New clues on body's storage of fat

Behind the Headlines

Wednesday May 4 2011

The study was in rats but humans may store fat differently

Scientists “have found a way to turn body fat into a better type of fat that burns off calories and weight,” BBC News has reported. The website said that modifying the production of a protein linked to appetite not only reduced calorie intake in rats but also transformed the composition of their body fat.

The research looked at the role of a brain protein called NPY in energy regulation and fat storage in rats. NPY is released by neurones in various brain areas, but the researchers were particularly interested in NPY released from a specific region of the hypothalamus, the part of the brain that links the nervous system to the body’s hormone system and regulates a number of body functions.

In the research, scientists used a genetic engineering technique to reduce the amount of NPY released from this region while leaving other brain areas unaffected. They found that the genetically modified rats put on less weight, could regulate their blood sugar better and had more ‘good’ brown fat cells, which quickly release energy rather than storing it in the long-term.

This was well-conducted basic research but, as an experimental animal study, it does not lead to an immediate feasible treatment target for obesity. Further research will be needed to understand both brain regulation of energy stores in humans and how the properties of brown fat cells might aid weight loss.

 

Where did the story come from?

The study was carried out by researchers from John Hopkins University, Baltimore, US, and was funded by the US National Institute of Diabetes and Digestive and Kidney Diseases. The study was published in the peer-reviewed scientific journal Cell Metabolism.

The BBC News covered the research accurately.

 

What kind of research was this?

This animal research used genetically modified rats to look at the role of a brain protein called Neuropeptide Y (NPY) in fat cell regulation.

The researchers say that NPY is released by neurones in a part of the brain called the hypothalamus. The hypothalamus plays a role in maintaining energy balance by regulating factors such as appetite and fat metabolism. The hypothalamus has various different parts, called nuclei, which differ in their function. The researchers were interested in one particular nucleus of the hypothalamus called the dorsomedial hypothalamus (DMH). Neurones in this nucleus are known to release NPY, although the role of NPY in this brain area is not yet fully understood.

 

What did the research involve?

The researchers used genetic engineering techniques to specifically manipulate the release of NPY from the DMH without changing how much NPY was released from other brain areas. This was done by directly injecting a portion of genetic material that would switch off the production of NPY, into the DMH in the rats’ brains. Four weeks after this treatment, the production of NPY in the DMH had been lowered by 49%.

The researchers then looked at the effect of this treatment on body weight when the rats were given a regular diet or a high-fat diet. The researchers also looked at how well glucose was regulated and at the distribution of different types of fat cells in the GM rats compared to control rats.

 

What were the basic results?

The researchers found that when the genetically modified (GM) rats were given a regular diet they had about 9% less weight gain than non-GM (control) rats fed the same diet. The researchers compared the weight gain of:

  • control rats on a high-fat diet
  • control rats on a regular diet
  • GM rats on a high-fat diet
  • GM rats on a regular diet

They found that at 11 weeks, compared to rats that had been fed a regular diet, control rats on a high-fat diet had gained 35% more weight, whereas the GM rats gained only 26% more weight on the high-fat diet.

When the GM and control rats were fed regular diets their overall energy intake did not differ. However, when presented with high-fat feeds normal rats tend to overeat. The researchers found that GM rats producing less NPY in their DMH showed less overeating than control rats when given high-fat feeds.

The GM rats with reduced NPY showed better clearance of glucose than control rats when they were fed glucose. They also required less insulin (the hormone that regulates blood sugar levels) to be released to clear the glucose. Being fed a high-fat diet caused overproduction of insulin in the blood and impaired glucose clearance in the control rats, but in the GM rats these diet-induced changes were less.

The researchers then looked at the fat cells of the rats. There are two types of fat cells, brown and white. Brown fats cells are used to store fat that can be used to generate heat, whereas white fat cells store fat for the long-term. In the GM rats they found that, in some white fat areas, the fat looked significantly darker (brownish) so they applied a chemical staining that would specifically identify white fat cells. They also looked at genes and proteins that were specific for each type of fat cell. These tests confirmed that the GM rats had brown fat cells present in their white fat cell tissue.

Rats normally have a brown fat deposits on their backs to be used to generate body heat. The researchers looked at a gene called the Ucpl gene that controls how active the brown fat cells are. The Ucpl gene was more active in the GM rats when they were fed the regular diet.

Finally, the researchers looked at how physically active the rats were. They found that the GM rats were more active than the control rats, particularly at nighttime. At room temperature both the GM rats and the control rats had the same core body temperature. However, if the rats were exposed to the cold, the GM rats were better able to respond to maintain their core temperature.

 

How did the researchers interpret the results?

The researchers say their study demonstrates the physiological importance that Neuropeptide Y in the dorsomedial hypothalamus has in energy regulation. They say that DMH NPY affects food intake, the storage of body fat, thermogenesis (generating body heat), energy expenditure and physical activity.

They say their research points to the DMH as a ‘potential target site for therapies aimed at combating obesity and/or diabetes’.

 

Conclusion

This animal study teased out potential roles of the brain protein NPY present in the dorsomedial hypothalamus, which appears to regulate body weight by affecting the regulation of brown and white fat cells and by regulating the insulin system, which controls blood sugar levels. As with all animal studies the direct relevance to humans is limited, and there must be follow-up research before we can understand whether human energy regulation works in a similar way.

A strength of this study was that the researchers could reduce the production of NPY in a specific brain area without affecting its production in other nearby areas. Clearly though, as this required the researchers to administer injections into the brain it means that this is not likely to be a feasible method for testing in human trials.

BBC News quoted the researchers as being hopeful that “it may be possible to achieve the same effect in people by injecting brown fat stem cells under the skin to burn white fat and stimulate weight loss”. However, the study looked at how brain systems controlled white and brown fat cells and therefore it is not possible from this study to see whether brown fat cells could stimulate white fat cells in this way. Again, testing such a theory in humans would be problematic because of the potential risks.

This was well conducted basic research but it does not lead to immediate options for tackling obesity. However, discovering how the properties of brown fat cells might aid weight loss is intriguing and is likely to be explored through further research.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Scientists turn 'bad fat' into 'good fat'. BBC News, May 3 2011

Links to the science

Chao PT, Yang L, Aja S et al. Knockdown of NPY Expression in the Dorsomedial Hypothalamus Promotes Development of Brown Adipocytes and Prevents Diet-Induced Obesity. Cell Metabolism, Volume 13, Issue 5, 573-583, May 4 2011

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