The discovery of a new molecular pathway could help fight obesity, type 2 diabetes and cardiovascular disease.
Researchers at McGill University have been investigating a protein known as folliculin and how it regulates the activity of fat cells. They found that inhibiting the gene that produces folliculin in fat cells in mice led to cells burning fat, instead of storing it.
If a drug can be developed that stimulates this activity, it could help manage obesity and other metabolic disorders such as type 2 diabetes, which has a significant relationship with obesity, and cardiovascular disease.
This process is known as the ‘browning’ of fat cells. Brown fat burns energy to produce heat, and this keeps our temperature constant. White fat, on the other hand, stores energy, while beige fat can behave like brown fat when responding to certain stimuli such as exposure to cold, and researchers worldwide are exploring how white fat cells can be converted into energy-burning beige cells.
In this new study, McGill scientists bred mice to have fat cells that did not produce folliculin. This group of mice and a control group of normal mice were both fed a high-calorie diet over 14 weeks.
The control group gained weight quickly, but the folliculin-deficient mice remained slim. Moreover, the control group experienced elevated insulin and triglyceride levels; the folliculin-deficient mice did not.
The researchers discovered that the genetically modified mice were burning more fat, and had smaller white fat cells and less white fat tissue overall at the end of the trial. This also made them more capable of tolerating cold temperatures.
“These findings identify a key role of FLCN as a negative regulator of mitochondrial function and identify a novel molecular pathway involved in the browning of white adipocytes and the activity of brown fat,” said the authors.
Study author Vincent Giguère added: “Since that mechanism involves a class of proteins that can be targeted by drugs that are readily absorbed in the body, one implication is that a drug could be developed to stimulate the activity of beige/brown fat cells and thus help manage obesity and other metabolic disorders.”
The study appears in the journal Genes and Development.

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