1. Gene expression (fold-increase vs. untreated control) > 7-fold Insulin/Glucose axis-unrelated genes Insulin/Glucose axis-related genes a Supplemental Figure 1

2. b Fasting glucose (mg/dl) FASN/mRNA PPIA mRNA in OM adipose tissue Supplemental Figure 1

3. 3T3-L1 DNA FASN Adipocytes MCF-7 Day 0 MCF-7 Day 9 Control Metformin Tumor cells DNA FASN FASN up-regulation ADIPOCYTE MATURATION FASN down-regulation CELL GROWTH INHIBITION a Supplemental Figure 2

4. b AMPK INACTIVE EXERCISE CALORIE DEPRIVATION METFORMIN THIAZOLIDINEDIONES Other AMPK activators AMP ATP ? + + AMPK ACTIVE P P P P ACUTE EFFECT CHRONIC EFFECTS LOW-ENERGY STATUS FASN mRNA FASN promoter FASN gene transcription ACACA activity FASN mRNA translation mTOR TSC2TSC1 S6K1 4E-BP1 Protein synthesis initiation Supplemental Figure 2