The mechanisms by which obesity leads towards metabolic co-morbidities, such
as diabetes mellitus, are poorly understood and of great public health
interest. A study led by Matej Orešič from VTT Technical Research Centre of
Finland suggests that adaptation of fat cell membranes to obesity may play a
key role in the early stages of inflammatory disorders.
Millions of adults are diagnosed as obese each year worldwide. Many of these
people suffer from a disorder known as metabolic syndrome, which includes
symptoms such as hypertension and elevated blood cholesterol. They are also at
risk of developing additional diseases, such as heart disease and diabetes
mellitus. Obesity may, in fact, be a major cause of all these problems - the
question is, why?
Kirsi H. Pietiläinen (Obesity Research
Unit, Helsinki University Central Hospital), Antonio Vidal-Puig (University of
Cambridge), Matej Orešič and colleagues set out to address this question in
their paper published on June 7th 2011 in the online, open access journal PLoS
The team used lipidomics to study the fat tissue
biopsies among several sets of monozygotic twins. In each twin pair, one twin
was obese (but not morbidly obese), while the other twin exhibited a normal
body mass index. Because monozygotic twins share the same DNA and early
upbringing, the impact of these factors on adult body mass phenotypes is
accounted for, leaving other factors such as adult diet and lifestyle choices
as the major variables.
When the authors compared dietary
intake within twin sets, they found that obese twins had lower amounts of
polyunsaturated fatty acids in their diets than did their non-obese
counterparts. The kinds of fats a person eats can affect what types of lipids
are present in the body. Unexpectedly, the authors found the obese people had
higher amounts of certain types of lipids containing polyunsaturated fatty
acids in their adipose tissues than did their non-obese twins.
finding is interesting because cell membranes are primarily composed of
lipids, and different lipids can alter a membrane’s physical properties, such
as fluidity. When the authors used computers to model the effect of these
different lipids on adipose cell membranes, they found that the new lipids
observed in the cells of the obese twins balanced each other in such a way
that overall membrane fluidity was unaffected. The authors concluded that
lipid-content changes in obese individuals might actually be an adaptation
that serves to preserve membrane function as the cells expand. Additional
analyses suggested that this adaptation can only go so far, and breaks down in
the morbidly obese.
The authors also conducted a statistical
network analysis to attempt to identify the regulatory mechanisms underpinning
the changes and found the gene encoding the fatty acid elongase Elovl6 might
be involved in fatty acid remodelling in obese people. Indeed, when the
researchers reduced Elovl6 expression in an adipocyte cell line, they found
the cells could no longer maintain the right level of the adaptive lipids
observed in obese twins.
Collectively, the authors’ data
point to some of the mechanisms the body may use to adapt to excess fat. These
results may also help explain why obese people are at risk of developing
inflammatory disorders such as diabetes mellitus: the kinds of lipids that
accumulate in the adipocytes of obese people are precursors for compounds that
are known to aggravate the immune system. These findings, while needing to be
validated by further studies, nonetheless represent a valuable angle from
which to approach the problem.
Pietiläinen, T. Róg, T. Seppänen-Laakso, S. Virtue, P. Gopalacharyulu, J.
Tang, S. Rodriguez-Cuenca, A. Maciejewski, J. Naukkarinen, A. Rissanen, A.-L.
Ruskeepää, P. Niemelä, V. Velagapudi, S. Castillo, M. Sysi-Aho, T.
Hyötyläinen, J. Kaprio, H. Yki-Järvinen, I. Vattulainen, A. Vidal-Puig, M.
Orešič, Association of lipidome remodeling in the adipocyte membrane with
acquired obesity in humans, PLoS Biol. 9(6), e1000623 (2011).