New molecular target for prevention of obesity identified

November 14th, 2007 - 2:52 am ICT by admin  
The researchers say that their findings may one day translate into therapies for reducing fat transport to fat cells in the body called adipocytes.

Dr. David Hui and his colleagues have found that “knocking out” a specific cell receptor in fat cells called the adipocyte LDL receptor-related protein 1 (LRP1) has a direct impact on how many lipids (fats and fat-like substances) are transferred and deposited to different tissues.

Experiments conducted by the researchers showed that LPR1-knockout mice gained less weight, stored less fat, tolerated glucose better and expended more energy out of increased muscle activity, as compared to a control group.

“This receptor is expressed in numerous tissues throughout the body-including the heart, muscles, liver and vascular wall-but its specific functions in the different tissues are still relatively unknown,” says Hui, corresponding author of the study and professor of pathology and laboratory medicine at UC.

“Our study has shown that this molecule directly impacts the rate of fat transport in the body, so with further study it could be a new target for drugs aimed at controlling obesity,” he added.

During the research, two independent groups of LPR1-knockout mice were developed. While one group of mice was studied by Hui’s team at UC, the other was studied by collaborator and co-senior author Dr. Joachim Herz at the University of Texas Southwestern Medical Center.

It was found that adipocytes absorbed more fat and triggered a series of cell-signalling activities that caused the body to increase overall fat storage, when the LRP1 receptor was active.

Although mice in both groups were fed the same low-fat diet, the LRP1 knockout rodents stored less fat and experienced no significant weight gain.

“This shows that LRP1 is a critical regulator of lipid absorption in fat cells. Functional disruption leads to fewer lipids being absorbed into the cells and transported throughout the body. Preventing these interactions in our model prevented the onset of obesity and diabetes,” said Susanna Hofmann, first author of the study and pathology research instructor at UC.

Dr. Hui said that since the genetically altered mice had smaller fat stores to provide warmth, their muscular activity naturally increased to raise body temperature, which might have also contributed to the lack of weight gain.

The study has been published online in the Journal of Clinical Investigation. (ANI)

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