<p> Metabolic effects of FGF21 in DIO mice</p><p>Supplemental Figure 1. The expression of genes involved in thermogenesis, fatty acid oxidation and FGF21 signaling. Mice were treated with vehicle or recombinant murine FGF21 i.p. at doses of 0 (vehicle), 0.1, 1, or 10 mg/kg/day. An additional group of DIO mice was treated with rosiglitazone formulated in the HFD to provide a dose of approximately 4 mg/kg/day. RNA was prepared from various tissues after six weeks of treatment. The expression levels of mRNA were measured using real-time quantitative PCR (TaqMan). (A) The effects of recombinant FGF21 on uncoupling protein expression in brown adipose tissue (BAT). UCP 1 and 2: Uncoupling protein 1 and 2; (B) The effects of recombinant FGF21 on expression of genes involved in hepatic fatty acid oxidation. PPAR: Peroxisome proliferator – activated receptor alpha; CPT1: Carnitine palmitoyl transferase; ACS1: Acetyl – coenzyme A synthetase 1; LCAD: Long chain acyl – coenzyme A dehydrogenase; 3-OH-AD: 3 – hydroxyacyl – CoA dehydrogenase, ACOX: Acyl – coenzyme A oxidase. (B) The relative mRNA expression levels of β-klotho in liver, adipose tissues, skeletal muscle of mice fed SD or HDF. Data represent fold change relative to the levels in liver of SD-fed mice. WAT: white adipose tissue; BAT: brown adipose tissue.</p><p>1 Metabolic effects of FGF21 in DIO mice</p><p>Supplemental Table 1</p><p>Metabolic parameters during basal (12 h fast) and hyperinsulinemic-euglycemic clamp periods in mice chronically treated with muFGF21. Basal Clamp Body Insulin Glucose Insulin N Glucose (mg/dL) weight (g) (pM) (mg/dL) (pM) PBS 10 25  0 146  9 36  3 134  4 97  5 SD muFGF21 10 mg/kg 8 23  1* 143  9 32  4 132  6 84  7 PBS 12 43  1† 190  10‡ 139  41§ 170  11* 490  32† HFD muFGF21 0.1 mg/kg 12 43  1 151  7* 115  19 137  7║ 376  27║ muFGF21 10 mg/kg 12 35  1¶ 125  3¶ 72  17 129  7* 239  24¶ All data represent means  SEM. ║ P < 0.05, * P < 0.01, ¶ P < 0.001 vs. diet-matched PBS treated mice; § P < 0.05, ‡ P < 0.01, † P < 0.001 vs. SD-fed vehicle-treated mice.</p><p>2</p>