Back
 CM  Vol.5 No.1 , March 2014
Long-Term Treatment with an Herbal Formula MCC Ameliorates Obesity-Associated Metabolic Dysfunction in High Fat Diet-Induced Obese Mice: A Comparative Study among MCC and Various Combinations of Its Constituents
Abstract: Obesity has been found to be associated with increased incidence of various metabolic disorders. Anti-obesity interventions are therefore urgently needed. An earlier study has demonstrated that treatment with an herbal formula MCC, which comprises the fruit of Momordica charantia (MC), the pericarpium of Citri reticulate (CR) and L-carnitine (CA), reduced the weight gain in high fat diet (HFD)-fed mice. In the present study, we investigated the effect of long-term treatment with MCC (6 g/kg/day × 40 doses) and various combinations of its constituents in HFD-fed female ICR mice. Body weight change was monitored during the course of the experiment. Total and differential adiposity, plasma lipid contents, metabolic enzyme activities and mitochondrial coupling efficiency in skeletal muscle were measured. Glucose homeostasis was also assessed. Results showed that HFD increased the body weight, total and differential adiposity, and plasma lipid contents as well as impaired metabolic status in skeletal muscle and glucose homeostasis. MCC and all combinations of its constituents reduced the weight gain in HFD-fed mice, which was accompanied with an improvement on glucose homeostasis. While MC, CA and CR independently suppressed the HFD-induced weight gain in mice, MC seems to be the most effective in weight reduction, all of which correlated with the induction of mitochondrial uncoupling in skeletal muscle. Only CA and CR, but not MC, significantly reduced the total adiposity and visceral adiposity as well as plasma cholesterol level. However, the two component combinations, MC + CR and MC + CA, decreased the degree of visceral adiposity and plasma cholesterol level, respectively. MCC treatment at 1.5 g/kg (but not a higher dose of 6 g/kg) suppressed visceral adiposity and induced mitochondrial uncoupling in skeletal muscle in HFD-fed mice. The finding suggests that MCC may offer a promising prospect for ameliorating the diet-induced obesity and metabolic disorders in humans.
Cite this paper: Leong, P. , Leung, H. , Wong, H. , Chen, J. , Chan, W. , Ma, C. , Yang, Y. and Ko, K. (2014) Long-Term Treatment with an Herbal Formula MCC Ameliorates Obesity-Associated Metabolic Dysfunction in High Fat Diet-Induced Obese Mice: A Comparative Study among MCC and Various Combinations of Its Constituents. Chinese Medicine, 5, 34-46. doi: 10.4236/cm.2014.51005.
References

[1]   Ahima, R.S. and Lazar, M.A. (2013) The Health Risk of Obesity-Better Metrics Imperative. Science, 341, 856-858.
http://dx.doi.org/10.1126/science.1241244

[2]   Fontana, L.J., Eagon, C., Trujillo, M.E., Scherer, P.E. and Klein, S. (2007) Visceral Fat Adipokine Secretion Is Associated with Systemic Inflammation in Obese Humans. Diabetes, 56, 1010-1013. http://dx.doi.org/10.2337/db06-1656

[3]   Manninen, V., Tenkanen, L., Koskinen, P., Huttunen, J.K., Manttari, M., Heinonen, O.P. and Frick, M.H. (1992) Joint Effects of Serum Triglyceride and LDL Cholesterol and HDL Cholesterol Concentrations on Coronary Heartdisease Risk in the Helsinki Heart Study. Implications for Treatment. Circulation, 85, 37-45.
http://dx.doi.org/10.1161/01.CIR.85.1.37

[4]   Wing, R.R. and Phelan, S. (2005) Long-Term Weight Loss Maintenance. The American Journal of Clinical Nutrition, 82, 222S-225S.

[5]   Caveney, E., Caveney, B.J., Somaratne, R., Turner, J.R. and Gourgiotis, L. (2011) Pharmaceutical Interventions for Obesity: A Public Health Perspective. Diabetes, Obesity and Metabolism, 13, 490-497.
http://dx.doi.org/10.1111/j.1463-1326.2010.01353.x

[6]   Tseng, Y., Cypess, A.M. and Kahn, C.R. (2010) Cellular Bioenergetics as a Target for Obesity Therapy. Nature Reviews Drug Discovery, 9, 465-482. http://dx.doi.org/10.1038/nrd3138

[7]   Thrush, A.B., Dent, R., McPherson, R. and Harper, M.E. (2013) Implications of Mitochondrial Uncoupling in Skeletal Muscle in the Development and Treatment of Obesity. FEBS Journal, 280, 5015-5029.
http://dx.doi.org/10.1111/febs.12399

[8]   Leong, P.K., Leung, H.Y., Wong, H.S., Chen, J., Ma, C.W., Yang, Y. and Ko, K.M. (2013) Long-Term Treatment with an Herbal Formula MCC Reduces the Weight Gain in High Fat Diet-Induced Obese Mice. Chinese Medicine, 4, 63-71.
http://dx.doi.org/10.4236/cm.2013.43010

[9]   Siddiqua, M., Hamid, K., Rashid, M.H.A., Akther, M.S. and Choudhuri, M.S.K. (2010) Changes in Lipid Profile of Rat Plasma after Chronic Administration of Laghobanondo Rosh (LNR)—An Ayurvedic Formulation. Biology and Medicine, 2, 58-63.

[10]   Colberg, S.R., Simoneau, J.A., Thaete, F.L. and Kelley, D.E. (1995) Skeletal Muscle Utilization of Free Fatty Acids in Women with Visceral Obesity. The Journal of Clinical Investigation, 95, 1846-1853.
http://dx.doi.org/10.1172/JCI117864

[11]   Crescenzo, R., Mainieri, D., Solinas, G., Montani, J.P., Seydoux, J., Liverini, G., Iossa, S. and Dulloo, A.G. (2003) Skeletal Muscle Mitochondrial Oxidative Capacity and Uncoupling Protein 3 Are Differently Influenced by Semistarvation and Refeeding. FEBS Letters, 544, 138-142. http://dx.doi.org/10.1016/S0014-5793(03)00491-5

[12]   Wang, C.Y. and Liao, J.K. (2012) A Mouse Model of Diet-Induced Obesity and Insulin Resistance. Methods in Molecular Biology, 821, 421-433. http://dx.doi.org/10.1007/978-1-61779-430-8_27

[13]   Martins, R., Nachbar, R.T., Gorjao, R., Vinolo, M.A., Festuccia, W.T., Lambertucci, R.H., Cury-Boaventura, M.F., Silveira, L.R., Curi, R. and Hirabara, S.M. (2012) Mechanisms Underlying Skeletal Muscle Insulin Resistance Induced by Fatty Acids: Importance of the Mitochondrial Function. Lipids in Health and Disease, 11, 30.
http://dx.doi.org/10.1186/1476-511X-11-30

[14]   Feng, Y., Huang, S.L., Dou, W., Zhang, S., Chen, J.H., Shen, Y., Shen, J.H. and Leng, Y. (2010) Emodin, a Natural Product, Selectively Inhibits 11beta-Hydroxysteroid Dehydrogenase Type 1 and Ameliorates Metabolic Disorder in Diet-Induced Obese Mice. British Journal of Pharmacology, 161, 113-126.
http://dx.doi.org/10.1111/j.1476-5381.2010.00826.x

[15]   Nakamura, M., Ikeda, M., Suzuki, A., Okinaga, S. and Arai, K. (1988) Metabolism of Round Spermatids: Gossypol Induces Uncoupling of Respiratory Chain and Oxidative Phosphorylation. Biology of Reproduction, 39, 771-778.
http://dx.doi.org/10.1095/biolreprod39.4.771

[16]   Kraunsoe, R., Boushel, R., Hansen, C.N., Schjerling, P., Qvortrup, K., Stockel, P., Mikines, K.J. and Dela, F. (2010) Mitochondrial Respiration in Subcutaneous and Visceral Adipose Tissue from Patients with Morbid Obesity. The Journal of Physiology, 588, 2023-2032. http://dx.doi.org/10.1113/jphysiol.2009.184754

[17]   Girard, J. and Lafontan, M. (2008) Impact of Visceral Adipose Tissue on Liver Metabolism and Insulin Resistance. Part II: Visceral Adipose Tissue Production and Liver Metabolism. Diabetes & Metabolism, 34, 439-445.
http://dx.doi.org/10.1016/j.diabet.2008.04.002

[18]   Knight, J.A. (2011) Diseases and Disorders Associated with Excess Body Weight. Annals of Clinical & Laboratory Science, 41, 107-121.

[19]   Caveney, E., Caveney, B.J., Somaratne, R., Turner, J.R. and Gourgiotis, L. (2011) Pharmaceutical Interventions for Obesity: A Public Health Perspective. Diabetes, Obesity and Metabolism, 13, 490-497.
http://dx.doi.org/10.1111/j.1463-1326.2010.01353.x

[20]   Goto, T., Teraminami, A., Lee, J.Y., Ohyama, K., Fu-nakoshi, K., Kim, Y.I., Hirai, S., Uemura, T., Yu, R., Takahashi, N. and Kawada, T. (2012) Tiliroside, a Glycosidic Flavo-Noid, Ameliorates Obesity-Induced Metabolic Disorders via Activation of Adiponectin Signaling Followed by Enhancement of Fatty Acid Oxidation in Liver and Skeletal Muscle in Obese-Diabetic Mice. The Journal of Nutritional Biochemistry, 23, 768-776.
http://dx.doi.org/10.1016/j.jnutbio.2011.04.001

[21]   Costford, S., Gowing, A. and Harper, M.E. (2007) Mitochondrial Uncoupling as a Target in the Treatment of Obesity. Current Opinion in Clinical Nutrition & Metabolic Care, 10, 671-678.
http://dx.doi.org/10.1097/MCO.0b013e3282f0dbe4

[22]   Adjeitey, C.N., Mailloux, R.J., Dekemp, R.A. and Harpe, M.E. (2013) Mitochondrial Uncoupling in Skeletal Muscle by UCP1 Augments Energy Expenditure and Glutathione Content While Mitigating ROS Production. American Journal of Physiology—Endocrinology and Metabolism, 305, E405-E415. http://dx.doi.org/10.1152/ajpendo.00057.2013

 
 
Top