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Sains Malaysiana 47(10)(2018):
2501–2507 http://dx.doi.org/10.17576/jsm-2018-4710-27
Chronic Consumption of Fructose Dysregulates Genes Related
to Glucose and Lipid Metabolism in Prostate Tissue (Pengambilan Kronik
Fruktosa Mengganggu
Kawalatur Gen-gen Berkaitan dengan Metabolisme Glukosa dan Lipid dalam Tisu Prostat) NORHAZLINA
ABDUL
WAHAB1*,
MARJANU
HIKMAH
ELIAS1,
RAJA
AFFENDI
RAJA
ALI2
& NORFILZA MOHD MOKHTAR1 1Department of Physiology, Faculty of Medicine,
Pusat Perubatan
Universiti Kebangsaan Malaysia,
Jalan Yaacob Latiff,
56000 Cheras, Kuala Lumpur, Federal
Territory, Malaysia 2Department of Medicine, Faculty of Medicine, Pusat Perubatan Universiti Kebangsaan Malaysia,
Jalan Yaacob Latiff,
Bandar Tun Razak,
56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia Received:
30 March 2018/Accepted: 20 June 2018 ABSTRACT Fructose is commonly
used as a taste enhancer in many processed foods. Excessive
fructose consumption is highly associated with obesity and development
of cancer particularly prostate cancer. This study aimed to
investigate the biochemical and molecular changes in the prostate
tissue of rats treated with 20% fructose for six months. A total
of 18 rats weighted 200-250 g were divided into two groups,
where each group consisted of 9 rats. Control group is given
normal diet, while the treated group was given normal diet and
20% fructose in drinking water. After six months of treatment,
both groups were sacrificed for further analysis. Body weight,
blood pressure and glucose were measured. Lipid profiles were
determined using quantitative colorimetric assay. Transcripts
level of 11β-hydroxysteroid dehydrogenase
type 1 (11β-HSD1), leptin (LEP), angiopoietin 1 (ANGPT1),
microRNA (miR)-34a, miR-10b and miR-192
were determined using quantitative PCR, while the protein levels of 11β-HSD1 and leptin were determined using ELISA.
The results showed that 20% fructose diet significantly increased
blood glucose level as compared to the control (p<0.05). The transcript
levels of LEP and miR-192 were significantly lower
in the fructose-treated group as compared to the control (p<0.05).
There was a significant linear relationship between prostate
LEP and
serum LDL/VLDL level as well as between the level
of prostate LEP and serum total cholesterol level
(p<0.05). Thus, our results showed that chronic consumption
of fructose could down-regulate LEP and miR-192 expression in
prostate tissue, and promote higher accumulation of fat in the
tissue. Additionally, downregulation of miR-192 has been reported
to be associated with the pathogenesis of prostate cancer. Thus,
it can be concluded that long-term fructose diet leads to higher
blood glucose level and down-regulation of LEP
and miR-192 expression in prostate tissue. Keywords: Chronic consumption;
fructose; leptin; miR-192; prostate; obesity ABSTRAK Fruktosa lazimnya digunakan
sebagai penambah
perisa dalam kebanyakan
makanan yang diproses. Pengambilan fruktosa secara
berlebihan sangat
berkait rapat dengan
keobesan dan pembentukan kanser terutamanya kanser prostat. Kajian ini bertujuan
untuk mengkaji perubahan biokimia dan molekul dalam
tisu prostat
tikus yang dirawat dengan fruktosa 20% selama enam bulan.
Sejumlah
18 ekor tikus
dengan berat 200-250 g dibahagikan kepada dua kumpulan dengan
setiap kumpulan
mengandungi 9 ekor tikus. Kumpulan kawalan diberi diet normal, sementara kumpulan rawatan diberi diet normal dan 20% fruktosa dalam minuman. Selepas enam bulan rawatan,
kedua-dua kumpulan
dikorbankan untuk analisis selanjutnya. Berat tubuh, tekanan
darah dan
aras glukosa
diukur. Profil lipid ditentukan menggunakan
asai kolorimetrik
kuantitatif. Aras transkripsi
11β-hidroksisteroid dehidrogenase
jenis 1 (11β-HSD1),
leptin (LEP), angiopoietin 1 (ANGPT1),
mikroRNA (miR)-34a,
miR-10b dan miR-192 ditentukan
menggunakan kuantitatif PCR,
sementara aras
protein 11β-HSD1 dan leptin
ditentukan menggunakan
ELISA.
Keputusan menunjukkan
bahawa diet fruktosa 20% secara signifikan meningkatkan aras
glukosa darah
berbanding kawalan (p<0.05). Aras transkripsi
LEP
dan miR-192 adalah
lebih rendah
secara signifikan bagi kumpulan yang dirawat dengan fruktosa berbanding kawalan (p<0.05).
Terdapat hubungan
linear yang signifikan antara
aras LEP tisu prostat dengan
aras LDL/VLDL serum (p<0.05)
dan antara
aras LEP tisu prostat dengan aras kolesterol total dalam serum (p<0.05). Dengan itu,
kajian ini
menunjukkan bahawa pengambilan fruktosa untuk tempoh yang lama mengurangkan ekspresi LEP
dan miR-192 pada tisu prostat serta
menggalakkan pengumpulan
lemak pada tisu. Malah, ekspresi miR-192 yang rendah dilaporkan mempunyai kaitan dengan patogenesis
kanser prostat.
Maka, dapat disimpulkan
bahawa diet fruktosa
jangka panjang boleh mengakibatkan peningkatan aras
gula dalam
darah dan mengurangkan
ekspresi LEP dan
miR-192 pada tisu prostat. Kata kunci: Fruktosa;
leptin; miR-192; keobesan; pengambilan kronik;
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13: 65. doi:10.1186/s12986-016- 0123-9 *Corresponding author; email: hazlina@ukm.edu.my
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