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

 

Diserahkan: 5 Mac 2019/Diterima: 4 Oktober 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

RUJUKAN

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.

 

*Pengarang untuk surat-menyurat; email: imasoel@ppukm.ukm.edu.my

 

 

 

 

 

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