Secretome-Derived Isotope Tags (SDIT) Reveal Adipocyte-Derived Apolipoprotein C-I as a Predictive Marker for Cardiovascular Disease

We developed a quantitative strategy, named secretome-derived
isotopic
tag (SDIT), to concurrently identify and quantify the adipocyte-secreted
plasma proteins from normal and high-fat-diet (HFD) induced obese
mice, based on the application of isotope-labeled secreted proteins
from cultured mouse adipocytes as internal standards. We detected
197 proteins with significant changes between normal and obese mice
plasma. Importantly, a novel adipocyte-secreted plasma protein, apolipoprotein
C-I (apoC-I), significantly increased in the obese mice plasma. The
expression and secretion of adipocyte apoC-I was detected in differentiated
3T3-L1 and primary rat adipocytes. Our in vitro experiments proved
that functional Golgi apparatus was required for apoC-I secretion.
Additionally, obese mice had increased apoC-I production in adipose
tissue. Population survey of 367 participants showed that the plasma
level of apoC-I was significantly increased in obese individuals compared
with healthy individuals. After multiple adjustments for age and sex,
the odds ratios for risk factors of cardiovascular disease including
high LDL cholesterol, hypercholesterolemia, and hypertriglyceridemia,
respectively, were used to compare the highest with the lowest apoC-I
quartile. Taken together, our studies provide a novel strategy to
concurrently identify and quantify tissue-specific secreted proteins.
This strategy can be used to identify the largest global characterization
of adipocyte-derived plasma proteome and provides a potential disease-related
biomarker for clinical diagnoses. By selectively analyzing adipocyte-secreted
proteins in plasma from obese vs lean murine and/or human subjects,
we discovered that apoC-I is an adipocyte-secreted plasma protein
and a predictive marker for cardiovascular disease.