aldrich) and 1 ml of hexane for 60 minutes at 100°C and evaporated to dryness, and the FAMEs were extracted with hexane/water (2:1). The organic phase was evaporated to dryness and dissolved in 50 μl ethyl acetate. A sample (1 μl) of total FAME was analyzed by gas-liquid chromatography (Clarus 600 Perkin Elmer system, with Famewax RESTEK fused silica capillary columns, 30-m×0.32-mm i.d., 0.25-μm film thickness). Oven temperature was programmed from 110°C to 220°C at a rate of 2°C per minute, and the carrier gas was hydrogen (7.25 psi). The injector and the detector were at 225°C and 245°C, respectively.

Transcriptomic analysis
A model was fitted using the limma lmFit function (1), and correction for multiple testing was applied using False Discovery Rate (Benjamini et al. 1995). Probes with an adjusted p value ≤0.05 were considered differentially expressed between conditions. Hierarchical clustering was applied to samples and differentially expressed probes using Pearson's correlation coefficient as distance and Ward's criterion for agglomeration. Gene Ontology (GO) Biological Process enrichment was evaluated using a conditional hypergeometric test (GOstats package,(3)). Functional annotation clustering of GO Biological Process were performed using DAVID Bioinformatics Resources 6.7 ((4,5)). Gene-gene interaction network were predicted using "Search Tool for the Retrieval of Interacting Genes" ((6) String V10).
(2) Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A practical and powerful Approach to multiple testing. Journal of the royal Statistical Society. Series B (methodological), Vol.57, No.1 (1995), 289-300.  Hepatic fatty acid profile is modified by fasting and sensitive to hepatocyte Pparα deficiency. Relative abundance of hepatic fatty acids in WT and Pparα hep-/mice fed or fasted for 24 hours was quantified by gas-liquid chromotography. Data are shown as mean ±SEM (n= 8 per group). *p≤0.05, **p≤0.01, ***p≤0.005.