|Appears in Collections:||Faculty of Health Sciences and Sport Journal Articles|
|Peer Review Status:||Refereed|
|Title:||Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice|
|Author(s):||Meakin, Paul J|
Harper, Alex J
Hamilton, David Lee
McNeilly, Alison D
Burgess, Laura A
Vaanholt, Lobke M
Bannon, Kirsten A
Speakman, John R
Howlett, David R
Ashford, Michael L J
|Keywords:||beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1)|
uncoupling protein (UCP)
|Citation:||Meakin PJ, Harper AJ, Hamilton DL, Gallagher J, McNeilly AD, Burgess LA, Vaanholt LM, Bannon KA, Latcham J, Hussain I, Speakman JR, Howlett DR & Ashford MLJ (2012) Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice, Biochemical Journal, 441 (1), pp. 285-296.|
|Abstract:||Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1-/- mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1-/- mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes.|
|Rights:||The publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.|
|Hamilton_2012_Reduction_in_BACE1.pdf||1.21 MB||Adobe PDF||Under Permanent Embargo Request a copy|
Note: If any of the files in this item are currently embargoed, you can request a copy directly from the author by clicking the padlock icon above. However, this facility is dependent on the depositor still being contactable at their original email address.
This item is protected by original copyright
Items in the Repository are protected by copyright, with all rights reserved, unless otherwise indicated.
If you believe that any material held in STORRE infringes copyright, please contact firstname.lastname@example.org providing details and we will remove the Work from public display in STORRE and investigate your claim.