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siRNA unrelated AdipoR1 AdipoR2

**. the muscle. 3 2 1 0. None Ad Osm A9 None Ad Osm A9 None Ad Osm A9. Ratio. Protein ( μ M) None Ad Osm A9 0.10 0.04 0.50. siRNA Unrelated. siRNA unrelated AdipoR1 AdipoR2. AdipoR1. AdipoR2. Ad.

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siRNA unrelated AdipoR1 AdipoR2

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  1. ** the muscle 3 2 1 0 None Ad Osm A9 None Ad Osm A9 None Ad Osm A9 Ratio Protein (μM) None Ad Osm A9 0.10 0.04 0.50 siRNA Unrelated siRNA unrelated AdipoR1 AdipoR2 AdipoR1 AdipoR2 Ad Osmotin Induces AMPK Activation In Murine C2C12 Myocytes Via Adiponectin Receptors Osmotin Mimics Adiponectin AMPK-P OSM AMPK Narasimhan et al, Mol Cell (2005) 17: 171-180

  2. Adiponectin Improves Mitochondrial Function In Human Muscle Cells Increase ATP production the muscle • Improved mitochondrial function • Increased mitochondrial number Increased fatty acid oxidation Increased expression PGC1α Increased glucose catabolism AMPK-P↑ Reduction of Blood glucose and fatty acids Adiponectin receptor Adiponectin Antidiabetic (Antidiabetic) A. E. Civitarese

  3. Osmotin induces Beta Oxidation activity (3h) 4.40 4.00 3.60 3.20 (umole/min/mg protein) βHAD Activity 2.80 2.40 2.00 1.60 1.20 0.80 control 1ug/ml 5ug/ml Fatty acid βHAD Acetyl CoA TCA cycle ATP Osmotin Promotes Fatty Acid Oxidation In Human Biopsy Muscle Cells A. E. Civitarese

  4. Osmotin Promotes Glucose Catabolism in Human Biopsy Muscle Cells Osmotin induces TCA Cycle activity Osmotin increases mitochondrial number 2.00 250 200 mtDNA/nucleargenome 1.60 150 (umole/min/mg protein) Citrate Synthase Activity 100 1.20 50 0 0.80 Control 1ug/ml 2.5ug/ml control 1ug/ml 2.5ug/ml TCA cycle Glucose mitochondria A. E. Civitarese

  5. Osmotin Promotes AMPK Activation And PGC1α Gene Expression in Human Biopsy Muscle Cells AMPK-P Total AMPK PGC1α β-actin Osmotin (µg/ml) 0 1 5 7.5 10 20 A. E. Civitarese

  6. Osmotin Improves Mitochondrial Function In Human Muscle Cells (Antidiabetic) the muscle Increase ATP production • Improved mitochondrial function • Increased mitochondrial number Increased lipid oxidation Increased expression PGC1α Increased glucose uptake AMPK-P↑ Reduction of Blood glucose and fatty acids Adiponectin receptor Osmotin Antidiabetic Osmotin Mimics Adiponectin

  7. Osmotin Improved Hyperglycemia In db/db Mice Relative Plasma Glucose Levels Test materials delivered by intraperitoneal injection 120 100 PBS Osmotin 80 60 0 15 30 60 120 min Osmotin Mimics Adiponectin Yamauchi et al., 2001, Nat Med 7:941-946 Yamauchi et al, unpublished data

  8. Plasma Adiponectin Levels Have Inverse Correlation With The Severity Of Colitis Stomach Colon Severity of Colitis↑ Plasma Adiponectin↓ Small intestine ↑ ↓ Rectum Crohn’s disease (colitis, usually of small intestine), Diarrhea, Abdominal pain Weight loss, Anemia, Inflammation

  9. Osmotin Treatment Reduces Weight Loss And Anemia Associated With Induced Colitis In Mice Body Weight Gain Hematocrit 50 * 40 20 Percent 30 10 * % body weight gain 20 0 10 0 -10 Water DSS+ SAL DSS+ OSM Water DSS+ SAL DSS+ OSM colitis colitis R. Arsenescu

  10. 200 150 100 pg/ml pg/ml 100 50 0 DSS+ SAL DSS+ OSM WATER 0 WATER DSS+ SAL DSS+ OSM Osmotin Treatment Reduces Inflammation Associated With Induced Colitis In Mice Plasma IL-10 (Anti-inflammatory cytokine) Plasma IL-1β (Pro-inflammatory cytokine) * colitis colitis R. Arsenescu

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