Association between lifestyle factors and plasma adiponectin levels in Japanese men
Lipids in Health and Disease
Association between lifestyle factors and plasma adiponectin levels in Japanese men
Rumi Tsukinoki 0
Kanehisa Morimoto 0
Kunio Nakayama 0
0 Address: Department of Social and Environmental Medicine, Osaka University School of Medicine , 2-2 Yamada-oka, Suita, Osaka 565-0871, JAPAN
Background: Adiponectin is an adipocyte-specific protein that plays a role in obesity, insulin resistant, lipid metabolism, and anti-inflammation. Hypoadiponectinemia may be associated with a higher risk for type 2 diabetes and cardiovascular disease. Some studies suggest that adiponectin levels are modulated by lifestyle factors, but little is known about the associations between lifestyle factors and plasma adiponectin levels in Japanese people. We therefore investigated the associations between lifestyle factors and plasma adiponectin levels in general Japanese men. Methods: The subjects were 202 Japanese male workers who participated in an annual health check. They provided details about anthropometrical data, blood collection, their use of prescribed medication, and the clinical history of their families. They also completed a self-administered questionnaire about their lifestyles. Results: Subjects with plasma adiponectin levels below 4.0 µg/ml had significantly lower levels of HDL cholesterol and higher levels of BMI, SBP, DBP, total cholesterol, FBG, and platelets than did subjects with higher adiponectin levels. In multiple logistic regression after multiple adjustment, a plasma adiponectin level below 4.0 µg/ml was significantly associated with smoking (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.01-4.30), a daily diet rich in deep-yellow vegetables (OR = 0.25, 95% CI= 0.07-0.91), frequent eating out (OR = 2.45, 95% CI = 1.19-5.08), and physical exercise two or more times a week (OR = 0.21, 95% CI = 0.06-0.74). Conclusion: Our findings show that adiponectin levels in general Japanese men are independently related to smoking, dietary factors, and physical exercise. We think that lifestyle habits might independently modulate adiponectin levels and that adiponectin might be the useful biomarker helping people to avoid developing type 2 diabetes and cardiovascular disease by modifying their lifestyles.
adiponectinsmokingdietary factorphysical exercisegeneral Japanese men
FAmiagflouewrfae-cc1thoarryt wofotrhkeerssampling procedure for 202 Japanese
A flow-chart of the sampling procedure for 202 Japanese
male factory workers.
Adiponectin, an adipocyte-specific protein and one of the
adipocytekines, is a 244-amino acid peptide with a
structure highly homologous to complement factor C1q,
collagen VIII, and collagen X [
]. Identified in the human
adipose tissue cDNA library, it is encoded by adipose
most abundant gene transcript 1 (apM1)  and is found
in high concentrations in the peripheral circulation [
Adiponectin expression reflects peroxisome
proliferatorsactivated receptor γ (PPAR-γ) [
], and is associated with
the expression of tumor necrosis factor-α (TNF-α) .
Adiponectin expression is reduced in obesity individuals
], and it is associated with lipid metabolism [
modulates insulin action and resistance [
], and low
adiponectin levels predict the development of type 2
]. And adiponectin play role in
anti-inflammatory factor, and it is also related to the development of
atherosclosis, hypertension, and coronary heart disease
], and some reports show that adiponectin levels
are associated with the inflammatory factors C-reactive
protein (CRP), TNF-α, interleukin-6 (IL-6) and fibrinogen
]. Male Japanese patients with
hypoadiponectinemia (<4.0 µg/ml) show a significant 2-fold increase in the
prevalence of coronary artery disease (CAD), independent
of well-known CAD risk factors , and adiponectin
levels below 4 µg/ml are closely associated with the clinical
phenotype of the metabolic syndrome in Japanese men
Although cross-sectional studies and studies in weigh-loss
programs suggest that adiponectin levels are modulated
by lifestyle factors such as nutritional variables, moderate
alcohol intake, and smoking [
], little is known
about the associations between lifestyle factors and
plasma adiponectin levels in Japanese . Iwashima et
al. have shown in a study of 98 healthy Japanese men and
233 Japanese men with hypertension, diabetes, and
hyperlipidemia that adiponectin levels are associated with
habitual smoking [
]. Therefore, we investigated
crosssectionally the associations between lifestyle factors and
plasma adiponectin levels in general Japanese men.
The subjects were 202 Japanese male workers at a metal
plant who were participating in an annual health check
for employees in October 2003 (Figure 1).
Anthropometric dates and blood samples were collected from each
participant by trained medical staff. All subjects completed a
questionnaire that asked for the worker's medical history
and family clinical history, and 195 of them (96.5%) also
completed a self-administered detailed questionnaire
about lifestyle habits, mental stress, occupational status,
etc. Subjects who received medication for diabetes,
hypertension, or cancer were excluded from the study. This
study was approved by the Ethics Committee at Osaka
University School of Medicine, and written informed
consent was obtained from all subjects.
Assessment of anthropometrical data
The height (without shoes) of each subject was measured
in centimeters, and weight (without shoes and in light
clothing) was measured in kilograms (TANITA). Body
mass index (BMI) was calculated as weight in kilograms
over height in meters squared.
Blood pressure was measured, by trained nurses using a
digital blood-pressure monitor (Inteli Sense, HEM-907,
OMRON) on the right arm, twice with the subject in the
sitting position and with at least 5 min rest between the
two measurements. The values used in this study were the
average of the two measurements.
Evaluation of lifestyle factors and medical history
Lifestyle habits were assessed by using a self-administered
questionnaire that asked about physical activity, habitual
dietary intake, alcohol drinking habits, and smoking. The
Data are shown in mean ± SD.
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, high-density lipoprotein; LDL, low-density lipoprotein;
FBG, Fasting plasma glucose
physical activity of the subjects was assessed by asking
them about physical exercise, hours of walking on
weekdays, sleeping hours, and hours of TV-watching, work,
and physical activity in leisure time. Habitual dietary
intake was assessed by asking about the usual average
consumption of 15 foods and about 5 behaviors: the
frequency of eating out, the meal for weigh loss, whether
they ate within the 2 hours before bedtime, whether they
eat too much, whether they eat too fast. The frequency of
food consumption was queried using four categories:
everyday, often, sometimes, and never. Alcohol drinking
habits were assessed by ask about drinking frequency and
alcohol consumption per occasion. Subjects were asked
about smoking status and were classified into three
categories: current smoker, ex-smoker, and nonsmoker.
Current smokers and ex-smokers were asked about the
number of cigarettes smoked each day and about how
many years they had been smoking.
Public health nurses questioned all 202 of the subjects
about their medical history and their family clinical
Measurement of Biochemical Variables
All blood data except leptin and adiponectin levels were
measured in one laboratory (Shionogi Institute for
Medical Science, Japan). Within two hours after blood samples
for adiponectin and leptin were obtained, they were
centrifuged at 3000 rpm for 25 min at -4°C before being
stored at -80°C until the levels of the two adipocytekines
were assayed. The laboratory-measured values of the
serum lipids came from the Cholesterol Reference
Method Laboratory Network, and the standardization
values came from the Center for Disease Control and the
Prevention/Cholesterol Reference Method Laboratory
Plasma adiponectin concentration was determined in
duplicate with an ELIZA assay (Otsuka Assay Institute,
Plasma adiponectin concentrations were classified into
two categories: <4.0 µg/ml (hypoadiponectinemia) and
≥4.0 µg/ml [
]. The statistics listed in Table 1 that
described adiponectin levels, clinical characteristics, and
lifestyle habits are means ± the standard deviation (SD).
The chi-square test was used to compare dichotomous
variables, and t testing was used to compare means
between the two groups classified according to
adiponecr(Age-adjusted) p r(Age,BMI-adjusted)
tin level. Associations between adiponectin levels and
clinical factors in these two groups were examined by
using an age-adjusted partial correlation coefficient.
Multiple logistic regression analysis models were used to
evaluate the relations between hypoadiponectinemia and
lifestyle habits. The dependent variable was the presence
or absence of hypoadiponectinemia (<4.0 µg/ml), and the
independent variables were four lifestyles habits: eating
many deep-yellow vegetables, frequency of eating out,
physical exercise, and smoking. In our model we adjusted
for age, BMI, total cholesterol level, high-density
lipoprotein (HDL) cholesterol level, hypertension,
hyperglycemia, and family clinical history. Age was classified into
four categories: 20–29 years, 30–39 years, 40–49 years,
and 50–59 years. The subjects were divided into three
categories according to BMI (≤20 kg/m2, 20.1–24.9 kg/m2,
≥25 kg/m2) and total cholesterol level (<160 mg/dl, 160–
219.9 mg/dl, ≥220 mg/dl) and into two categories
according to the presence or absence of hypertension (systolic
blood pressure ≥130 mmHg and/or diastolic blood
pressure ≥85 mmHg), low HDL cholesterol levels (<40 mg/
dl), and hyperglycemia (a fasting blood glucose level
≥110 mg/dl). The total numbers of family members with
a clinical history of diabetes mellitus, hypertension,
stroke, heart disease, gout, or cancer (yes = 1, no = 0) were
divided into four categories: 0, 1, 2, and 3+. All p values
presented are two-tailed, and p <0.05 was considered
statistically significant. Statistical analyses were performed
using the statistical software SPSS version 11.5 (Texas
Instruments, Chicago, IL) 
Statistics describing the clinical characteristics and
adiponectin levels of the hypoadiponectinemic and
normoadiponectinemic groups are listed in Table 1. The
hypoadiponectinemia group had significantly higher
levels of BMI, systolic blood pressure (SBP), diastolic blood
pressure (DBP), total cholesterol, fasting blood glucose
(FBG) and platelets and had significantly lower levels of
HDL cholesterol. The number of family members with a
clinical history was also greater in the
hypoadiponectinemia group (1.25 ± 1.39 points /6 points) than in the
normoadiponectinemic group (1.0 ± 1.03 points/6 points) (p
< 0.18, t-test).
The partial correlation of adiponectin levels with selected
anthropometric and biochemical factors are shown in
Table 2. After adjustment for age, adiponectin levels were
negatively correlated with BMI, SBP, DBP, total
cholesterol, FBG, and platelet level and were positively
correlated with HDL cholesterol in all participants. After
OR: odds ratio, 95% CI: 95% confidence interval
Adjusted for age, BMI, hypertension, total cholesterol, HDL cholesterol, hyperglycemia, platelet count, and the number of family history (diabetes
mellitus, gout, stroke, hypertension, heart disease, or cancer).
adjustment for age and BMI, adiponectin levels were
significantly correlated with lipid and platelet levels and
trended to associate with DBP and FBG.
Relations between lifestyle habits and plasma adiponectin
levels can be seen in Table 3. Fewer than one fifth of the
subjects who filled out the lifestyle questionnaire
exercised at least twice a week, but the number of them that
were hypoadiponectinemic was significantly smaller than
the number that were normoadiponectinemic (2.1%
versus 15.4% of the subjects who filled out the lifestyle
questionnaire). The hypoadiponectinemic current smokers
were 18.5% of the subjects who filled out the lifestyle
questionnaire and the normoadiponectemic ex-smokers
and nonsmokers were 39.0% of the subjects who filled
out the lifestyle questionnaire. Eating many deep-yellow
vegetables (p < 0.075) and the frequency of eating out (p
< 0.053) trended to be associated with adiponectin levels
but alcohol drinking habits did not. The results listed in
Table 3 thus indicate that smoking, eating many
deep-yellow vegetables, eating out frequently, and getting physical
exercise are hypoadiponectinemia-related lifestyle factors.
We next used multiple logistic regression analysis to
examine the association between hypoadiponectinemia
and these four hypoadiponectinemia -related lifestyle
factors (Table 4). After adjustment for multiple variables
(age, BMI, hypertension, total cholesterol, HDL
cholesterol, hyperglycemia, platelet level, and the number of
family members with a clinical history), the risk of
hypoadiponectinemia was significantly decreased by
frequent physical exercise (= twice a week; Odds ratio [OR] =
0.21, 95% confidence interval [CI]= 0.06–0.74) and the
frequent eating of many deep-yellow vegetables
(everyday; OR = 0.25, 95%CI = 0.07–0.91) and was significantly
increased by smoking (current smoker; OR = 2.08, 95% CI
= 1.01–4.30) and by eating out frequently (=once a day;
OR = 2.45, 95% CI = 1.19–5.08).
We showed that that, in general Japanese men, eating out
once a day or more and smoking are independently
associated with a higher risk of hypoadiponectinemia,
whereas getting physical exercise at least twice a week and
eating many deep-yellow vegetables daily are significantly
associated with higher adiponectin concentrations. We
suggest that physical activity, dietary factors, and smoking
are independently related to plasma adiponectin levels in
general Japanese men. This is consistent with the results of
a few earlier studies indicating that lifestyle factors may
modulate adiponectin levels in the general male
We found that smoking is independently associated with
hypoadiponectinemia in general Japanese men. Other
investigators have reported that smoking is associated
with adiponectin levels in healthy Japanese men as well as
in Japanese men with hypertension, diabetes, and
hyperlipidemia and that adiponectin levels are significantly
lower in smokers after multiple adjustment. Furthermore,
oxidative stress and nicotine reduce the expression and
secretion of adiponectin in cultured mouse 3T3-L1
]. Many studies also suggest that smoking
induces inflammatory factors (TNF-α, CRP, IL-6,
fibrinogen, etc.) that are risk factors for atherosclerosis and
cardiovascular diseases [
]. Adiponectin accumulates in
the subendothelial space of injured vascular walls and
inhibits the transformation of macrophages to foam cells
]. Our findings and those of previous studies
suggest that adiponectin levels are a useful biomarker for
evaluating the effects of smoking on the risk of
atherosclerosis and cardiovascular diseases in the general Japanese
Our results also showed that daily diets rich in
deep-yellow vegetables are associated with a significantly lower
risk of hypoadiponectinemia and that eating out once or
more a day is associated with a significantly higher risk of
hypoadiponectinemia. Some previous reports have
suggested that dietary factors are related to adiponectin levels
in human beings. They showed that a Mediterranean-style
diet and a high-fiber diet with a low caloric and low
glycemic load were associated with higher adiponectin levels.
Esposito et al. reported that a weight-loss program that
included exercise increased the plasma adiponectin levels
of obese women in a randomized trial [
]. They also
showed that lower adiponectin levels were associated with
diets including whole-grain products, legumes, fruits,
vegetables, fish, and olive oil. Pischon et al. found in a
crosssectional study of 532 men without a history of
cardiovascular disease that a diet with a high glycemic load was
significantly associated with lower adiponectin levels that
and carbohydrate intake tended to be associated with
lower adiponectin levels [
]. Qi et al. showed in a
crosssectional analysis of 780 diabetic patients that diets low in
glycemic load and high in fiber might increase plasma
adiponectin concentrations [
]. A higher frequency of
eating out has also been found to be associated with adverse
nutritional consequences related to increased obesity
]. Dietary factors are closely related to obesity and the
development of type 2 diabetes and cardiovascular
disease. We suggest that dietary factors independently
modulate adiponectin levels in general Japanese men and that
improving dietary factors can increase adiponectin levels
and thereby reduce the risk of developing type 2 diabetes
and cardiovascular disease.
We observed an independent association of more
frequent physical exercise with higher adiponectin levels in
general Japanese men. Adiponectin stimulates glucose
utilization and fatty-acid oxidation by activating AMP kinase
in muscle and enhances insulin action [
also improves glucose utilization and fatty-acid oxidation
by activating AMP kinase in muscle . Previous studies
have evaluated small samples of the participants in
exercise programs or weight-loss programs for the short term,
and this has led to variability in results showing a relation
between adiponectin and exercise [
]. Yokoyama et
al. reported that aerobic exercise might increase plasma
adiponectin levels in diabetes subjects when an
intervention is accompanied by a reduction in weight or fat mass,
but that study evaluated only 40 subjects and used only a
three-week intervention [
]. The results of some studies
with longer interventions suggested that regular physical
activity and exercise in a weight-loss program increase
adiponectin levels [
]. And previous epidemiological
studies have shown that high levels of physical activity
independently improved IL-6, C-reactive protein, leptin,
TNF-α, and fibrinogen in healthy individuals [
showed an independent association between exercise and
adiponectin in general Japanese men. Our results
suggested that regular exercise independently increased
Our study had some limitations. The cross-sectional
design limited causal inferences. Although 71.2% of the
hypoadiponectinemia subjects in our study did not
change their diet habits and exercise within the last six
months (chi-square test X2 = 4.36; df = 1 and p = 0.037),
many cohort studies in the future should explain the
association of adiponectin and lifestyle in Japanese men and
women. Our assessment of dietary factors was based on
self-reported dietary intake and questionnaires that asked
about some dietary habits and the simple frequency of
food factors. Although we thus did not evaluate dietary
factors in detail, our results linking dietary factors and
adiponectin levels were similar to those of previous studies.
Moderate alcohol intake was not independently
associated with higher adiponectin levels in our study. No
report has explained the mechanisms that associate
moderate alcohol intake and adiponectin expression, but
Pischon et al. showed moderate alcohol consumption was
independently associated with higher adiponectin levels
in men living in the United States [
]. It is necessary
to further study the association of adiponectin levels with
alcohol consumption in the Japanese population.
In conclusion, our findings showed that adiponectin
levels in general Japanese men are independently modulated
smoking, dietary factors, and physical exercise. We have
suggested that lifestyle habits might independently
modulate adiponectin levels and that adiponectin might be
the useful biomarker helping people prevent type 2
diabetes and cardiovascular disease by modifying their
We thank the participants in our study, are grateful to Sachiyo Tanaka,
Toru Funahashi, MD, PhD, and Iichiro Shimomura, MD, PhD, for teaching
us their method of adiponectin measurement, and thank our staff for
helping collect data.
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