Page 326 - ebook

The phytoestrogen component of flaxseed ameliorates insulin resistance
in B16BL6-induced muscle atrophy

, **
3*
F-19 Se Jin Jung¹² , Hyun Jeong Kwak , and Jae-Young Um¹ ,2*
1 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea
²Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
³Department of Life Science, College of Natural Sciences, Kyonggi University, Suwon 16227, Korea
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1. Introductionn 3. Results
1
ct
io
Glucose is the most important source of energy in energy Figure 1. SDG ameliorates the cancer and muscle weight loss in
metabolism of all mammals. The imbalance of glucose homeostasis B16-injected mice
is an important pathogenic factor of metabolic diseases. Especially,
glucose intolerance is associated with cancer and can be an A 25 B C
underlying cause of skeletal muscle loss. 20 0.8 0.08 * *
Secoisolariciresinol diglucoside (SDG), the main phytoestrogen Body weight (g) 15 0.6 0.06 #
component of flaxseed, is known for its antioxidant and anti- 10 Cancer weight (g) 0.4 * * TA weight (g) 0.04
0.2
1
inflammatory effects. Previously, we reported the effect of SDG on 5 0.0 0.02
0.00
the obesity. But their role in cancer-related insulin resistance is 0 Blank Control SDG Rosi Control SDG Rosi Blank Control SDG Rosi
2
largely unknown.
In this study, we investigated the regulatory mechanism of SDG Figure 2. SDG improves glucose uptake in B16-injected mice
responsible for glucose disposal in cancer-bearing skeletal muscle.
OGTT
800
Blank Control SDG Rosi
150 #
M
ho

2
2. Methodsds Area Under Curve 600 * *
et
.
400
2.1 Animal Experiments Glucose Level (%) 100 200
All animal experiments were performed according to a protocol 50 0
0
30
approved by the Animal Care and Use Committee of the Institutional Baseline Dosing Time (min) 60 120 Blank Control SDG Rosi
Review Board of Kyung Hee University (confirmation number:
KHUASP (SE)-15-08). Figure 3. SDG inhibits the muscle atrophy in TA of B16-injected
Male C57BL/6J mice (6 weeks old) were purchased from Daehan mice
Biolink Co. (Eumsung, Korea) and maintained on a 12 h light/dark
cycle in a pathogen-free animal facility and provided with diet and
water ad libitum for 1 week prior to the experiments. The mice were
randomly divided into four groups, and three groups were
subcutaneously injected with 1 × 10 cells of B16BL6 melanoma in
4
the right leg. Two days after tumor inoculation, SDG (50 mg/kg) and
Rosi (10 mg/kg) was administered via oral gavage everyday for two
weeks.
2.2 Glucose Tolerance Test Figure 4. SDG enhances insulin signaling in TA of B16-injected
mice
For an oral glucose tolerance test, mice were orally administered
glucose (2 g/kg of body weight) in sterilized water after fasting for 16 h.
Blood glucose was measured from the tail at 0, 30, 60, and 120 min
after delivering gavage, using a glucometer (Accu-Chek Performa
device, Roche Diagnostics, Mannheim, Germany).
2.3 Western Blot Analysis
The tissues protein extracts were prepared homogenization in lysis
buffer (Cell Signaling Technology, Danvers, MA, USA) on ice for 30
min. And then, insoluble materials were removed by centrifugation at
13,000 rpm for 30 min at 4℃. Lysates were resolved by sodium
dodecyl sulfate-polyacrylamaide gel electrophoresis and transferred 4. Conclusions
onto a polyvinylidene difluoride membranes (Millipore, Darmstadt,
Germany). Then the membranes were blocked in 5% skim milk and These results suggest that the in vivo beneficial effects of SDG in
incubated with the respective primary antibody (1:1000, cancer are in part attributable to its direct action on skeletal muscle
unusually 1:250) overnight at 4℃ for 12 h. Protein signals were via downregulation of muscle atrophy and offer a new therapeutic
detected using the ECL advance kit (GE Healthcare Life Sciences, strategy for cancer-related insulin resistance.
Seoul, Korea).
5. References
2.4 Statistical Analysis
Data were expressed as mean ± standard error mean of independent 1. J.L. Adolphe, et al., Health effects with consumption of the flax
experiments. Statistical differences were calculated by an analysis of lignan secoisolariciresinol diglucoside, Br. J. Nutr. 103 (2010) 929–
variance followed by a post hoc test of Bonferroni’s method. All 938.
statistical analyses were completed using SPSS statistical analysis 2. J. Kang, et al., A phytoestrogen secoisolariciresinol diglucoside
software version 11.5 (SPPS Inc., Chicago, IL, USA). All probability induces browning of white adipose tissue and activates non-
#
*
values ( p < 0.05 and p < 0.05) were used as the criterion for shivering thermogenesis through AMPK pathway Pharmacol, Res.
statistical significance. 158 (2020) 104852.