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BACE1 Knockout Mice and BACE1 inhibition in Mouse models of obesity/diabetes

BACE1 Knockout Mice and BACE1 inhibition in Mouse models of obesity/diabetes. Stuart Irvine. Obesity & Type II Diabetes. The problem. http://www.dh.gov.uk/health/2012/04/obesityfacts/. Leptin. X. From the following article: Leptin and the regulation of body weight in mammals

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BACE1 Knockout Mice and BACE1 inhibition in Mouse models of obesity/diabetes

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  1. BACE1 Knockout Mice and BACE1 inhibition in Mouse models of obesity/diabetes Stuart Irvine

  2. Obesity & Type II Diabetes • The problem http://www.dh.gov.uk/health/2012/04/obesityfacts/

  3. Leptin X From the following article: Leptin and the regulation of body weight in mammals Jeffrey M. Friedman and Jeffrey L. Halaas Nature 395, 763-770(22 October 1998)

  4. Beta-secretase 1 (BACE1) and Mouse Models • BACE1 is a protease responsible for cleaving Amyloid precursor protein (APP) into Aβ. • Important in plaque formation in Alzheimer’s Disease

  5. BACE1 models and obesity • BACE 1 KO model1 • High fat diet • Lean phenotype • Low leptin levels in the blood • Leptin sensitive/Low leptin levels • Insulin sensitive (non-diabetic) • BACE1 inhibition • WT mice on a HF diet, with features of obesity, type II diabetes, leptin insensitivity etc • Using BACE1 inhibitor, mice will revert back to lean, leptin/insulin-sensitive animal • Weight lost is fat (not muscle) • Leptin levels drop too 1P Meakin et al. Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice. Biochem J. 2012 January 1; 441(Pt 1): 285–296.

  6. Objectives of my Project • How is knocking out BACE1/ inhibiting BACE1 producing a lean animal, even on a high fat diet? • Gene Expression Studies

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