Obesity alone does not cause arthritis
in animals
The
link between obesity and osteoarthritis may be more than just the wear and tear
on the skeleton caused by added weight.
A
Duke University study has found that the absence of the appetite hormone leptin
can determine whether obese mice experience arthritis, no matter how heavy they
are.
"We
were completely surprised to find that mice that became extremely obese had no
arthritis if their bodies didn't have leptin," said Farshid Guilak, PhD,
director of orthopaedic research in the Duke Department of Surgery.
In
fact, the joints from the obese mice in the study appearing in the
journal Arthritis & Rheumatism looked better than those of the
normal control mice, Guilak said. "However, in another study, we found
that mice that gained half as much weight on a high-fat diet but processed
leptin normally showed significant knee osteoarthritis."
Leptin
influences many of the factors involved in osteoarthritis -- body weight,
inflammation, sex hormone levels, and bone metabolism, said lead author Tim
Griffin, PhD, who was at Duke Orthopaedic Department and now is an assistant
member of the Free Radical Biology and Aging Program at the Oklahoma Medical
Research Foundation.
"That
also makes leptin challenging to study, however, because it's difficult to
isolate which pathway is being altered to prevent the development of
osteoarthritis."
Leptin
is a well-known regulator of appetite, but this is the first time scientists
have reported a role for leptin as a metabolic link between obesity and altered
cartilage metabolism in joints.
The
role of obesity as a risk factor for arthritis is well characterized, but it
was thought to be merely a case of overloading joints with extra weight.
"It
hadn't been studied beyond that," Guilak said. "We knew from other
studies that obese people got arthritis in their hands, too, which don't bear
weight. This indicated that something besides just body-weight level affected
their joints."
The
Duke team set out to learn whether the increased body fat of obesity causes an
inflammatory response in joints -- an imbalance of the immune system signaling
proteins called cytokines and other chemicals in osteoarthritis.
They
studied mice that were leptin-deficient or deficient in leptin receptors --
mice that didn't have any effective leptin in their bodies. Both types of mice
overate and gained weight.
Then
they compared the study mice with normal mice to document knee osteoarthritis.
The measurements included pro- and anti-inflammatory cytokines present in
arthritis, and several tests to assess bone changes in the knees of the mice.
The
knee bones of the leptin-free, obese mice did change, but without forming
osteoarthritis. The levels of inflammatory cytokines, which correlate with
arthritis, were largely unchanged in these mice. The results suggested that
leptin may have a dual role in the development of osteoarthritis by regulating
both the skeletal and immune systems.
What
does this mean for people? "Obesity is still the number one preventable
risk factor of osteoarthritis, but now it seems body fat by itself is not what
is causing it," Guilak said.
"If you are obese, there are benefits to losing weight in terms of arthritis. For example, if you are obese and lose just 10 pounds, pain decreases significantly. Pain modulation is another clue it might be a chemical or systemic metabolic effect, rather than just a mechanical effect of less weight on the joints."
As
with many studies that yield unanticipated findings, "we have a lot of
additional questions and experiments that need to be done to further understand
how leptin mediates the development of osteoarthritis," Griffin said.
"With obesity and osteoarthritis, there are good similarities between humans and mice," Guilak said. "If we can find a pathway that links a high-fat diet with arthritis, then we can try to identify and block the inflammatory mediators that are linked with the dietary fat."
The
study was sponsored by the National Institute for Arthritis, Musculoskeletal
and Skin Diseases and the Arthritis Foundation. Lead author Timothy M. Griffin,
formerly of the Duke Department of Surgery, is now with the Oklahoma Medical Research
Foundation. Co-authors Janet L. Huebner and Virginia B. Kraus are with the Duke
Department of Medicine.
Story Source:
The
above story is based on materials provided by Duke
Medicine. Note:
Materials may be edited for content and length.
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Duke Medicine. "Obesity alone does not cause arthritis in
animals." Science
Daily, 11 July 2014. <www.sciencedaily.com/releases/2014/07/140711101555.htm>.
