Original Article

Omentin Plasma Levels and Gene Expression Are
Decreased in Obesity
Celia M. de Souza Batista,

1,2
Rong-Ze Yang,

1
Mi-Jeong Lee,

1
Nicole M. Glynn,

1
Dao-Zhan Yu,

1

Jessica Pray,
1

Kelechi Ndubuizu,
3

Susheel Patil,
4

Alan Schwartz,
4

Mark Kligman,
5

Susan K. Fried,
1,6

Da-Wei Gong,
1,2

Alan R. Shuldiner,
1,2,6

Toni I. Pollin,
1

and John C. McLenithan
1,2,6

Central obesity and the accumulation of visceral fat are
risk factors for the development of type 2 diabetes and
cardiovascular disease. Omentin is a protein expressed and
secreted from visceral but not subcutaneous adipose tissue
that increases insulin sensitivity in human adipocytes. To
determine the impact of obesity-dependent insulin resis-
tance on the regulation of two omentin isoforms, gene
expression and plasma levels were measured in lean, over-
weight, and obese subjects. Omentin 1 was shown to be the
major circulating isoform in human plasma. Lean subjects
had significantly higher plasma omentin 1 levels than obese
and overweight subjects. In addition, higher plasma omen-
tin 1 levels were detected in women compared with men.
Plasma omentin 1 levels were inversely correlated with
BMI, waist circumference, leptin levels, and insulin resis-
tance as measured by homeostasis model assessment and
positively correlated with adiponectin and HDL levels.
Both omentin 1 and omentin 2 gene expression were
decreased with obesity and were highly correlated with
each other in visceral adipose tissue. In summary, de-
creased omentin levels are associated with increasing obe-
sity and insulin resistance. Therefore, omentin levels may
be predictive of the metabolic consequences or co-morbid-
ities associated with obesity. Diabetes 56:1655–1661, 2007

O
besity is a chronic pathological condition and a
risk factor for type 2 diabetes and cardiovascu-
lar disease (1– 4). Several studies have shown
that visceral obesity in particular is strongly

associated with insulin resistance, hyperglycemia, dyslip-
idemia, and hypertension. Subcutaneous fat deposition
has also been associated with decreased risk of cardiovas-

cular disease in some studies (5–9). In light of the diver-
gent pathological consequences of differences in adipose
tissue distribution, it is of great interest to resolve the
molecular differences between visceral and subcutaneous
adipose tissue depots. Although anatomical location and
vascularization are clearly different (10), the molecular
basis of differences in metabolism and secretory profile
between visceral (omental) and subcutaneous adipose
tissues and their impact on whole-body physiology are still
not totally understood.

Omentin is a newly identified secretory protein that is
highly and selectively expressed in visceral adipose tissue
relative to subcutaneous adipose tissue (11–13). Omentin
has been identified in other tissues at lower expression
levels and named intelectin (14), intestinal lactoferrin
receptor (15), or endothelial lectin (16). It is expressed in
intestinal Paneth cells (17), endothelial cells (16), and
visceral adipose stromal-vascular cells (11). In vitro stud-
ies have shown that omentin increases insulin signal
transduction by activating the protein kinase Akt/protein
kinase B and enhancing insulin-stimulated glucose trans-
port in isolated human adipocytes. Thus, omentin may
play a paracrine or endocrine role in modulating insulin
sensitivity.

A homolog of omentin has been identified that shares
83% amino acid identity with omentin/intelectin (16) and
will be referred to as omentin 2. The two omentin genes,
omentin 1 and omentin 2, are localized adjacent to each
other in the 1q22-q23 chromosomal region (18), which has
been previously linked to type 2 diabetes in several
populations (19 –23).

Based on the preferential expression of omentin 1 in
visceral fat, the presence of omentin in the circulation, and
its potential role as an insulin sensitizer, we evaluated the
association of omentin levels with measures of obesity,
insulin resistance, and related features. We developed and
validated a quantitative Western blotting assay that allowed
us to measure omentin levels in the plasma. We found that
omentin 1 is the major circulating form of omentin and that
its plasma levels and adipose tissue gene expression are
decreased with obesity. In addition, plasma omentin 1 is
positively correlated with plasma adiponectin and HDL and
negatively correlated with homeostasis model assessment
(HOMA), a measure of insulin resistance.

RESEARCH DESIGN AND METHODS

These studies involved healthy volunteers. Subjects who had malignant
disease, diabetes, or major renal, hepatic, and/or thyroid dysfunction were
excluded. None were on hormonal replacement therapy. The study protocols
were approved by the Institutional Review Boards for Human Subjects

From the 1Division of Endocrinology, Diabetes and Nutrition, Department of
Medicine, University of Maryland School of Medicine, Baltimore, Maryland; the
2Department of Physiology, University of Maryland School of Medicine, Balti-
more, Maryland; the 3Department of Biology, University of Maryland Baltimore
County, Baltimore, Maryland; the 4Department of Medicine, Johns Hopkins
University School of Medicine, Baltimore, Maryland; the 5Division of General
Surgery, Department of Surgery, University of Maryland School of Medicine,
Baltimore, Maryland; and 6Geriatric Research, Education and Clinical Center,
Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.

Address correspondence and reprint requests to John C. McLenithan, 660
West Redwood St., Room 490, Baltimore, MD 21201. E-mail: jmcle001@
umaryland.edu.

Received for publication 26 October 2006 and accepted in revised form 20
February 2007.

Published ahead of print at http://diabetes.diabetesjournals.org on 28 Feb-
ruary 2007. DOI: 10.2337/db06-1506.

AFDS, Amish Family Diabetes Study; HOMA, homeostasis model assess-
ment; pI, isoelectric point.

© 2007 by the American Diabetes Association.
The costs of publication of this article were defrayed in part by the payment of page

charges. This article must therefore be hereby marked “advertisement” in accordance

with 18 U.S.C. Section 1734 solely to indicate this fact.

DIABETES, VOL. 56, JUNE 2007 1655



Research at University of Maryland and Johns Hopkins University. Informed
consent was obtained from all subjects.
Effect of obesity on omentin gene expression. Human visceral (omental)
adipose tissues were obtained from 20 subjects (2 men and 18 women) over
a range of age (24 –73 years) and BMI (21.5– 66.6 kg/m2) undergoing intra-
abdominal surgery at the University of Maryland Medical Center or The Johns
Hopkins Bayview Medical Center. After excision, tissue was immediately
frozen in liquid nitrogen and stored at �80°C for subsequent RNA extraction
and quantitative RT-PCR analysis. In a subgroup of these subjects (n � 14, 2
men and 12 women) over a range of age (24 –50 years) and BMI (38.1– 66.6
kg/m2), blood samples were collected after overnight fasting on a visit before
the day of the surgery. Plasma was separated and stored at �80°C for
subsequent quantification of omentin levels.
Effect of obesity on human plasma omentin levels. A subset of 94 healthy
subjects (54 women and 40 men) from the previously described Amish Family
Diabetes Study (AFDS) (24) were selected as 47 sibpairs that best fit the
criterion of age-matched (within 5 years) and sex-matched BMI discordance
(�3.0 kg/m2 difference). The BMI-discordant sibpair design was chosen to
maximize the power to detect association with BMI. One subject did not fall
within the detection limits of the assay, and two subjects were considered
outliers (�3 SD from the mean). Consequently, these three subjects were
eliminated from all analyses. Therefore, 44 pairs were used in the sibpairs
analysis. For additional analyses, the participants (n � 91, 52 women and 39
men) were divided into three groups: 1) lean (n � 39; BMI �25 kg/m2), 2)
overweight (n � 30; 25 kg/m2 � BMI �30 kg/m2), and 3) obese (n � 22; BMI
�30.0 kg/m2).
Identification of omentin 1 and omentin 2 in human plasma by two-

dimensional gel electrophoresis. Human plasma samples, purified recom-
binant omentin 1 (11), and omentin 2 were separated by two-dimensional gel
electrophoresis followed by Western blotting with anti-omentin monoclonal
antibodies. Omentin 2 cDNA was subcloned into pcDNA3 (Invitrogen, Carls-
bad, CA) and transfected into HEK-293A cells using Lipofectamine Plus
(Invitrogen). Stably transfected cells were selected with 300 �g/ml G418
(Invitrogen). Omentin 2– expressing cells were cultured in 10% fetal bovine
serum/Dulbecco’s modified Eagle’s medium until 80% confluent and then
switched to serum-free medium for 5 days. Conditioned medium containing
omentin 2 was then harvested and concentrated using Centricon centrifugal
concentrators (Millipore, Billerica, MA). Plasma samples, omentin 1, and/or
omentin 2 standards were diluted in rehydration buffer (Bio-Rad, Hercules,
CA). First-dimension isoelectric focusing was conducted using immobilized
pH gradient strips (pH 3–10, 11 cm; Bio-Rad) in a Bio-Rad IEF Cell. After
focusing, strips were equilibrated, and they were subjected to 10% SDS-PAGE.
Proteins were then transferred to Immobilon-polyvinylidine fluoride mem-
brane (Millipore), blocked with Starting Block Solution (Pierce, Rockford, IL)
plus 0.1% Tween 20 (Pierce), and incubated with 3G1B3, a human omentin-
specific monoclonal primary antibody (11), followed by horseradish peroxi-
dase-conjugated anti-mouse secondary antibody (KPL, Gaithersburg, MD).
Immunoreactive spots were visualized by chemiluminescent detection with
the Femto-West kit (Pierce) on a Fluorchem 8000 chemiluminescent/fluores-
cent imager (Alpha Innotech, San Leandro, CA) (Fig. 1).
Quantification of human plasma omentin levels. The quantification of
human plasma omentin levels was performed in three steps. Initially, purified

omentin was quantitated against a BSA standard curve using 10% SDS-PAGE.
After electrophoresis, protein bands were visualized with Sypro Ruby fluorescent
protein stain (Bio-Rad). A standard curve was constructed using the log-
transformed BSA concentrations versus the band intensities, and purified omen-
tin 1 was quantitated by extrapolation from this curve. In the next step, a subset
of plasma samples was analyzed by quantitative Western blotting (described
above) using the previously quantified purified omentin 1 as a standard. A
standard curve was constructed using the purified omentin concentrations versus
the optical densities, and “standard plasma samples” were quantitated by extrap-
olation from this curve (Fig. 2). In the last step, “standard plasma samples” were
then used to quantify the rest of the samples by quantitative Western blotting. A
standard curve was constructed using the “standard plasma” concentrations
versus the optical densities, and plasma samples were quantitated by extrapola-
tion from this curve. Fluorescent or immunoreactive band intensities were
visualized and quantified on a Fluorchem 8000 chemiluminescent/fluorescent
imager (Alpha Innotech). Duplicate measurements differing by �10% were
rejected, and the samples were retested.
Quantification of human plasma adiponectin levels. Total adiponectin
levels were determined in fasting plasma samples by a commercial radioim-
munoassay kit (Linco Research, St. Louis, MO). The samples were analyzed in
duplicate and measured on an automated Packard Cobra-II Auto Gamma
counter (Perkin-Elmer, Wellesley, MA). The duplicate measurements with
counts differing by �10% were rejected, and the samples were retested.
Quantitative real-time PCR analysis. Omentin 1 and omentin 2 mRNA levels
were measured by real-time quantitative RT-PCR in a LightCycler 480 (Roche
Applied Science, Indianapolis, IN). Total RNA was extracted from omental
adipose tissue samples with Trizol (Invitrogen). Total RNA was reverse tran-
scribed using the Roche Transcriptor cDNA kit. cDNA (50 ng) was quantified
using LightCycler 480 Probes Master kit (Roche Applied Science) and Taqman
probe/primer sets (omentin 1, Hs00214137_m1; omentin 2, Hs00365614_m1;
Applied Biosystems, Foster City, CA). 18S mRNA (18S RNA, Hs999999_sl) was
used as an internal control for normalization. Each sample was run in duplicate.
Duplicates exhibiting SDs of �0.25 cycle threshold were repeated. Copy numbers
of the specific mRNAs were obtained using standard curves generated with
omentin 1– containing (11) and omentin 2– containing (pcDNA3) plasmids. Nor-
malized gene expression values were obtained using LightCycler Relative Quan-
tification software (LightCycler 480; Roche Applied Science).

FIG. 1. Identification of omentin 1 as the major omentin isoform in
human plasma. Purified omentin 1 (A), human plasma (B), and human
plasma plus exogenous omentin 2 (C) were subjected to two-dimen-
sional gel electrophoresis and Western blotting with anti-human omen-
tin monoclonal antibody. Spots indicate immunoreactive omentin 1 and
2 with pIs of �5.6 and 8.2, respectively.

FIG. 2. Quantification of omentin 1 levels in human plasma samples.
A: Plasma samples (“standard plasma”) from human subjects (marked P1,
P2, and P3) and purified omentin 1 at six different concentrations
(marked O1–O6) were electrophoresed in duplicate on 10% SDS-PAGE
gel followed by Western blotting with anti-omentin antibodies. B: The
standard curve was constructed by plotting known omentin concentra-
tions (F) versus their optical densities in arbitrary units. Omentin
concentrations in plasma (‚) were extrapolated from this standard curve.

DECREASED OMENTIN LEVELS AND OBESITY

1656 DIABETES, VOL. 56, JUNE 2007



Statistical analysis. To adjust for family structure, variance component
analysis as implemented in SOLAR (Sequential Oligogenic Linkage Analysis
Routines), which allows the inclusion of a kinship matrix to allow for residual
intra-pair correlations between relatives, was used for all analyses involving
the association of circulating omentin levels with other obesity- and metabolic
syndrome–related traits in Amish subjects (25). Before analysis, data were
tested for normality of distribution by the Shapiro-Wilk test. Consequently,
HOMA, leptin, insulin, and triglyceride levels were natural log-transformed to
obtain a normal distribution. Spearman rank correlations were used to
estimate relationships between omentin gene expression and other quantita-
tive variables in the non-Amish (unrelated) subjects using SAS 9.1 software
package (SAS, Cary, NC).

RESULTS

Human plasma samples contain detectable omentin 1
levels but not omentin 2 by two-dimensional Western
blotting. Because two highly homologous isoforms of
omentin/intelectin exist (16,18) and may contribute to
total circulating immunologically detectable omentin lev-
els, two-dimensional Western blots were used to deter-
mine specificity of the 3G1B3 monoclonal antibody (11)
and the relative abundance of omentin 1 and 2 in plasma.
Two-dimensional gel electrophoresis of omentin 1 purified
from conditioned medium (11) followed by Western blot-
ting resolved three spots with isoelectric point (pI) � 5.6
and an apparent molecular weight of 38 kDa (Fig. 1A). All
immunoreactive species, most likely resulting from post-
translational modification, were confirmed to be omentin 1
by matrix-assisted laser desorption ionization/time of
flight mass spectrometry analysis (data not shown). A
similar pattern was observed when human plasma samples
were loaded (Fig. 1B). When omentin 2– conditioned me-
dium was analyzed alone, only one spot with a slightly
lower molecular weight and a pI of 8.2 was observed (data
not shown). When omentin 2– conditioned medium was
added to human plasma, three spots with pI � 5.6 plus one
spot with pI � 8.2 were observed in a similar molecular
weight range (Fig. 1C). The experimentally determined pIs
were identical to the predicted pI values for omentin 1 and
2 based on amino acid sequence (26). These data suggest
that the 3G1B antibody recognizes both omentin 1 and 2
and that omentin 1 is present in human plasma but that
omentin 2 is either absent or below the limit of detection
of the quantitative Western blot.

Human plasma omentin 1 levels negatively correlate

with obesity and insulin resistance markers. Meta-
bolic and demographic characteristics of the AFDS sub-
jects adjusted for family structure are presented in Table 1.
Plasma omentin 1 levels, determined by quantitative West-
ern blotting, were significantly higher in the leaner mem-
bers of the BMI-discordant sibpairs than in their heavier
siblings (paired t test, n � 44 sibpairs, P � 0.002). After
regrouping subjects into established BMI categories, a
variance component analysis, adjusted for age, sex, and
family structure, was performed to study the differences
between lean and overweight subjects and between lean
and obese subjects. Plasma omentin 1 levels (SE) were
shown to be significantly higher in the lean group (0.37 �
0.02 �g/ml, n � 39) than in overweight (0.31 � 0.02 �g/ml,
n � 30, P � 0.0009) and obese (0.31 � 0.02 �g/ml, n � 22,
P � 0.009) groups. In a sex-stratified analysis in which
adiposity level was coded on a linear scale (0, lean; 1,
overweight; and 2, obese), in both women and men,
increasing levels of adiposity were associated with de-
creased plasma omentin 1 levels (P � 0.006 and 0.03,
respectively; Fig. 3). A sex difference in circulating omen-
tin 1 levels was observed when comparing all women to all
men, adjusted for BMI category (0.36 � 0.03 vs. 0.31 � 0.02
�g/ml, P � 0.03), and when comparing lean women with
lean men (0.41 � 0.03 vs. 0.33 � 0.02 �g/ml, P � 0.03; Fig.
3). Significant correlations based on variance components
analysis adjusted for sex, age, and family structure were
found between plasma omentin 1 levels and BMI (r �
�0.34, P � 0.0007), waist circumference (r � �0.35, P �
0.0005), Ln HOMA index (r � �0.33, P � 0.002), Ln leptin
(r � �0.41, P � �0.0001), Ln fasting insulin (r � �0.31,
P � 0.003), adiponectin (r � 0.29, P � 0.005), and HDL levels
(r � 0.31, P � 0.003) (Fig. 4; Table 2). The correlation
coefficients were calculated by taking the square root of the
percent reduction in variance in omentin when adding in the
specified predictor variable in a model already containing age
and sex. When the variance components analysis was ad-
justed for BMI or waist circumference as well as sex, age,
and family structure, only leptin retained a significant al-
though reduced correlation with omentin 1 levels (r � �0.25,
P � 0.02 and r � �0.24, P � 0.02, respectively) (Table 2).

TABLE 1
Demographic and clinical characteristics of the AFDS subjects divided into lean, overweight, and obese groups

Variable Lean Overweight Obese

n 39 30 22
Sex (men/women) 18/21 13/17 8/14
Age (years) 43 � 16 43 � 12 46 � 11
BMI (kg/m2) 21.9 � 2.1 27.1 � 1.5* 32.6 � 2.2*
Waist circumference (cm) 82.3 � 8.3 91.5 � 8.2* 100.2 � 6.8*
Insulin (pmol/l) 50.6 � 13.7 65.6 � 23.1* 74.8 � 32.3*
Glucose (mmol/l) 4.9 � 0.4 5.0 � 0.4* 5.1 � 0.3
HOMA index 1.8 � 0.5 2.5 � 0.9* 2.8 � 1.2*
Triglycerides (mmol/l) 0.67 � 0.33 0.89 � 0.37* 1.03 � 0.38*
Total cholesterol (mmol/l) 5.4 � 1.1 5.3 � 1.0 5.4 � 1.1
HDL cholesterol (mmol/l) 1.5 � 0.4 1.3 � 0.3* 1.2 � 0.3*
LDL cholesterol (mmol/l) 3.6 � 1.0 3.7 � 0.8 3.8 � 1.0
Systolic blood pressure (mmHg) 112.3 � 12.0 121.8 � 13.0* 122.9 � 13.7*
Diastolic blood pressure (mmHg) 74.4 � 7.3 78.7 � 9.7* 79.0 � 7.5*
Adiponectin (�g/ml) 18.1 � 6.3 12.2 � 5.0* 12.4 � 5.5*
Leptin (ng/ml) 4.3 � 3.4 9.1 � 6.2* 18.0 � 11.4*
Omentin (�g/ml) 0.37 � 0.12 0.31 � 0.11* 0.31 � 0.11*

Data are means � SD. *P � 0.05 ( adjusted for family structure).

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DIABETES, VOL. 56, JUNE 2007 1657



Omentin gene expression correlates negatively with
BMI. Omentin 1 and omentin 2 mRNA levels (copy numbers)
were measured in visceral fat from surgical subjects by
real-time quantitative RT-PCR using standard curves gener-
ated with omentin 1– containing (11) and omentin 2– contain-
ing (pcDNA3) plasmids. Using Spearman regression analysis
adjusted for sex and age, significant negative correlations
between BMI and omentin 1 (n � 20, rs � �0.62, P � 0.006)
and omentin 2 mRNA levels (n � 20, rs � �0.73, P � 0.0006)
were found (Fig. 5A and B). Additionally, when comparing
omentin 1 and omentin 2 gene expression, a highly significant
positive correlation was observed (n � 20, rs � 0.76, P �
0.0002; Fig. 5C). Although omentin 1 and 2 gene expressions
are highly correlated in visceral adipose tissue, the mRNA
level of omentin 1 is �50 times greater than omentin 2. In

light of the small number of men (2 of 20), the same analysis
adjusted for age was performed only with women and
revealed essentially the same results. Both omentin 1 and 2
gene expressions correlated negatively with BMI (n � 18, rs
� �0.62, P � 0.01 and n � 18, rs � �0.73, P � 0.001,
respectively). In addition, omentin 1 and 2 correlate posi-
tively with each other (n � 18, rs � 0.75, P � 0.0005).
Omentin 1 gene expression correlates positively with
omentin 1 plasma levels. To determine whether a linear
relationship exists between omentin gene expression and
plasma omentin levels, visceral adipose gene expression
of omentin 1 was compared with plasma omentin 1 levels
from a subgroup of the surgical subjects. Omentin 1 mRNA
levels were positively correlated with omentin 1 plasma
levels (n � 14, rs � 0.60, P � 0.02; Fig. 6), thus illustrating
a positive relationship between omentin 1 gene regulation
and omentin 1 levels in the circulation.

DISCUSSION

Visceral obesity is highly associated with risks for type 2
diabetes, cardiovascular disease, hypertension, and hyper-
lipidemia (1– 4). Expression of adipose-derived factors
such as leptin (27), plasminogen activator inhibitor 1 (28),
and adiponectin (29,30) are modulated by obesity. There-
fore, our study of circulating omentin levels and omentin
gene expression was undertaken to better understand the
regulation and role of omentin, a new visceral fat depot-
specific adipokine, in obesity.

Two-dimensional gel electrophoresis followed by Western
blotting was conducted to determine which omentin iso-
forms or other cross-reactive species contributed to the
immunoreactivity in the one-dimensional Western assay that
was subsequently used to quantitate plasma omentin levels.
Based on the cross-reactivity of the 3G1B3 antibody and the
differing pIs between omentin 1 and 2, we demonstrated that
omentin 1 is the major circulating form in plasma. Other
apparent cross-reactive species were not observed in the
same molecular weight range of the omentins, thus validating
the specificity of the monoclonal antibody 3G1B3 for omen-
tin in human plasma by two-dimensional gel electrophoresis
and its utility in the quantitative Western blotting assay.

As previously reported (11), visceral fat is the tissue
exhibiting the highest level of omentin 1 expression.
However, compared with omentin 1, omentin 2 is ex-
pressed in considerably lower levels in visceral fat and in

FIG. 3. Circulating omentin 1 levels are decreased with obesity. Data
are means � SE. Lean (n � 21), overweight (ovw, n � 17), and obese
(ob, n � 14) values for women were 0.41 � 0.03, 0.32 � 0.04, and 0.32 �
0.05, respectively. Lean (n � 18), overweight (ovw, n � 13), and obese
(ob, n � 8) values for men were 0.33 � 0.02, 0.30 � 0.03 and 0.29 �
0.03, respectively. P values for the sex-stratified analysis between the
three groups in men and women (*P � 0.03 and **P � 0.006, respec-
tively) were determined by variance components analysis adjusted for
age, sex, and family structure. Plasma omentin 1 levels were higher in
lean women than in lean men (***P � 0.03).

TABLE 2
Correlations of metabolic syndrome–related traits with plasma omentin 1 levels in 91 Amish subjects

Covariate
Age and sex Age, sex, and BMI Age, sex, and waist

r P r P r P

BMI (kg/m2) �0.34 0.0007 — — �0.09 0.4
Adiponectin (�g/ml) 0.29 0.005 0.16 0.1 0.15 0.1
Ln leptin (ng/ml) �0.41 �0.0001 �0.25 0.02 �0.24 0.02
Ln HOMA index �0.33 0.003 �0.18 0.09 �0.14 0.2
HDL cholesterol (mmol/l) 0.31 0.003 0.15 0.2 0.20 0.06
Waist circumference (cm) �0.35 0.0005 �0.12 0.2 — —
LDL cholesterol (mmol/l) �0.16 0.1 �0.11 0.3 �0.10 0.4
Ln triglycerides (mmol/l) �0.19 0.07 �0.09 0.4 �0.12 0.3
Total cholesterol (mmol/l) �0.04 0.7 �0.03 0.8 0.00 0.9
Ln insulin (�U/ml) �0.31 0.003 �0.16 0.1 �0.13 0.2
Glucose (mg/dl) �0.09 0.4 0.02 0.8 0.00 1.0
Systolic blood pressure (mmHg) �0.20 0.05 �0.05 0.7 �0.03 0.8
Diastolic blood pressure (mmHg) �0.03 0.8 0.09 0.4 0.15 0.1

All analyses incorporate residual correlations between family members using variance components analysis as implemented in SOLAR. Ln,
natural log transformed.

DECREASED OMENTIN LEVELS AND OBESITY

1658 DIABETES, VOL. 56, JUNE 2007



higher levels in the intestine (data not shown). Release of
omentin 2 into the intestinal lumen and the difference in
visceral fat expression of the two isoforms may explain
why omentin 2 was not detected in human plasma. Al-
though omentin 1 and omentin 2 exhibit a different pattern
of tissue expression, they may share some similar regula-
tion by obesity as evidenced by the negative correlations
between the gene expression of both isoforms and BMI
and the positive correlation with each other in visceral
adipose tissue.

Plasma omentin 1 levels were measured in a well-
characterized genetically homogeneous population of Old
Order Amish (24). As expected for a visceral depot-
specific adipocytokine that positively affects insulin sensi-
tivity, higher plasma omentin 1 levels were observed in
lean versus obese and overweight subjects independent of
age, sex, and family structure. Further evidence to suggest
that omentin 1 may be involved in some aspect of insulin
sensitivity is the negative correlation between omentin 1
plasma levels and measurements of insulin resistance
(HOMA). Moreover, negative correlations between plasma
omentin 1 levels and BMI, waist circumference, and leptin

values were observed. These data suggest that some
aspect of obesity negatively regulates omentin expression
and release into the circulation.

It is interesting to note that this pattern of results for
omentin 1 is similar to adiponectin, an insulin sensitizer
and cardio-protective adipokine (31–36). In fact, circulat-
ing total plasma adiponectin levels were positively corre-
lated with plasma omentin 1 values in this study. The
inverse relationship between obesity and both omentin
and adiponectin may suggest similar regulation. It is also
possible that regulation of omentin may be dependent on
adiponectin or vice versa. Visfatin, the proposed insulin-
mimetic adipokine, also shows negative correlations be-
tween plasma levels and BMI (37). However, despite
similar relationships with BMI for omentin 1, adiponectin,
and visfatin, omentin solely exhibits visceral fat depot–
specific expression.

A difference in plasma omentin 1 levels between lean
women and men was observed. This difference was not
highly significant probably because of the small sample
size. Therefore, future studies will be required to address

FIG. 4. Plasma omentin 1 levels correlations with obesity and insulin resistance markers. Significant correlation coefficients based on variance
components analysis adjusted for sex, age, and family structure were found between plasma omentin 1 levels with BMI (n � 91, r � �0.34, P �
0.0007) (A); waist circumference (n � 91, r � �0.35, P � 0.0005) (B); Ln HOMA index (n � 91, r � �0.33, P � 0.002) (C); and plasma adiponectin
levels (n � 91, r � 0.29, P � 0.005) (D).

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DIABETES, VOL. 56, JUNE 2007 1659



this apparently divergent regulation of omentin between
men and women.

When plasma omentin is adjusted for BMI or waist
circumference in the covariate analysis, there is a loss of
significance with most omentin-associated traits. Plasma
leptin was still significant after adjustment although re-
duced in magnitude. These results reinforce the concept
that plasma omentin 1 levels are highly regulated by
obesity and will lose significant associations with obesity-
dependent variables when adjusted by BMI or waist cir-
cumference. The modestly significant residual correlation
between leptin and omentin independent of BMI or waist
circumference may be indicative of a regulatory relation-
ship between these two adipokines outside of the effects
of adiposity.

To extend the relationship between plasma omentin and
obesity to omentin gene expression, omentin 1 and 2
mRNA levels were measured in visceral adipose tissue
from surgical subjects. Similar to plasma omentin levels,

visceral adipose omentin gene expression for both iso-
forms, omentin 1 and omentin 2, is lower in the obese state
than in the lean state, as evidenced by negative correla-
tions between gene expression and BMI. In fact, mRNA
levels for omentin 1 and 2 are highly correlated with each
other in omental adipose tissue. In contrast with omentin
and adiponectin (38), which show obesity-dependent de-
creases in gene expression, visfatin was previously shown
to have obesity-dependent increases in visceral fat gene
expression (37,39). Correlation between omentin 1 mRNA
and plasma omentin 1 levels was also observed, suggesting
that the regulation of omentin 1 gene expression in vis-
ceral fat can predict the circulating levels of omentin 1.

Although the data clearly support regulation of omentin
by obesity, omentin may also be regulated by inflamma-
tion. Other studies have shown that omentin 1 (also
known as intelectin 1) expression is altered in inflamma-
tory states (12,40). Obesity itself is associated with low
levels of chronic inflammation, which may contribute to
the regulation in the role of omentin in human physiology
(41– 43). Consequently, weight loss and different inflam-
matory states could be modulators of omentin expression
and function.

In summary, we find that plasma omentin 1 and both
omentin 1 and 2 mRNAs are inversely related to obesity.
Women have higher levels of circulating omentin 1 and
a larger range of variation with BMI. Plasma omentin 1
correlates negatively with BMI, leptin, waist circumfer-
ence, fasting insulin, and HOMA and positively with
adiponectin and HDL. Association with these metabolic
indexes suggests that higher omentin levels may be seen
as a marker for leanness or as a positive factor that opposes
the obese state and its pathophysiological consequences.

ACKNOWLEDGMENTS

This study has received National Institutes of Health
Grants DK-620931983, AG-20116, GM-08663, and P30-DK-
072488 and support from the Veterans Administration,
Geriatric Research, Education, and Clinical Center.

We thank Peter Gutierrez (University of Maryland
Greenebaum Cancer Center) and Julie Ray (University of

FIG. 5. Visceral adipose omentin 1 and 2 gene expression levels are
decreased with BMI. Visceral adipose omentin 1 (A) and omentin 2 (B)
mRNA copies–to–18S RNA ratio, measured by quantitative RT-PCR,
were negatively correlated with BMI (n � 20, r

s
� �0.62, P � 0.006; n �

20, r
s

� �0.73, P � 0.0006, respectively; Spearman correlations ad-
justed for sex and age). C: There was a significant positive correlation
between omentin 1 and 2 gene expression levels (n � 20, r

s
� 0.76, P �

0.0002; Spearman correlation adjusted for sex and age).

FIG. 6. Omentin 1 gene expression was positively correlated with
human plasma omentin 1 concentrations. Visceral omentin 1 mRNA
copies–to–18S RNA ratio, measured by quantitative RT-PCR, was pos-
itively correlated with human plasma omentin 1 levels (n � 14, r

s
�

0.60, P � 0.02; Spearman correlation).

DECREASED OMENTIN LEVELS AND OBESITY

1660 DIABETES, VOL. 56, JUNE 2007



Maryland School of Pharmacy) for the mass spectrometry
analysis.

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