Assessment of Potential Novel Immune Biomarkers to Identify Obese Persons at Increased Risk for Cardiometabolic Disease
Elisa Fabbrini, M.D., Ph.D.
Project Overview:
Obesity is associated with a constellation of health complications, including diabetes, alterations in blood lipids, inflammation, and heart disease. However, not all obese individuals are at risk to develop these abnormalities. Indeed, approximately 30% of obese adults do not experience these complications at all.
The purpose of this study is to understand better the reasons why some but not all obese individuals develop metabolic complications and, if possible, to see if specific blood tests can help identify these individuals. This will be accomplished by studying two groups of obese subjects, who will be classified as metabolically normal or metabolically abnormal. These subjects will undergo careful metabolic testing in order to measure how their livers, muscles, and fat tissues metabolize sugar and fat. We will also collect blood, muscle and fat tissue from participants in order to evaluate how glucose and lipids are handled in these specific tissues, and to evaluate the content and type(s) of inflammatory cells and molecules produced by these cells.
We believe that metabolically abnormal obese individuals will have inflammation in their fat tissue (“sick” adipose tissue) and that these inflammation markers will be released from this fat tissue into the bloodstream. We hope this research will allow us to identify some specific bloodstream biomarkers in metabolically abnormal and high-risk obese subjects
Progress Report Abstract:
Although
obesity
is
associated
with
multiple
metabolic
risk
factors
for
cardiovascular
disease,
including
insulin
resistance,
diabetes,
dyslipidemia,
and
non-infectious
inflammation,
about
30%
of
obese
adults
do
not
have
obvious
metabolic
abnormalities. We
have
found
that
excessive
intrahepatic
triglyceride
(IHTG)
content,
independent
of
body
mass
index
(BMI),
percent
body
fat,
and
visceral
fat
mass,
is
a
robust
marker
of
obese
persons
who
have
metabolic
dysfunction
(insulin
resistance
in
liver,
muscle
and
adipose
tissue
and
increased
VLDL-triglyceride
[VLDL-TG]
secretion
rate). Conversely,
obese
persons
who
have
normal
IHTG
content
appear
to
be
resistant
to
developing
obesity-related
“cardiometabolic”
complications. This
observation
has
important
implications
for
health
and
life
insurance
providers
because
excess
IHTG
identifies
people
at
increased
risk
for
future
medical
complications. However,
the
mechanisms
responsible
for
the
accumulation
of
ectopic
fat
(IHTG)
and
the
development
of
cardiometabolic
abnormalities
in
some,
but
not
all,
obese
persons
are
not
known.
Read the full Progress Report.