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Cerenkov Luminescence Imaging of Interscapular Brown Adipose Tissue
Published on: October 7, 2014
Pten positively regulates brown adipose function, energy expenditure, and longevity
Ana Ortega-Molina1, Alejo Efeyan, Elena Lopez-Guadamillas
1Tumor Suppression Group, Spanish National Cancer Research Center (CNIO), Madrid E28029, Spain.
Cell Metabolism
|March 13, 2012
Summary
Mice with extra Pten genes live longer and burn more energy by activating brown fat. This suggests Pten promotes energy expenditure, potentially reducing metabolic damage and extending lifespan.
Area of Science:
- Cellular and Molecular Biology
- Metabolism and Aging Research
- Genetics and Epigenetics
Background:
- The PI3K/Akt/Foxo pathway regulates aging in simpler organisms.
- Extending this pathway's study to mammals is crucial for understanding aging and metabolic diseases.
- Pten plays a known role in cellular processes, but its systemic effects on aging and metabolism require further investigation.
Purpose of the Study:
- To investigate the role of Pten in mammalian aging and metabolism.
- To determine if enhanced Pten activity impacts energy expenditure and metabolic health.
- To explore the mechanisms by which Pten influences brown adipose tissue (BAT) function.
Main Methods:
- Utilized Pten(tg) transgenic mice with extra Pten copies.
- Assessed lifespan, cancer incidence, energy expenditure, and metabolic pathologies.
- Analyzed brown adipose tissue (BAT) activity, including Ucp1 expression.
- Investigated the effects of a PI3K inhibitor on energy expenditure and BAT.
- Examined Pten(tg) fibroblast differentiation into brown adipocytes in vitro and in vivo.
Main Results:
- Pten(tg) mice exhibited extended lifespan, independent of cancer reduction.
- These mice showed increased energy expenditure and protection from metabolic diseases.
- Hyperactive BAT with elevated uncoupling protein 1 (Ucp1) was observed in Pten(tg) mice.
- Ucp1 was identified as a target of Foxo1, a downstream effector in the Pten pathway.
- PI3K inhibition mimicked Pten(tg) effects, increasing energy expenditure and activating BAT.
- Pten(tg) fibroblasts demonstrated enhanced formation of brown adipose tissue.
Conclusions:
- Pten plays a significant role in promoting energy expenditure and activating brown adipose tissue in mammals.
- This Pten-mediated activation of BAT leads to increased energy expenditure, reduced nutrient storage, and potentially mitigates associated damage.
- The findings suggest a novel mechanism linking Pten to metabolic regulation and lifespan extension, offering potential therapeutic targets for metabolic disorders and aging.
![Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62460.jpg&w=3840&q=50)
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