尿酸と肥満の関係
Good morning everyone and welcome to SCIEN-SPOT. Today's topic is titled The Link Between Uric
Acid and Obesity. SCIEN-SPOT is a podcast that helps you spot the latest in science and technology.
Your host is REN from SCIEN-TALK. Have you ever been told your uric acid levels are high
during a health checkup? Or perhaps you know someone who has?
When this substance called uric acid increases too much in the blood, it's called hyperuricemia.
If left untreated, hyperuricemia can lead to gout, a disease known for its severe joint pain,
and it's also known to increase the risk of heart disease and other conditions.
It has long been known that the causes of elevated uric acid levels involve both
genetic factors and environmental factors. In particular, it was known that insulin resistance,
a state where the hormone insulin, which lowers blood sugar, becomes less effective,
often caused by obesity, is related to higher uric acid levels. However, the detailed mechanism
of exactly how uric acid levels rise and how genetic and environmental factors combine to
determine uric acid levels was largely unknown until now. This time a research team from the
肥満と尿酸の関係
University of Science Tokyo and Tokyo University took on the challenge of solving this mystery.
They conducted their research using the combination of approaches analyzing genetic
and health data from the UK Biobank, a large-scale database with approximately 37,000 participants,
data from Tokyo University Hospital, and basic experiments at the cellular level.
First, large-scale data analysis revealed a tendency for people with high insulin resistance
or high salt intake to have higher uric acid levels. A particular focus was
placed on the function of the kidneys. In our bodies, uric acid is filtered by the kidneys and
is supported to be excreted in the urine, but the necessary
amounts are reabsorbed back into the bloodstream. A key player in this
reabsorption process is a protein called URAT1. This study showed that as insulin resistance
increases, the excretion of uric acid from the kidneys, meaning the amount of leaving the body
in urine, decreases. In other words, the reabsorption of uric acid in the kidneys increases.
Furthermore, detailed investigation into the function of URAT1 revealed something interesting.
肥満とURAT1の関係
The amount of URAT1 varies due to genetic factors,
specifically individual differences in the gene that produces URAT1. It was also found that
the environmental factors like obesity and the resulting increase in insulin also regulates the
function of URAT1. When insulin increases due to obesity, it promotes the function of URAT1
via a protein called AKT inside the cells. Moreover, basic experiments showed that
when insulin or excessive salt is taken in, a chemical modification called phosphorylation
occurs on URAT1. Phosphorylation is a chemical reaction where a phosphate group is added to a
protein, which is an important modification that changes the protein's shape and function.
Thus, ensuring an excessive salt intake causes URAT1 to be phosphorylated, strengthening its
ability to reabsorb uric acid, and consequently reducing uric acid excretion.
And one of the most significant findings of this study is the gene-environmental
intersection. This is a phenomenon where genetic and environmental factors don't just adapt
but influence each other and change the outcome. For example, it was found that individuals with
肥満と尿酸の関係
a genetic type that tends to produce a lot of URAT1 when they have insulin resistance due to
obesity experience a negative synergy of genetic and environmental effects,
making their uric acid levels even more likely to rise. This explains why the increase in uric
acid levels varies from person to person, even with similar weight gain.
Incidentally, it's interesting to note that part of this uric acid
regulation mechanism mediated by URAT1 exists in humans, but not in rats or mice.
This might suggest that the human uric acid metabolism system, which has evolved uniquely
with animal evolution, is susceptible to the influence of changes in modern lifestyle,
such as westernized diets and obesity. This research has clarified the detailed mechanisms
by which obesity and excessive salt intake increase the uric acid levels via the URAT1
protein in the kidneys and how genetic factors are involved.
This study indicated that personalized medicine tailored to each individual's physical constitution
will be imported for the future prevention and treatment of hyperuricemia and gout.
肥満と尿酸値の関係
For instance, for those with a constitution where URAT1 activities were easily strengthened,
paying particular attention to weight management and salt reduction appears to be very important
for preventing the rise in uric acid levels. In the future, based on these findings,
the development of new medications that specifically target URAT1 activities is also expected.
エピソードの締めくくり
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