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Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

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Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice. / Meakin, Paul J.; Harper, Alex J.; Hamilton, D. Lee; Gallagher, Jennifer; McNeilly, Alison D.; Burgess, Laura A.; Vaanholt, Lobke M.; Bannon, Kirsten A.; Latcham, Judy; Hussain, Ishrut; Speakman, John R.; Howlett, David R.; Ashford, Michael L. J. (Lead / Corresponding author).

In: Biochemical Journal, Vol. 441, No. 1, 01.01.2012, p. 285-296.

Research output: Contribution to journalArticle

Harvard

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, vol 441, no. 1, pp. 285-296., 10.1042/BJ20110512

APA

Meakin, P. J., Harper, A. J., Hamilton, D. L., Gallagher, J., McNeilly, A. D., Burgess, L. A., ... Ashford, M. L. J. (2012). Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice. Biochemical Journal, 441(1), 285-296. 10.1042/BJ20110512

Vancouver

Meakin PJ, Harper AJ, Hamilton DL, Gallagher J, McNeilly AD, Burgess LA et al. Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice. Biochemical Journal. 2012 Jan 1;441(1):285-296. Available from: 10.1042/BJ20110512

Author

Meakin, Paul J.; Harper, Alex J.; Hamilton, D. Lee; Gallagher, Jennifer; McNeilly, Alison D.; Burgess, Laura A.; Vaanholt, Lobke M.; Bannon, Kirsten A.; Latcham, Judy; Hussain, Ishrut; Speakman, John R.; Howlett, David R.; Ashford, Michael L. J. (Lead / Corresponding author) / Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice.

In: Biochemical Journal, Vol. 441, No. 1, 01.01.2012, p. 285-296.

Research output: Contribution to journalArticle

Bibtex - Download

@article{835ed668559a429ba8f9847767cdb7b6,
title = "Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice",
keywords = "beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), glucose uptake, insulin sensitivity, liver, skeletal muscle, uncoupling protein (UCP), AMYLOID PRECURSOR PROTEIN, GROWTH-FACTOR EXPRESSION, BETA-SECRETASE ACTIVITY, BROWN ADIPOSE-TISSUE, HIGH-FAT-DIET, ALZHEIMERS-DISEASE, UNCOUPLING PROTEIN-3, KNOCKOUT MICE, FOOD-INTAKE, RESISTANCE",
author = "Meakin, {Paul J.} and Harper, {Alex J.} and Hamilton, {D. Lee} and Jennifer Gallagher and McNeilly, {Alison D.} and Burgess, {Laura A.} and Vaanholt, {Lobke M.} and Bannon, {Kirsten A.} and Judy Latcham and Ishrut Hussain and Speakman, {John R.} and Howlett, {David R.} and Ashford, {Michael L. J.}",
year = "2012",
doi = "10.1042/BJ20110512",
volume = "441",
number = "1",
pages = "285--296",
journal = "Biochemical Journal",
issn = "0264-6021",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

A1 - Meakin,Paul J.

A1 - Harper,Alex J.

A1 - Hamilton,D. Lee

A1 - Gallagher,Jennifer

A1 - McNeilly,Alison D.

A1 - Burgess,Laura A.

A1 - Vaanholt,Lobke M.

A1 - Bannon,Kirsten A.

A1 - Latcham,Judy

A1 - Hussain,Ishrut

A1 - Speakman,John R.

A1 - Howlett,David R.

A1 - Ashford,Michael L. J.

AU - Meakin,Paul J.

AU - Harper,Alex J.

AU - Hamilton,D. Lee

AU - Gallagher,Jennifer

AU - McNeilly,Alison D.

AU - Burgess,Laura A.

AU - Vaanholt,Lobke M.

AU - Bannon,Kirsten A.

AU - Latcham,Judy

AU - Hussain,Ishrut

AU - Speakman,John R.

AU - Howlett,David R.

AU - Ashford,Michael L. J.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - <p>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.</p>

AB - <p>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.</p>

KW - beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1)

KW - glucose uptake

KW - insulin sensitivity

KW - liver

KW - skeletal muscle

KW - uncoupling protein (UCP)

KW - AMYLOID PRECURSOR PROTEIN

KW - GROWTH-FACTOR EXPRESSION

KW - BETA-SECRETASE ACTIVITY

KW - BROWN ADIPOSE-TISSUE

KW - HIGH-FAT-DIET

KW - ALZHEIMERS-DISEASE

KW - UNCOUPLING PROTEIN-3

KW - KNOCKOUT MICE

KW - FOOD-INTAKE

KW - RESISTANCE

UR - http://ukpmc.ac.uk/articles/PMC3242510

UR - http://www.scopus.com/inward/record.url?scp=84055223593&partnerID=8YFLogxK

U2 - 10.1042/BJ20110512

DO - 10.1042/BJ20110512

M1 - Article

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

VL - 441

SP - 285

EP - 296

ER -

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