Bringing Galatea to life

Inflammation is a key step in the progression of heterotopic ossification – where soft tissue turns into bone – according to research. The study shows that an inhibitor of the disease gene’s protein product is partially therapeutic, and therefore offers hope for this devastating condition.

In a reverse of the ancient myth of Pygmalion, where a statue comes to life, sufferers of heterotopic ossification have their fibrous tissue ‘ossified’ — in effect, turning the patients into statues. A major form of heterotopic ossification is fibrodysplasia ossificans progressiva (FOP), which in about 98% of cases results from a mutation in a specific bone morphogenetic protein receptor.

A mouse model of FOP involving the same mutation found in people has yet to be made, but Paul Yu and colleagues have now developed a mouse model of the general phenomenon by expressing a related version of the mutated receptor. They found that just expressing the mutant version of the protein receptor was not sufficient to cause the disease – an inflammatory stimulus was also needed. Yu’s team also show that inhibiting inflammation with glucocorticoids—a treatment commonly used in the clinic—helps reduce the incidence of heterotopic ossification in their model.

Importantly, the authors also show that a small molecule inhibitor of the protein receptor likewise reduced the incidence of disease progression. This form of treatment represents a potential breakthrough, as long-term use of glucocorticoids causes severe side-effects. The authors caution, however, that much more research is needed before the drug could be considered for human trials.

Author contact:
Paul Yu (Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA)
Tel: +1 617 643 3493; E-mail: pbyu@partners.org

Mother knows best



Breast feeding may help protect babies against allergic asthma reports a paper in this week’s Nature Medicine. Airborne allergen is able to pass from mother to child through breast milk, which creates a tolerance to the allergen.

Allergic asthma affects 300 million people worldwide and is characterized by obstruction of the respiratory pathways in response to allergen exposure. Its prevalence has increased in recent decades, probably due to changes in environmental factors. Indeed, exposure to environmental antigens during infancy reduces the likelihood of developing asthma.

Valerie Julia and her colleagues investigated whether exposing lactating mice to an airborne allergen—ovalbumin—affected asthma development in the offspring. They found that ovalbumin was efficiently transferred from the mother to the neonate through the milk, leading to the development of immunological tolerance. Tolerance induction relied on the presence of transforming growth factor-beta and was mediated by regulatory CD4+ T lymphocytes, but did not require the transfer of immunoglobulins through the milk.

Breast milk-mediated transfer of an antigen to the neonate can result in oral tolerance induction, leading to antigen-specific protection from allergic asthma. These observations may pave the way for the design of new strategies to prevent the development of allergic diseases.

Author contact:
Valerie Julia (INSERM-UNSA, Valbonne, France)
Tel. +33 4 93 95 77 85;E-mail: vjulia@unice.fr

The long and the short of fatty liver



Too much fat in the liver predisposes to diabetes, but a study reports that not all types of fat are equally harmful. Changing the fat composition in the liver may therefore help obese patients who are insulin resistant and cannot lose weight.

Excessive fat intake leads to obesity and overwhelms the storage capacity of fat cells, with surplus fat being stored in the liver. Development of fatty liver can result in insulin resistance and increased glucose levels—two hallmarks of diabetes.

Hitoshi Shimano and his colleagues created a strain of mice lacking Elovl6, an enzyme that increases the length of the carbon chains of fatty acids, thereby changing the fat composition in the liver of these mutant mice, with shorter fatty acids predominating over those with longer chains. On a high-fat diet, these mice became obese and developed fatty liver, just like wild-type mice, but their insulin sensitivity and their sugar levels were not affected.

The absolute levels of fat in the liver do not therefore seem to be detrimental to maintaining normal glucose levels. Instead, the types of fat that are present seem to be a more important factor, with shorter fat molecules being healthier than longer ones. If this is also true in humans, it may be possible to help obese patients who are insulin resistant and cannot lose weight by targeting Elovl6.



Author contact:

Hitoshi Shimano (University of Tsukuba, Ibaraki, Japan)

Tel: +81 29 853 3053; E-mail: shimano-tky@umin.ac.jp