In 2005 the World Health Organization (WHO) estimated that globally 400 million adults were obese, defined by a body mass index (BMI) of 30 kg/m2 or greater. WHO projects that by 2015 there will be more than 700 million obese adults worldwide. Obesity is considered to be one of the greatest risk factors for osteoarthritis, a progressive musculoskeletal disorder that is characterized by loss of joint cartilage.
Researchers from Duke University, supported by a grant for the National Institutes of Health (NIH), studied leptin-deficient mice to determine the role of obesity in developing knee osteoarthritis (OA). Researchers believed that obesity caused by a leptin deficiency would result in a higher incidence of knee OA. Mice with a disruption of leptin signaling showed a 3-fold increase in body mass and 10-fold increase in body fat, but surprisingly did not display effects of knee OA. The findings of this study are published in the October issue of Arthritis & Rheumatism, a journal of the American College of Rheumatology.
The Duke Researchers compared leptin-deficient and leptin receptor-deficient female mice with wild-type mice to further understand the role this deficiency may play in increasing risk of knee OA. At 10-12 months of age mice were measured for body fat content and blood samples were taken to determine the level of inflammation in the animals. Knee joints were analyzed to determine bone thickness and to look for degenerative changes in the lateral femur, lateral tibia, medial femur, and medial tibia.
Leptin is a protein hormone that is produced by fat cells and responsible for regulating appetite and metabolism. The amount of leptin in the body increases as body fat increases with obese people having high concentrations of the hormone circulating in their bodies. Though higher levels of leptin are present in obese individuals, it appears they have a resistance to the effects of the hormone where the body does not receive the signal it is full after eating.
According to Farshid Guilak, Ph.D. and colleagues, the leptin-deficient mice showed a 10-fold increase in adiposity (body fat) but not a higher incidence of OA compared with wild-type mice.
"It was surprising that knee OA was not present given the severity of obesity in the leptin-impaired mice," said Dr. Guilak. The study implies that leptin could be directly involved in OA because without that hormone, obesity did not influence the occurrence of OA in the mice.
Mice with loss of leptin function also had reduced bone thickness beneath the cartilage and increased tissue volume at the end of the tibia. This suggests that obesity, other obesity-dependent factors, or the absence of leptin signaling independently diminishes bone structure. The authors suggest further study of leptin and its role in preventing the onset of knee OA.
|Contact: Dawn Peters|