Protein-based nutrient sensor could provoke calorie burning in obesity battle: Study

By Will Chu

- Last updated on GMT

Nutrient levels are considered a key regulator of fat browning and a treatment that can increase the number of brown fat-like cells to burn more calories may be possible. (© iStock.com)
Nutrient levels are considered a key regulator of fat browning and a treatment that can increase the number of brown fat-like cells to burn more calories may be possible. (© iStock.com)

Related tags Adipose tissue

A group of proteins called mTORC1 that sense nutrient levels could hold the key to providing a viable method to target metabolic disorders such as obesity.

Nutrient levels are considered a key regulator of fat browning and a treatment that can increase the number of brown fat-like cells to burn more calories and would give hope to those that struggle to lose weight from exercise alone.

The research focuses on mTORC1, a collection of proteins that regulates cell growth and metabolism in response to environmental cues such as growth factors and nutrients.

The team believe they have discovered a new step in the pathway by which the neurotransmitter noradrenaline promotes fat browning.

Previous research had shown noradrenaline activates the enzyme protein kinase A​ (PKA), which this study shows activates mTORC1.

Brown good, white bad

insulin cell
The amount of detectable brown fat cells is significantly correlated with reduced percent body fat and circulating triglycerides.(© iStock.com)

Dr Sheila Collins from the Sanford-Burnham Prebys Medical Discovery Institute, led her team to these findings through experiments using mice models.

These mice had an mTORC1 impairment, rendering them unable to produce brown fat-like cells in white fat deposits.

The team found that the browning of white adipose cells in these mice required the activation of mTORC1 and an enzyme S6K1 through a specialised mechanism.

Specifically, both mTOR and the mTORC1 component RAPTOR can be altered structually by PKA, and interference with RAPTOR’s alteration by PKA prevented activation of S6K1.

These findings illustrate the existence of a new signalling pathway from PKA to mTORC1 and its requirement for the sympathetic nervous system–driven (SNS-driven) recruitment and expansion of the brown fat cells in white fat tissue.

"This result came as a surprise because we knew that mTORC1 is a key player in stimulating growth in many tissues, including white fat,"​ said Collins.

"Fat browning is thought to be an opposing process, so the fact that it requires the same protein complex is big news."

Brown fat consumes energy producing heat, and scientists believe this a way the body stays warm and survives cold weather.

Adults with higher-than-average amounts of brown fat are more likely to maintain a healthy weight and are less likely to develop insulin resistance.

In contrast, white fat acts as a thermal insulator that protects internal organs. An excess of white fat is associated with metabolic disease, as well as an increased risk of certain cancers.

The proportion of brown fat-like cells in white fat deposits increases upon prolonged exposure to cold temperatures, which triggers the release of noradrenaline.

"Fat regulation isn't black and white - our results help fill in the colour in the picture. Imagine mTORC1 is a machine with multiple capabilities, like a printer/copier/scanner,”​ added Collins.

“Energy-storage signalling pushes one set of buttons and gets one outcome (fat storage), while PKA pushes another set to get a different outcome (conversion to brown fat).”

Similar studies

weight_obesity_weightloss
Studies show that the increase in these beige adipocytes closely correlates with resistance to obesity, (© iStock.com)

Studies​ using mouse models show that the increase in these brown adipocytes closely correlates with resistance to obesity, and in humans, the amount of detectable brown fat cells is significantly correlated with reduced percent body fat and circulating triglycerides​.

In explaining their findings the researchers were sure that a signalling pathway from PKA to mTORC1 activation existed via the structural alteration of mTOR and RAPTOR.

“Given these findings and the expression of mTOR and PKA in many cell types, we speculate that this PKA-mTORC1 pathway may have broader significance by regulating a variety of cell signalling events in other tissues,”​ the study said.  

“Our studies illustrate that an inherently catabolic (breaking down) process of energy expenditure in adipose tissue utilises what is most commonly considered to be the molecular driver of growth and anabolic metabolism. This deserves fresh appraisal.”

Source: Journal of Clinical Investigation

Published online ahead of print, doi.org/10.1172/JCI83532

“Activation of mTORC1 is essential for β-adrenergic stimulation of adipose browning.”

Authors: Dianxin Liu, Marica Bordicchia, Chaoying Zhang, Huafeng Fang, Wan Wei, Jian-Liang Li, Adilson Guilherme, Kalyani Guntur, Michael P. Czech, and Sheila Collins

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