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UCSD researcher finds new mechanism for fat cell energy expenditure

UCSD Health
Posted at 10:43 AM, Oct 27, 2021
and last updated 2021-10-27 13:43:51-04

SAN DIEGO (CNS) — A team of researchers led by senior author Alan Saltiel, director of the Institute for Diabetes and Metabolic Health at UC San Diego School of Medicine, published a study Wednesday that describes how a previously unknown cellular pathway regulates energy and heat in obesity.

The discovery of the metabolic pathway for stored sugars, published online in Nature, can help explain how cellular energy is produced and expended in obesity, which could advance therapeutic potential.

A healthy human carries two different kinds of fat tissue -- white and brown -- the researchers wrote. The white fat cells are essentially containers of energy stored in a large oily droplet. Brown fat cells are more complex and contain multiple, smaller droplets that include mitochondria -- the powerhouse of cells that give the brown fat cells their color and convert the fat droplets into heat and energy.

Additionally, some people have "beige" fat cells, brown-like cells residing within white fat that can be activated to burn energy.

According to the researchers, in recent years, there has been considerable effort to find ways to increase brown or beige fat cell activity to burn energy and generate heat as a means to treat obesity, type 2 diabetes, and other conditions.

However, the therapeutic potential of brown fat -- and perhaps beige fat cells -- was limited by the complexity of the processes involved.

The human body breaks down carbohydrates into a type of sugar called glucose, the main source of fuel for cells. Extra glucose is packaged and stored as glycogen in the liver and skeletal muscle cells, where it can be extracted and quickly used for sudden energy needs or to maintain blood sugar levels, the researchers wrote.

The researchers discovered that glycogen does more than store energy in fat cells. It also provides a signal that produces a major shift in how energy is handled.

In this discovery, Saltiel and his fellow researchers report that the browning of fat cells depends on their ability to both make and use glycogen. The turnover of glycogen sends a signal that it is safe for the cell to "uncouple" the production of a molecule that provides the energy that fuels most cellular processes.

"Uncoupling is a way to generate heat, and in the process help balance energy," Saltiel said.

"This pathway thus ensures that only the fat cells with enough energy stores to fuel the generation of heat are allowed to do so."

Glycogen regulates and promotes fat metabolism: the higher the levels, the more energy and fat burned with resulting weight loss in obese mice. In humans, the genes involved in these complex processes were found to be lower in patients who were obese or prone to weight gain, suggesting that the glycogen pathway is needed in fat cells to burn off excess weight.

The findings, the authors write, suggest that modulating glycogen metabolism in fat cells might provide "new approaches for weight loss and overall improvement in metabolic health."