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Published on: May 16, 2021
AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance
Nicolas Dzamko1, Bryce J W van Denderen, Andrea L Hevener
1Department of Medicine, St Vincent's Institute of Medical Research, University of Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.
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.
Insights
AMP-activated protein kinase (AMPK) beta1 knockout mice exhibit reduced appetite and body mass. This AMPK deficiency protects against diet-induced obesity, insulin resistance, and hepatic steatosis.
Area of Science:
- Metabolic regulation
- Obesity research
- Biochemistry
Background:
- AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis and fuel metabolism.
- AMPK functions as an alpha-beta-gamma heterotrimer, with diverse roles in appetite and metabolic control.
Purpose of the Study:
- To investigate the physiological role of the AMPK beta1 subunit in vivo.
- To determine the impact of beta1 subunit deficiency on appetite, body mass, and diet-induced metabolic dysfunction.
Main Methods:
- Generation of AMPK beta1 knockout (beta1(-/-)) mice on a C57Bl/6 background.
- Assessment of AMPK activity in various tissues (liver, hypothalamus, white adipose tissue, skeletal muscle, heart).
- Evaluation of metabolic parameters, including food intake, body mass, adiposity, metabolic rate, physical activity, and diet-induced insulin resistance and hepatic steatosis.
Main Results:
- Beta1(-/-) mice were viable, fertile, and exhibited no overt developmental defects.
- A 90% reduction in hepatic AMPK activity was observed in beta1(-/-) mice, with modest reductions in the hypothalamus and white adipose tissue.
- Beta1(-/-) mice showed reduced food intake, adiposity, and total body mass on both low-fat and high-fat diets, with protection from diet-induced hyperinsulinemia, hepatic steatosis, and insulin resistance.
Conclusions:
- Loss of the AMPK beta1 subunit significantly reduces food intake and body mass.
- AMPK beta1 deficiency confers protection against the adverse metabolic consequences of a high-fat diet, highlighting its critical role in regulating appetite and preventing obesity-related diseases.
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