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AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance.


ABSTRACT: The AMP-activated protein kinase (AMPK) is an alphabetagamma heterotrimer that regulates appetite and fuel metabolism. We have generated AMPK beta1(-/-) mice on a C57Bl/6 background that are viable, fertile, survived greater than 2 years, and display no visible brain developmental defects. These mice have a 90% reduction in hepatic AMPK activity due to loss of the catalytic alpha subunits, with modest reductions of activity detected in the hypothalamus and white adipose tissue and no change in skeletal muscle or heart. On a low fat or an obesity-inducing high fat diet, beta1(-/-) mice had reduced food intake, reduced adiposity, and reduced total body mass. Metabolic rate, physical activity, adipose tissue lipolysis, and lipogenesis were similar to wild type littermates. The reduced appetite and body mass of beta1(-/-) mice were associated with protection from high fat diet-induced hyperinsulinemia, hepatic steatosis, and insulin resistance. We demonstrate that the loss of beta1 reduces food intake and protects against the deleterious effects of an obesity-inducing diet.

SUBMITTER: Dzamko N 

PROVIDER: S-EPMC2804155 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance.

Dzamko Nicolas N   van Denderen Bryce J W BJ   Hevener Andrea L AL   Jørgensen Sebastian Beck SB   Honeyman Jane J   Galic Sandra S   Chen Zhi-Ping ZP   Watt Matthew J MJ   Campbell Duncan J DJ   Steinberg Gregory R GR   Kemp Bruce E BE  

The Journal of biological chemistry 20091105 1


The AMP-activated protein kinase (AMPK) is an alphabetagamma heterotrimer that regulates appetite and fuel metabolism. We have generated AMPK beta1(-/-) mice on a C57Bl/6 background that are viable, fertile, survived greater than 2 years, and display no visible brain developmental defects. These mice have a 90% reduction in hepatic AMPK activity due to loss of the catalytic alpha subunits, with modest reductions of activity detected in the hypothalamus and white adipose tissue and no change in s  ...[more]

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