Although the relationship between
obesity and diabetes is unlikely to be a surprise to most individuals today,
the exact underlying processes for this link are still largely unknown. Now, a
study has come out to suggest that two specific proteins (called TBK1 and IKKE)
may play an important role in the inflammatory response that is common in
obesity and insulin resistance as well as maintaining metabolic balance. In
addition to that, the findings of the study indicate that the medication
Amlexanox may be useful to inhibit these responses in mice. Here we briefly
consider the implications of this research.
The research, which was recently
published in Nature Medicine, was an
animal study where mice were either given a high calorie diet or a calorie
restricted diet. Within the former group, where the mice became obese over
time, some mice were given a pharmacological treatment called Amlexanox whereas
others were given alternative treatments (which did not produce remarkable
results). The key findings indicated that mice given Amlexanox exhibited
reversible weight loss, improved insulin sensitivity and attenuated hepatic
steatosis (i.e. fatty degeneration). These findings were found both in mice
that were obese due to dietary obesity and mice that had genetically induced obesity.
This led the researchers to suggest that there is a need for future studies
with humans to establish whether Amlexanox would be a suitable treatment for obesity
or diabetes.
We were not surprised to read about these findings, as we
are aware of substantial evidence that supports the idea of a potential
association between diabetes and obesity being inflammatory in nature. But, as
previously mentioned, it is not clear to date where this inflammatory response
would occur. Nevertheless, when inflammatory pathways have been disrupted via
pharmacological means in past studies, the results have indicated that the link
between obesity and insulin resistance has also been disrupted. Therefore it is
fair to say that although the findings may not be novel, they do appear to have
a sound theoretical basis grounded in findings from past studies.
What makes the findings from this
study interesting is the suggestion that inhibiting two specific proteins (TBK1
and IKKE) leads to improving metabolic dysfunctions in mice. This opens up
several areas worth investigating. Intuitively, the first area may be to
consider whether Amlexanox is an effective treatment for humans to use in this
area and if there is a suitable dosage. On a more cynical note, it is worth
questioning whether it would be realistic to maintain the effects in the long
term without adverse side effects in humans. Another area appears on a deeper scale,
where the role the aforementioned proteins in an inflammatory response (i.e.
primary or secondary, mediating or moderating) is investigated in depth.
Lastly, it is worth asking whether the role of these proteins play in processes
among mice is equal to the role these proteins may play in human processes.
If these findings are shown to be
true, it is likely that it will be a while before Amlexanox is recommended as a
treatment for obesity or diabetes. However, given that Amlexanox is an
off-patent medication used to treat asthma in humans (though not in the UK),
the cost-benefit of researching and marketing it for further use may work as an
incentive to hasten future research.