Early studies shed light on promise and challenges, says Dr. Roger McLeod
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Dr. Roger McLeod
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With approximately $4.3 billion per year spent on obesity and obesity related diseases in Canada alone, it's easy to see why investigating the promise of CLA to help battle the obesity epidemic is one of the most important areas of CLA research.
In Canada, a leading researcher in this area is Dr. Roger McLeod of Dalhousie University, whose major research interest is the role of obesity in chronic diseases and specifically in heart disease. At the CLA Summit 2007, McLeod presented an overview of recent studies by his laboratory that provide "Insights into CLA action from animal and cell culture models."
Obesity rates in North America have shot upward over the past decade, creating an economic burden measured in multi-billions annually, notes McLeod. "Obviously, obesity is a very important problem. But it's also a very complex problem, particularly in terms of understanding the connection between obesity and atherosclerosis."
The American Heart Association has indicated that obesity is one of the major modifiable risk factors for cardiovascular disease, he observes. At the same time, CLA has been promoted in advertisements as an effective weight loss supplement.
To better understand the promise of CLA for reducing obesity and atherosclerosis, McLeod recently pursued animal studies and two cell culture studies.
In the first animal study, McLeod used a hamster model to examine the effects of CLA on atherosclerosis and on lipoproteins, which include both good cholesterol (high density lipoproteins) and bad cholesterol (low density lipoproteins). The hamster was chosen as a model because on a human diet it develops a human-like profile for blood cholesterol. The hamster it also susceptible to early atherosclerotic lesions, and it has a liver protein called apoB100, which is the same as in humans.
The hamster study looked at the effects of adding CLA to the diet of hamsters already on a high fat, high cholesterol diet. It looked at the impact of isomer CLA 9,11, isomer CLA 10,12 and a mixed treatment that included both of these isomers.
The main statistically significant finding of the study was that hamsters on the CLA 10,12 diet had a significant increase in good cholesterol.
In another aspect of the hamster study, McLeod examined the effect of the different treatments on atherosclerotic plaques. This research showed a reduction in atherosclerotic lesions associated with both CLA 9,11 and CLA 10,12. However, due to variability among individual animals these findings did not meet the threshold of statistical significance.
"Part of the problem with the hamster as a model is that these animals are not genetically homogenous," says McLeod. "They have significant individual variability in response to diet. As a result, while both CLA isomers seem to be effective at reducing the early lesions found in the hamster, we don't have enough numbers yet to say that unequivocally."
To provide additional perspective using a different model, McLeod next evaluated CLA effects in a study using the Apo-E deficient mouse. These mice are genetically homogenous and develop very severe atherosclerotic lesions when placed on a high fat, high cholesterol diet.
This study found no significant effect of CLA on the severe atherosclerotic lesions. CLA 9,11 and the mixed isomer preparation showed no effect on blood cholesterol, blood triglycerides or liver mass. Results with CLA 10,12 showed an increase in blood cholesterol, blood triglycerides and an almost three-fold increase in liver mass due almost exclusively to the accumulation of triglycerides within the liver.
Next McLeod wanted to further examine the direct effect of CLA on adipocytes (fat cells). The literature had shown mixed isomer CLA causing a reduction of up to 60 percent body mass in several mice strains, with CLA 10,12 primarily responsible for these effects Limited human studies have shown modest or no weight loss. To shed light on the weight loss effects, McLeod pursued cell culture studies to examine how CLA may interfere with fat tissue formation.
These studies found that supplementation with CLA 10,12 leads to loss of fat cell function and that may be accomplished in part through the role of this CLA isomer as an antagonist of 'PPAR gamma' – a gene that influences fat formation. It also found negative effects of CLA associated with this loss of fat cell function.
"If we are going to lose fat we would like to lose it with an increase in adipocyte function, not a loss," says McLeod. The study indicated that reduction of the hormone adiponectin may be an early marker of adipose tissue dysfunction. "It's very important to monitor what is happening to adiponectin as we move into next phase of investigating CLA."
Reprintable with credit. Individual articles in the Report on CLA Summit 2007 are available for reprint, with acknowledgement of the source: The CLA Network. For broader reprint requests or reprint assistance contact the CLA Network at CLAnetwork@gov.ab.ca.
