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

Nicolas Dzamko, Bryce J W van Denderen, Andrea L Hevener, Sebastian B Jorgensen, Jane Honeyman, Sandra Galic, Zhi -Ping Chen, Matthew James Watt, Duncan J Campbell, Gregory R Steinberg, Bruce E Kemp

Research output: Contribution to journalArticleResearchpeer-review

115 Citations (Scopus)

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 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 was associated with protection from high-fat diet induced hyperinsulinemia, hepatic steatosis and insulin resistance. We demonstrate that loss of beta1 reduces food intake and protects against the deleterious effects of an obesity-inducing diet.
Original languageEnglish
Pages (from-to)115 - 122
Number of pages8
JournalThe Journal of Biological Chemistry
Volume285
Issue number1
DOIs
Publication statusPublished - 2010

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