Protein may cause obesity by interfering with brown fat

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Not all body fat is bad news. In fact, the so-called brown and beige fat fulfills important metabolic functions, producing energy and helping the body to adjust to cold temperatures.

New research finds that high levels of a certain protein may increase obesity by suppressing the energy-producing action of brown and beige fat.

New research suggests that targeting the Id1 protein may help to reverse obesity by increasing levels of brown fat and reducing white fat, which is commonly found on the belly.

Our bodies store energy in the form of fat. The fat, or adipose, tissue – which helps to regulate the body’s metabolism – is typically divided into two main types: white and brown. Additionally, a third type of fat can develop from white fat, as “beige” cells can form there when activated by certain stimuli.

White and brown fat have different functions. White fat mainly stores energy in the form of triglycerides – a type of fat commonly found in the blood, which may trigger conditions such as heart disease and diabetes if abnormally high. Brown fat, on the other hand, specializes in expending that energy by creating heat during exposure to cold temperatures, in a process known as thermogenesis.

There are also structural differences between these types of fat. Brown and beige fat have more mitochondria, which are also known as the “powerhouses” of the cell because they turn food into energy. White fat, on the other hand, has fewer mitochondria and blood vessels.

Brown and beige fat are considered “healthier” than white fat. Previous research has suggested that brown and beige fat reduce metabolic diseases and obesity in mice, and studies in humans have revealed a connection between leanness and these types of fat.

New research – published in the journal Diabetes – shows that high levels of a certain protein diminishes the positive, energy-producing effects of brown and beige fat.

The corresponding author of the study is Dr. Satya Ande, a molecular biologist at the Georgia Cancer Center and Medical College of Georgia at Augusta University.

The protein is called Id1, and previous research has connected it with prostate cancer.

In their study, Ande and colleagues genetically modified mice to produce excessive levels of Id1 in their fat cells.

They then fed these mice a high-fat diet, as well as a regular diet. They also fed a control group of normal mice the same diets.

The mice that overproduced Id1 gained significantly more weight than the control mice. They also gained more weight than their normal counterparts while on a regular diet.

The study revealed that high levels of Id1 bind to brown adipose tissue, suppressing its fat-burning action.

Specifically, in high amounts, Id1 inhibits the activity of the key transcription factor, PGC1 alpha. This transcription factor regulates thermogenesis by controlling the unique protein Ucp1, which, in turn, makes brown fat cells burn energy for heat more efficiently.

Additionally, the researchers found that Id1 inhibits another transcription factor, Ebf2, which usually helps white fat turn into beige. Ande and team also demonstrated that removing Id1 increases the expression of the beige gene and Ucp1 in the response of white fat to cold exposure.

Furthermore, removing the Id1 protein did not seem to suggest that it is needed for normal functioning – at least not in mice.

According to the researchers, the findings suggest that the Id1 protein is a risk factor for obesity and diabetes, and it could be a target for reversing these two conditions.

“If we can target Id1, we may able to prevent […] and ultimately reduce the risk of obesity and related disease.”

Dr. Satya Ande

For most of us, it becomes increasingly hard to produce brown fat as we age, which explains why we tend to gain weight more easily. Targeting Id1 at a molecular level, however, may help to increase brown fat, Ande adds.