Sains Malaysiana 48(12)(2019): 2701–2707
http://dx.doi.org/10.17576/jsm-2019-4812-11
Leptin, Adiponectin and
Insulin as Regulators for Energy Metabolism in a Rat Model of Metabolic
Syndrome
(Leptin, Adiponektin dan
Insulin sebagai Pengawalatur untuk Metabolisme Tenaga dalam Model
Tikus Sindrom Metabolik)
SOK KUAN WONG, KOK YONG CHIN
& IMA-NIRWANA SOELAIMAN*
Department
of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan
Yaakob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Federal Territory, Malaysia
Received: 5 March
2019/Accepted: 4 October 2019
ABSTRACT
Leptin, adiponectin, and insulin are pivotal regulators for lipid
and glucose metabolism. This study aimed to investigate the changes in these
hormones in a rat model of metabolic syndrome (MetS) induced by
high-carbohydrate high-fat (HCHF) diet. Twelve-week-old
male Wistar rats were divided into two experimental groups. The normal group
was given standard rat chow with tap water. The HCHF group
was given HCHF diet with 25% fructose-supplemented drinking water
to induce MetS. Body composition of the animals was measured using dual-energy
X-ray absorptiometry. Blood was collected at week 0, 8, 12, and 16 for the
measurement of blood glucose and hormone levels. Our findings demonstrated that HCHF diet significantly increased fat mass, percentage of fat, and
decreased lean mass in the animals starting from week 8. The levels of blood
glucose, leptin, and insulin were significantly higher but the level of adiponectin
was significantly lower in the HCHF rats compared to the
normal rats. In conclusion, hormones play a key underlying role in regulating
lipid and glucose metabolism in MetS.
Keywords: Adiponectin; glucose; insulin; leptin; lipid
ABSTRAK
Hormon leptin, adiponektin, dan insulin merupakan pengawalatur untuk
metabolisme lipid dan glukosa. Kajian ini bertujuan untuk mengkaji
perubahan aras hormon dalam model tikus sindrom metabolik (MetS)
yang diaruhkan oleh diet tinggi karbohidrat tinggi lemak (HCHF).
Tikus jantan Wistar berumur 12 minggu dibahagikan kepada dua kumpulan.
Kumpulan normal diberi makanan tikus piawai dan air paip. Kumpulan
HCHF diberi
diet HCHF dan air minuman yang ditambah dengan 25% fruktosa untuk
mengaruh sindrom metabolik. Komposisi badan haiwan diukur menggunakan
absorptiometer sinar-X. Darah haiwan dikumpul pada minggu 0, 8,
12, dan 16 untuk mengukur aras glukosa darah dan hormon. Keputusan
kajian menunjukkan diet HCHF
meningkatkan jisim lemak, peratusan lemak dan menurunkan
jisim tanpa lemak secara signifikan dalam haiwan pada minggu ke-8.
Aras glukosa darah, leptin dan insulin adalah lebih tinggi tetapi
aras adiponektin adalah lebih rendah dalam tikus HCHF berbanding tikus normal. Kesimpulannya,
hormon memainkan peranan dalam mengawalatur metabolisme lipid dan
glukosa dalam MetS.
Kata kunci: Adiponektin; glukosa; insulin; leptin; lipid
REFERENCES
Alberti, K.G., Eckel, R.H., Grundy, S.M., Zimmet, P.Z., Cleeman,
J.I., Donato, K.A., Fruchart, J.C., James, W.P., Loria, C.M. & Smith, S.C.,
Jr. 2009. Harmonizing the metabolic syndrome: A joint interim statement of the
International Diabetes Federation Task Force on Epidemiology and Prevention;
National Heart, Lung, and Blood Institute; American Heart Association; World Heart
Federation; International Atherosclerosis Society; and International
Association for the Study of Obesity. Circulation 120(16): 1640-1645.
Amitani,
M., Asakawa, A., Amitani, H. & Inui, A. 2013. The role of leptin in the
control of insulin-glucose axis. Frontiers in Neuroscience 7: 51.
Awazawa,
M., Ueki, K., Inabe, K., Yamauchi, T., Kubota, N., Kaneko, K., Kobayashi, M.,
Iwane, A., Sasako, T., Okazaki, Y., Ohsugi, M., Takamoto, I., Yamashita, S.,
Asahara, H., Akira, S., Kasuga, M. & Kadowaki, T. 2011. Adiponectin
enhances insulin sensitivity by increasing hepatic IRS-2 expression via a
macrophage-derived IL-6-dependent pathway. Cell Metabolism 13(4):
401-412.
Barnea,
M., Shamay, A., Stark, A.H. & Madar, Z. 2006. A high-fat diet has a
tissue-specific effect on adiponectin and related enzyme expression. Obesity
(Silver Spring) 14(12): 2145-2153.
Bazanelli,
A.P., Kamimura, M.A., Canziani, M.E.F., Manfredi, S.R. & Cuppari, L. 2013.
Waist circumference as a predictor of adiponectin levels in peritoneal dialysis
patients: A 12-Month follow-up study. Peritoneal Dialysis International 33(2):
182-188.
Chakrabarti,
P., Kim, J.Y., Singh, M., Shin, Y-K., Kim, J., Kumbrink, J., Wu, Y., Lee, M-J.,
Kirsch, K.H., Fried, S.K. & Kandror, K.V. 2013. Insulin inhibits lipolysis
in adipocytes via the evolutionarily conserved mTORC1-Egr1-ATGL-mediated
pathway. Molecular and Cellular Biology 33(18): 3659-3666.
Combs,
T.P., Pajvani, U.B., Berg, A.H., Lin, Y., Jelicks, L.A., Laplante, M.,
Nawrocki, A.R., Rajala, M.W., Parlow, A.F., Cheeseboro, L., Ding, Y.Y.,
Russell, R.G., Lindemann, D., Hartley, A., Baker, G.R., Obici, S., Deshaies,
Y., Ludgate, M., Rossetti, L. & Scherer, P.E. 2004. A transgenic mouse with
a deletion in the collagenous domain of adiponectin displays elevated
circulating adiponectin and improved insulin sensitivity. Endocrinology 145(1):
367-383.
Czech,
M.P., Tencerova, M., Pedersen, D.J. & Aouadi, M. 2013. Insulin signalling
mechanisms for triacylglycerol storage. Diabetologia 56(5): 949-964.
Ghadge,
A.A., Khaire, A.A. & Kuvalekar, A.A. 2018. Adiponectin: A potential
therapeutic target for metabolic syndrome. Cytokine & Growth Factor
Reviews 39: 151-158.
Handjieva-Darlenska,
T. & Boyadjieva, N. 2009. The effect of high-fat diet on plasma ghrelin and
leptin levels in rats. J. Physiol. Biochem. 65(2): 157-164.
Harris,
R.B.S. 2014. Direct and indirect effects of leptin on adipocyte metabolism. Biochimica
et Biophysica Acta (BBA) - Molecular Basis of Disease 1842(3): 414-423.
Izadi,
V., Farabad, E. & Azadbakht, L. 2013. Epidemiologic evidence on serum
adiponectin level and lipid profile. International Journal of Preventive
Medicine 4(2): 133-140.
Jiang,
L., Wang, Q., Yu, Y., Zhao, F., Huang, P., Zeng, R., Qi, R.Z., Li, W. &
Liu, Y. 2009. Leptin contributes to the adaptive responses of mice to high-fat
diet intake through suppressing the lipogenic pathway. PLoS ONE 4(9):
e6884.
Jung,
U.J. & Choi, M.S. 2014. Obesity and its metabolic complications: The role
of adipokines and the relationship between obesity, inflammation, insulin
resistance, dyslipidemia and nonalcoholic fatty liver disease. International
Journal of Molecular Sciences 15(4): 6184-6223.
Karbowska,
J. & Kochan, Z. 2006. Role of adiponectin in the regulation of carbohydrate
and lipid metabolism. Journal of Physiology and Pharmacology 57(Suppl
6): 103-113.
Kelesidis,
T., Kelesidis, I., Chou, S. & Mantzoros, C.S. 2010. Narrative review: The
role of leptin in human physiology: Emerging clinical applications. Annals
of Internal Medicine 152(2): 93-100.
Kim,
J.Y., Ahn, S.V., Yoon, J.H., Koh, S.B., Yoon, J., Yoo, B.S., Lee, S.H., Park,
J.K., Choe, K.H. & Guallar, E. 2013. Prospective study of serum adiponectin
and incident metabolic syndrome: the ARIRANG study. Diabetes Care 36(6):
1547-1553.
Landrier,
J.F., Kasiri, E., Karkeni, E., Mihály, J., Béke, G., Weiss, K., Lucas, R.,
Aydemir, G., Salles, J., Walrand, S., de Lera, A.R. & Rühl, R. 2017.
Reduced adiponectin expression after high-fat diet is associated with selective
up-regulation of ALDH1A1 and further retinoic acid receptor signaling in
adipose tissue. FASEB Journal 31(1): 203-211.
Lee,
B. & Shao, J. 2012. Adiponectin and lipid metabolism in skeletal muscle. Acta
Pharmaceutica Sinica B 2(4): 335-340.
Li,
S. & Li, X. 2016. Leptin in normal physiology and leptin resistance. Science
Bulletin 61(19): 1480-1488.
Lin,
S., Thomas, T.C., Storlien, L.H. & Huang, X.F. 2000. Development of high
fat diet-induced obesity and leptin resistance in C57Bl/6J mice. International
Journal of Obesity 24(5): 639-646.
Matsubara,
M., Maruoka, S. & Katayose, S. 2002. Inverse relationship between plasma
adiponectin and leptin concentrations in normal-weight and obese women. European
Journal of Endocrinology 147(2): 173-180.
Milewicz,
A., Jedrzejuk, D., Dunajska, K. & Lwow, F. 2010. Waist circumference and
serum adiponectin levels in obese and non-obese postmenopausal women. Maturitas 65(3): 272-275.
Morris,
D.L. & Rui, L. 2009. Recent advances in understanding leptin signaling and
leptin resistance. American Journal of Physiology - Endocrinology and
Metabolism 297(6): E1247-1259.
Myers,
M.G. Jr., Leibel, R.L., Seeley, R.J. & Schwartz, M.W. 2010. Obesity and
leptin resistance: Distinguishing cause from effect. Trends in Endocrinology
and Metabolism 21(11): 643-651.
Nawrocki,
A.R., Rajala, M.W., Tomas, E., Pajvani, U.B., Saha, A.K., Trumbauer, M.E.,
Pang, Z., Chen, A.S., Ruderman, N.B., Chen, H., Rossetti, L. & Scherer,
P.E. 2006. Mice lacking adiponectin show decreased hepatic insulin sensitivity
and reduced responsiveness to peroxisome proliferator-activated receptor gamma
agonists. Journal of Biological Chemistry 281(5): 2654-2660.
Qaid,
M.M. & Abdelrahman, M.M. 2016. Role of insulin and other related hormones
in energy metabolism - A review. Cogent Food & Agriculture 2(1):
1267691.
Roberts,
C.K., Hevener, A.L. & Barnard, R.J. 2013. Metabolic syndrome and insulin
resistance: Underlying causes and modification by exercise training. Comprehensive
Physiology 3(1): 1-58.
Srikanthan,
K., Feyh, A., Visweshwar, H., Shapiro, J.I. & Sodhi, K. 2016. Systematic
review of metabolic syndrome biomarkers: A panel for early detection,
management, and risk stratification in the West Virginian population. International
Journal of Medical Sciences 13(1): 25-38.
von
Frankenberg, A.D., Marina, A., Song, X., Callahan, H.S., Kratz, M. &
Utzschneider, K.M. 2017. A high-fat, high-saturated fat diet decreases insulin
sensitivity without changing intra-abdominal fat in weight-stable overweight
and obese adults. Eur. J. Nutr. 56(1): 431-443.
Wong, S.K., Chin, K.Y., Suhaimi, F.H., Ahmad, F. & Ima-
Nirwana, S. 2018a. Effects of metabolic syndrome on bone mineral density,
histomorphometry and remodelling markers in male rats. PLoS ONE 13(2):
e0192416.
Wong,
S.K., Chin, K.Y., Suhaimi, F.H., Ahmad, F. & Ima- Nirwana, S. 2018b. The
effects of palm tocotrienol on metabolic syndrome and bone loss in male rats
induced by high-carbohydrate high-fat diet. Journal of Functional Foods 44:
246-254.
Wong,
S.K., Chin, K.Y., Suhaimi, F.H., Ahmad, F. & Ima- Nirwana, S. 2017a. The
effects of a modified high-carbohydrate high-fat diet on metabolic syndrome
parameters in male rats. Experimental and Clinical Endocrinology &
Diabetes 126(4): 205-212.
Wong,
S.K., Chin, K.Y., Suhaimi, F.H., Ahmad, F., Jamil, N.A. & Ima-Nirwana, S.
2017b. Osteoporosis is associated with metabolic syndrome induced by
high-carbohydrate high-fat diet in a rat model. Biomedicine &
Pharmacotherapy 98: 191-200.
Wong,
S.K., Chin, K.Y., Suhaimi, F.H., Fairus, A. & Ima- Nirwana, S. 2016. Animal
models of metabolic syndrome: A review. Nutrition & Metabolism 13:
65.
Yamamoto,
S., Matsushita, Y., Nakagawa, T., Hayashi, T., Noda, M. & Mizoue, T. 2014.
Circulating adiponectin levels and risk of type 2 diabetes in the Japanese. Nutrition
& Diabetes 4(8): e130.
Yamauchi,
T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S.,
Noda, M., Kita, S., Ueki, K., Eto, K., Akanuma, Y., Froguel, P., Foufelle, F.,
Ferre, P., Carling, D., Kimura, S., Nagai, R., Kahn, B.B. & Kadowaki, T.
2002. Adiponectin stimulates glucose utilization and fatty-acid oxidation by
activating AMP-activated protein kinase. Nature Medicine 8(11):
1288-1295.
*Corresponding author; email:
imasoel@ppukm.ukm.edu.my
|