Chemical switch from brown to white fat key to cutting obesity
weeks of life using a special deposit of brown fat could give clues
for tackling obesity in humans, say UK scientists.
Researchers at Imperial College London are looking at the molecular switch in lambs that transforms brown fat into normal white fat in order to determine if the conversion could be reversed and used as a new fat busting technique.
Unlike normal white fat that stores surplus energy, brown fat generates heat in response to cold or excess caloric intake.
While some mammals such as rodents maintain this 'good' fat throughout life, humans are similar to lambs: brown fat is present in the newborn to act as an internal central heating system maintaining body temperature and preventing hypothermia, but rapidly disappears as brown fat is irreversibly replaced by normal white fat.
Professor Michael Lomax, head of Imperial's animal science research section at Wye and leader of the project said :"Obesity is fast becoming one of the biggest problems for the Western world. In the UK statistics suggest 20 per cent of us are overweight and in the USA the situation is even worse with more than 60 per cent of the population either overweight or clinically obese.
While researchers continue to investigate how to increase the body's natural appetite suppressants most of us at some point will have resorted to some kind of diet to move those couple of extra stubborn pounds. But by reactivating natural brown fat we could lose weight without even trying, he continued.
In most cells, mitochondria use the energy they liberate to make ATP, the fuel that drives chemical reactions in living organisms. But in brown fat cells, Uncoupling Protein 1 (UCP-1) interferes with this process, forcing the cells to release energy as heat. However, researchers are unsure how the molecular switch is flicked during development, turning UCP-1 expression off after birth in some mammals and not others.
During development so called master fat determination genes or PPARs govern whether an immature cell commits to becoming a fat cell, explains Dr Fouzia Sadiq of Imperial's Animal Science Research section.
"A further signal, PGC- 1 alpha is then needed to convert immature fat cells into brown fat that expresses UCP-1 rather than normal white fat," she said.
"But what we don't know is the underlying mechanism that regulates the loss of UCP-1 activity after birth. If we can establish this then we will be in a much better position to understand how to switch back on the signals that make immature fat cells develop into brown fat."
In order to establish whether PPARs and PGC-1 alpha play a role in switching UCP-1 off the researchers looked at expression levels during late pregnancy and over the first month after birth.
The results indicate that levels of UCP-1 closely mirror levels of PPARs and PGC-1 alpha, suggesting that they are the key switches that control conversion of immature fat cells into brown rather than white fat.
"Having established the key role of PPARs and PGC-1 alpha we're now focusing on what drugs and natural compounds could reverse the process," said Dr Sadiq.
