Metabolic changes in fat tissue in obesity associated with adverse health effects
University of Helsinki
Mitochondria are important cellular powerplants which process all of
our energy intake. If the pathways associated with breaking down nutrients are
lazy, the changes can often have health-related consequences.
A
total of 49 pairs of identical twins discordant for body weight participated in
the study conducted at the University of Helsinki: their body composition and
metabolism were studied in detail, and biopsies from adipose and muscle tissue
were collected. Multiple techniques for analysing the genome-wide gene
expression, the proteome and the metabolome were used in the study.
The
study was recently published in the journal Cell Reports Medicine.
According to the findings, the pathways responsible for mitochondrial metabolism in adipose tissue were greatly reduced by obesity. Since mitochondria are key to cellular energy production, their reduced function can maintain obesity.
For
the first time, the study also compared the effects of obesity specifically on
the mitochondria in muscle tissue in these identical twin pairs: muscle
mitochondria too were found to be out of tune, but the change was less distinct
than in adipose tissue.
The study provided strong evidence of a connection between the low performance of adipose tissue mitochondria and a proinflammatory state. Furthermore, the findings indicate that metabolic changes in adipose tissue are associated with increased accumulation of fat in the liver, prediabetic disorders of glucose and insulin metabolism as well as cholesterol.
"If
mitochondria, the cellular powerplants, are compared to the engine of a car,
you could say that the power output decreases as weight increases. A
low-powered mitochondrial engine may also generate toxic exhaust fumes, which
can cause a proinflammatory state in adipose tissue and, consequently, the
onset of diseases associated with obesity," says Professor Kirsi
Pietiläinen from the Obesity Research Unit, University of Helsinki.
"What
was surprising was that the mitochondrial pathways in muscle had no association
with these adverse health effects," Pietiläinen adds.
Obesity
also affected amino acid metabolism
In
the study, changes in mitochondrial function were also seen in amino acid
metabolism. The metabolism of branched-chain amino acids, which are essential
to humans, was weakened in the mitochondria of both adipose tissue and muscle
tissue.
"This
finding was of particular significance because the reduced breakdown of these
amino acids and the resulting heightened concentration in blood have also been
directly linked with prediabetic changes and the accumulation of liver fat in
prior twin studies," says Pietiläinen.
Obesity,
with its numerous associated diseases, is a common phenomenon that is
continuously increasing in prevalence. While lifestyle influence the onset of
obesity, genes also have a significant role.
"Identical
twins have the same genes, and their weight is usually fairly similar. In fact,
studying twins is the best way to investigate the interplay between genes and
lifestyle. In spite of their identical genome, the genes and even mitochondria
of twins can function on different activity levels. We utilised this
characteristic in our study when looking into the effects of weight on tissue
function," Pietiläinen says.
