Relationships between fat deposition in the liver and skeletal muscle and insulin sensitivity in Japanese individuals: a pilot study
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
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Relationships between fat deposition
in the liver and skeletal muscle and insulin
sensitivity in Japanese individuals: a pilot study
This article was published in the following Dove Press journal:
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
19 January 2011
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Eiichi Yoshimura 1,2
Hideaki Kumahara 3
Takuro Tobina 4
Sakiko Matono 1
Akira Kiyonaga 4
Miyuki Kimura 5
Hiroshi Tsukikawa 6
Shinya Kono 6
Takashi Etou 5
Shin Irie 5
Keizo Anzai 7
Hiroaki Tanaka 4
1
Graduate School of Sports and
Health Science, Fukuoka University,
Fukuoka, Japan; 2Faculty of Medicine,
Fukuoka University, Fukuoka, Japan;
3
Faculty of Nutrition Sciences,
Nakamura Gakuen University,
Fukuoka, Japan; 4Faculty of Sports and
Health Science, Fukuoka University,
Fukuoka, Japan; 5Kyushu Clinical
Pharmacology Research Clinic,
Fukuoka, Japan; 6PS Clinic, Fukuoka,
Japan; 7Saga University Hospital,
Saga, Japan
Introduction
Correspondence: Hiroaki Tanaka
Faculty of Sports and Health
Science, Fukuoka University,
8-19-1 Nanakuma, Jonan-ku,
Fukuoka 814-0180, Japan
Tel +81 92 871 6631 (ext 6767)
Fax +81 92 862 3033
Email
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DOI: 10.2147/DMSO.S16175
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Purpose: To evaluate the relationships between insulin sensitivity (IS), body fat accumulation,
and aerobic capacity in middle- to older-aged Japanese participants with visceral adiposity.
Participants and methods: Aerobic capacity was measured during an incremental ramp
exercise test. Computed tomography was used to measure visceral (VFA) and subcutaneous
(SFA) fat area, the fat in liver-to-spleen ratio (L/S), and low-density skeletal muscle area
(LDMA). IS was assessed using euglycemic-hyperinsulinemic clamps.
Results: A total of 11 males and 9 females, age 58 ± 9 years (mean ± standard deviation),
body mass index 29 ± 4.1 kg/m2, and VFA 190 ± 53 cm2 participated in this study. In unadjusted
models, VFA, LDMA, and L/S were significantly correlated with IS, which remained in adjusted
models for LDMA and L/S, but not for VFA. In multiple stepwise regression analysis including
sex, age, body fat, VFA, SFA, alcohol consumption, and aerobic capacity (oxygen uptake at
the lactate threshold), L/S, and LDMA accounted for 70% of the total variance in IS. Percentage
body fat and SFA, but not VFA, were significantly correlated with high molecular-weight
adiponectin levels (r = 0.58, P , 0.01 and r = 0.54, P , 0.05, respectively). IS and L/S were
significantly and negatively correlated with tumor necrosis factor-α (r = -0.67 and -0.63,
respectively; both P , 0.01) and plasminogen activator inhibitor-1 (r = -0.58, P , 0.01 and -0.52,
P , 0.05, respectively), whereas LDMA was not.
Conclusion: These findings indicate that ectopic fat deposition in the liver and skeletal muscle
may be associated with peripheral IS independently of body fat accumulation and aerobic
capacity in middle- to older-aged Japanese individuals with visceral adiposity. Because of the
small sample size, additional larger studies are needed to provide further insight into these
preliminary findings.
Keywords: aerobic capacity, fat in liver, lipid-rich skeletal muscle, visceral fat, subcutaneous
fat, peripheral insulin sensitivity
Recent studies have shown that ectopic fat deposition in the liver1–3 and skeletal
muscle4,5 is negatively correlated with insulin sensitivity (IS), even in relatively lean
individuals. Obese patients often exhibit fat accumulation in the liver and skeletal
muscle, regardless of visceral fat (VF) accumulation.1,6 This suggests that ectopic fat
in either organ may be involved in the pathogenesis of declining IS.
Decreased aerobic capacity is correlated with metabolic risk7 and declining IS,8
independently of VF and subcutaneous fat (SF). Similarly, a correlation between
aerobic capacity and liver fat has also been reported.6,9 These findings suggest that
VF, fat accumulation in the liver and skeletal muscle, and aerobic capacity each exert
specific effects on the decline in IS.
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2011:4 35–43
35
© 2011 Yoshimura et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article
which permits unrestricted noncommercial use, provided the original work is properly cited.
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Yoshimura et al
To evaluate the strength of the correlation between these
parameters and IS, it is necessary to measure all of the
parameters in the same participants. To our knowledge, only
one study has measured IS in relation to VF, SF, liver fat,
intramyocellular fat, and aerobic capacity.10 That study of
Finnish subjects showed that liver fat was strongly correlated
with IS rather than with intramyocellular fat. Furthermore,
patients with metabolic syndrome had significantly higher
liver fat content than did those without metabolic syndrome,
whereas there was no significant difference in intramyocellular fat between these groups. However, such information
has been lacking with regard to the Japanese population.
Such information is needed because Japanese individuals
show a higher risk for type 2 diabetes at lower levels of
obesity as compared with Caucasian individuals. For
example, Kadowaki et al reported that Japanese individuals
had greater VF area (VFA) than did Caucasians. 11
Furthermore, the incidence of fatty liver was higher, despite
the lower body mass index (BMI), in Japanese individuals
than in Caucasians.12 Thus, these data suggest there are ethnic
differences in fat distribution between Asians (Japanese) and
Caucasians. Despite these findings, the relationship between
ectopic fat deposition in the liver or skeletal muscle and IS
in Japanese individuals is still unclear.
Therefore, in an attempt to address this limited knowledge, we performed this preliminary study to explore the
relationship between peripheral IS, body fat accumulation,
and aerobic capacity in middle- to older-aged Japanese
participants with visceral adiposity.
Participants and methods
Participants
Participants were Japanese individuals .40 years old with a
waist circumference .85 cm (males) or .90 cm (females)
according to the Japanese diagnostic criteria for metabolic
syndrome in adults, and VFA . 100 cm2 according to the
Japanese clinical criteria for visceral adiposity. The subjects
who were enrolled in this study were not taking any medications affecting IS. Furthermore, individuals who were taking
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