By changing the expression of a gene that affects body weight regulation and turns “bad” white fat into brown “good” fat, US scientists believe they may have found a way to help the body burn calories instead of storing them, opening the door to better treatments for obesity.

Lead researcher Dr Sheng Bi, an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues were researching appetite regulation in rats when they made their discovery.

They reported their findings in a study published this week in the journal Cell Metabolism.

Bi told the press:

“If we could get the human body to turn ‘bad fat’ into ‘good fat’ that burns calories instead of storing them, we could add a serious new tool to tackle the obesity epidemic in the United States.”

When we are born we have lots of brown fat cells, which is considered a “good fat” because it helps us burn energy as each brown fat cell comprises many small droplets of lipid, each with its own power source to produce heat. This property helps babies keep warm.

But and as we age we lose our calorie-burning brown fat, and we accumulate more and white fat, mostly around the waistline and on the hips. Unlike brown fat, white fat stores calories. White fat cells have one single droplet of lipid.

Bi and colleagues were investigating the properties of white and brown fat, in relation to an appetite-stimulating protein called hypothalamic neuropeptide Y (NPY), which is already known to be involved in the control of energy balance, but before this study, little was known about its other physiological effects.

NPY operates in the hypothalamus, a part of the brain that helps regulate thirst, hunger, body temperature, water balance and blood pressure. The hypothalamus lies deep inside the brain, just above the brain stem, and contains many small nuclei with different functions.

Using laboratory rats, Bi and colleagues investigated the role of NPY in one of these nuclei, the dorsomedial hypothalamus (DMH), and discovered that silencing the expression of DMH NPY:

  • Changes body weight regulation.
  • Encourages the production of brown fat cells in white fat deposits.
  • Increases energy expenditure and heat generation (cold-induced thermogenesis).
  • Improves glucose stability and increases insulin sensitivity.

For the study, Bi and colleagues used two groups of rats. They treated one group with a virus to silence NPY expression, and left the other group untreated to act as controls.

After five weeks on the same regular diet, the treated group weighed less that the control group, suggesting that suppression of NPY leads to reduced eating.

After that stage, they split each of the two groups into two so they had four groups: two treated and two untreated. They took one of the treated groups and one of the control groups and fed them a regular diet, and took the other treated and untreated group and fed them a high-fat diet.

After 11 weeks they weighed them again and found of the two regular diet groups, the treated group (with the silenced NPY) weighed less than the control group.

And while the two groups on the high fat diet put on weight, the rats with silenced NPY gained less weight than the control rats, who gained so much weight they ended up obese.

These results were no surprise to the researchers, since they already believed that silencing NPY would suppress desire to eat and result in less weight gain, regardless of diet.

But what did surprise them was what they found when they examined the fat deposits in the groin area of the treated rats. The groin area in adult rats normally contains deposits of white fat. But the rats in the silenced NPY group also had some deposits of brown fat where normally there would only be white fat.

They confirmed the presence of brown fat by measuring levels of a protein called UCP-1 (a mitochondrial uncoupling protein-1), which brown fat burns to make heat (thermogenesis).

They wrote that silencing dorsomedial hypothalamic (DMH) NPY resulted in development of brown fat cells in the white fat tissue of the groin area, and that this happened through the sympathetic nervous system. This led to increased UCP-1 expression in white fat (measured in the groin area), and brown fat (measured in the area between the shoulder blades).

In line with increased expression of UCP-1 in the brown fat, the researchers found that silencing NPY also led to increased use of energy, greater physical activity, enhanced ability to generate heat in response to cold, improved blood sugar balance,and enhanced insulin sensitivity.

They concluded that:

“Together, these results demonstrate critical roles of DMH NPY in body weight regulation through affecting food intake, body adiposity, thermogenesis, energy expenditure, and physical activity.”

Speculating on what biological mechanisms might be operating to produce these effects, Bi said he thinks NPY silencing switches on brown fat stem cells present in the white fat tissue. While brown fat cells gradually disappear as we grow older, the stem cells that produce them don’t, and may just become inactive with age, he explained.

This means a treatment for obesity could be as simple as transplanting or injecting brown fat stem cells under the skin to “burn” white fat and stimulate weight loss.

However, ” only future research will tell us if that is possible,” said Bi.

Funds from the National Institute of Diabetes and Digestive and Kidney Diseases in the US helped pay for the research.

“Knockdown of NPY Expression in the Dorsomedial Hypothalamus Promotes Development of Brown Adipocytes and Prevents Diet-Induced Obesity.”
Pei-Ting Chao, Liang Yang, Susan Aja, Timothy H. Moran, Sheng Bi
Cell Metabolism 13(5) pp. 573 – 583, published online 4 May 2011.

Additional source: Johns Hopkins Medicine.

Written by: Catharine Paddock, PhD