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Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet

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Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet. / Jamieson, P. M.; Cleasby, M. E.; Kuperman, Y.; Morton, N. M.; Kelly, P. A. T.; Brownstein, D. G.; Mustard, K. J.; Vaughan, J. M.; Carter, R. N.; Hahn, C. N.; Hardie, D. G.; Seckl, J. R.; Chen, A.; Vale, W. W.

In: Diabetologia, Vol. 54, No. 9, 2011, p. 2392-2403.

Research output: Contribution to journalArticle

Harvard

Jamieson, PM, Cleasby, ME, Kuperman, Y, Morton, NM, Kelly, PAT, Brownstein, DG, Mustard, KJ, Vaughan, JM, Carter, RN, Hahn, CN, Hardie, DG, Seckl, JR, Chen, A & Vale, WW 2011, 'Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet' Diabetologia, vol 54, no. 9, pp. 2392-2403., 10.1007/s00125-011-2205-6

APA

Jamieson, P. M., Cleasby, M. E., Kuperman, Y., Morton, N. M., Kelly, P. A. T., Brownstein, D. G., ... Vale, W. W. (2011). Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet. Diabetologia, 54(9), 2392-2403. 10.1007/s00125-011-2205-6

Vancouver

Jamieson PM, Cleasby ME, Kuperman Y, Morton NM, Kelly PAT, Brownstein DG et al. Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet. Diabetologia. 2011;54(9):2392-2403. Available from: 10.1007/s00125-011-2205-6

Author

Jamieson, P. M.; Cleasby, M. E.; Kuperman, Y.; Morton, N. M.; Kelly, P. A. T.; Brownstein, D. G.; Mustard, K. J.; Vaughan, J. M.; Carter, R. N.; Hahn, C. N.; Hardie, D. G.; Seckl, J. R.; Chen, A.; Vale, W. W. / Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet.

In: Diabetologia, Vol. 54, No. 9, 2011, p. 2392-2403.

Research output: Contribution to journalArticle

Bibtex - Download

@article{5fdffe93e25e4ca2badae4dac19e2394,
title = "Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet",
keywords = "CRFR2, Energy balance, Glucose uptake, IGF-1, Obesity, Skeletal muscle, Transgenic mice, Urocortin 3, GROWTH-FACTOR-I, CORTICOTROPIN-RELEASING-FACTOR, IMPROVES GLYCEMIC CONTROL, SKELETAL-MUSCLE MASS, INSULIN-RESISTANCE, 11-BETA-HYDROXYSTEROID DEHYDROGENASE, GLUCOSE-UTILIZATION, ENERGY HOMEOSTASIS, DIABETES-MELLITUS, TUMOR-GROWTH",
author = "Jamieson, {P. M.} and Cleasby, {M. E.} and Y. Kuperman and Morton, {N. M.} and Kelly, {P. A. T.} and Brownstein, {D. G.} and Mustard, {K. J.} and Vaughan, {J. M.} and Carter, {R. N.} and Hahn, {C. N.} and Hardie, {D. G.} and Seckl, {J. R.} and A. Chen and Vale, {W. W.}",
year = "2011",
doi = "10.1007/s00125-011-2205-6",
volume = "54",
number = "9",
pages = "2392--2403",
journal = "Diabetologia",
issn = "0012-186X",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet

A1 - Jamieson,P. M.

A1 - Cleasby,M. E.

A1 - Kuperman,Y.

A1 - Morton,N. M.

A1 - Kelly,P. A. T.

A1 - Brownstein,D. G.

A1 - Mustard,K. J.

A1 - Vaughan,J. M.

A1 - Carter,R. N.

A1 - Hahn,C. N.

A1 - Hardie,D. G.

A1 - Seckl,J. R.

A1 - Chen,A.

A1 - Vale,W. W.

AU - Jamieson,P. M.

AU - Cleasby,M. E.

AU - Kuperman,Y.

AU - Morton,N. M.

AU - Kelly,P. A. T.

AU - Brownstein,D. G.

AU - Mustard,K. J.

AU - Vaughan,J. M.

AU - Carter,R. N.

AU - Hahn,C. N.

AU - Hardie,D. G.

AU - Seckl,J. R.

AU - Chen,A.

AU - Vale,W. W.

PY - 2011

Y1 - 2011

N2 - <p>Urocortins are the endogenous ligands for the corticotropin-releasing factor receptor type 2 (CRFR2), which is implicated in regulating energy balance and/or glucose metabolism. We determined the effects of chronic CRFR2 activation on metabolism in vivo, by generating and phenotyping transgenic mice overproducing the specific CRFR2 ligand urocortin 3.</p><p>Body composition, glucose metabolism, insulin sensitivity, energy efficiency and expression of key metabolic genes were assessed in adult male urocortin 3 transgenic mice (Ucn3 (+) ) under control conditions and following an obesogenic high-fat diet (HFD) challenge.</p><p>Ucn3 (+) mice had increased skeletal muscle mass with myocyte hypertrophy. Accelerated peripheral glucose disposal, increased respiratory exchange ratio and hypoglycaemia on fasting demonstrated increased carbohydrate metabolism. Insulin tolerance and indices of insulin-stimulated signalling were unchanged, indicating these effects were not mediated by increased insulin sensitivity. Expression of the transgene in Crfr2 (also known as Crhr2)-null mice negated key aspects of the Ucn3 (+) phenotype. Ucn3 (+) mice were protected from the HFD-induced hyperglycaemia and increased adiposity seen in control mice despite consuming more energy. Expression of uncoupling proteins 2 and 3 was higher in Ucn3 (+) muscle, suggesting increased catabolic processes. IGF-1 abundance was upregulated in Ucn3 (+) muscle, providing a potential paracrine mechanism in which urocortin 3 acts upon CRFR2 to link the altered metabolism and muscular hypertrophy observed.</p><p>Urocortin 3 acting on CRFR2 in skeletal muscle of Ucn3 (+) mice results in a novel metabolically favourable phenotype, with lean body composition and protection against diet-induced obesity and hyperglycaemia. Urocortins and CRFR2 may be of interest as potential therapeutic targets for obesity.</p>

AB - <p>Urocortins are the endogenous ligands for the corticotropin-releasing factor receptor type 2 (CRFR2), which is implicated in regulating energy balance and/or glucose metabolism. We determined the effects of chronic CRFR2 activation on metabolism in vivo, by generating and phenotyping transgenic mice overproducing the specific CRFR2 ligand urocortin 3.</p><p>Body composition, glucose metabolism, insulin sensitivity, energy efficiency and expression of key metabolic genes were assessed in adult male urocortin 3 transgenic mice (Ucn3 (+) ) under control conditions and following an obesogenic high-fat diet (HFD) challenge.</p><p>Ucn3 (+) mice had increased skeletal muscle mass with myocyte hypertrophy. Accelerated peripheral glucose disposal, increased respiratory exchange ratio and hypoglycaemia on fasting demonstrated increased carbohydrate metabolism. Insulin tolerance and indices of insulin-stimulated signalling were unchanged, indicating these effects were not mediated by increased insulin sensitivity. Expression of the transgene in Crfr2 (also known as Crhr2)-null mice negated key aspects of the Ucn3 (+) phenotype. Ucn3 (+) mice were protected from the HFD-induced hyperglycaemia and increased adiposity seen in control mice despite consuming more energy. Expression of uncoupling proteins 2 and 3 was higher in Ucn3 (+) muscle, suggesting increased catabolic processes. IGF-1 abundance was upregulated in Ucn3 (+) muscle, providing a potential paracrine mechanism in which urocortin 3 acts upon CRFR2 to link the altered metabolism and muscular hypertrophy observed.</p><p>Urocortin 3 acting on CRFR2 in skeletal muscle of Ucn3 (+) mice results in a novel metabolically favourable phenotype, with lean body composition and protection against diet-induced obesity and hyperglycaemia. Urocortins and CRFR2 may be of interest as potential therapeutic targets for obesity.</p>

KW - CRFR2

KW - Energy balance

KW - Glucose uptake

KW - IGF-1

KW - Obesity

KW - Skeletal muscle

KW - Transgenic mice

KW - Urocortin 3

KW - GROWTH-FACTOR-I

KW - CORTICOTROPIN-RELEASING-FACTOR

KW - IMPROVES GLYCEMIC CONTROL

KW - SKELETAL-MUSCLE MASS

KW - INSULIN-RESISTANCE

KW - 11-BETA-HYDROXYSTEROID DEHYDROGENASE

KW - GLUCOSE-UTILIZATION

KW - ENERGY HOMEOSTASIS

KW - DIABETES-MELLITUS

KW - TUMOR-GROWTH

U2 - 10.1007/s00125-011-2205-6

DO - 10.1007/s00125-011-2205-6

M1 - Article

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 9

VL - 54

SP - 2392

EP - 2403

ER -

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