Raspberry Ketone Increases Both Lipolysis and Fatty Acid Oxidation in 3T3-L1 Adipocytes

Abstract

Raspberry ketone (RK) is a natural phenolic compound of the red raspberry. The dietary administration of RK to male mice has been reported to prevent high-fat diet-induced elevation in body weight and to increase lipolysis in white adipocytes. To elucidate a possible mechanism for the antiobesity action of RK, its effects on the expression and the secretion of adiponectin, lipolysis, and fatty acid oxidation in 3T3-L1 were investigated. Treatment with 10 µM of RK increased lipolysis significantly in differentiated 3T3-L1 cells. An immunoassay showed that RK increased both the expression and the secretion of adiponectin, an adipocytokine mainly expressed and secreted by adipose tissue. In addition, treatment with 10 µM of RK increased the fatty acid oxidation and suppressed lipid accumulation in 3T3-L1 adipocytes. These findings suggest that RK holds great promise as an herbal medicine since its biological activities alter the lipid metabolism in 3T3-L1 adipocytes.

adiponectin - β‐oxidation - lipid metabolism - herbal medicine - raspberry ketone

References

• 1 Hausman D B, DiGirolamo M, Bartness T J, Hausman G J, Martin J R. The biology of white adipocyte proliferation.  Obes Rev. 2001;  2 239-254
• 2 Hu E, Liang P, Spiegelman B M. AdipoQ is a novel adipose-specific gene dysregulated in obesity.  J Biol Chem. 1996;  271 10697-10703
• 3 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley R E, Tataranni P A. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.  J Clin Endocrinol Metab. 2001;  86 1930-1935
• 4 Mullen K L, Smith A C, Junkin K A, Dyck D J. Globular adiponectin resistance develops independently of impaired insulin-stimulated glucose transport in soleus muscle from high-fat-fed rats.  Am J Physiol Endocrinol Metab. 2007;  293 E83-E90
• 5 Wolf G. Adiponectin: a regulator of energy homeostasis.  Nutr Rev. 2003;  61 290-292
• 6 Duntas L H, Popovic V, Panotopoulos G. Adiponectin: novelties in metabolism and hormone regulation.  Nutr Neurosci. 2004;  7 195-200
• 7 Yurie S. The application of raspberry ketone to successful body care.  Fragr J. 2003;  31 38-42
• 8 Harada N, Okajima K, Narimatsu N, Kurihara H, Nakagata N. Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans.  Growth Horm IGF Res. 2008;  18 335-344
• 9 Kawada T, Hagihara K I, Iwai K. Effects of capsaicin on lipid metabolism in rats fed a high fat diet.  J Nutr. 1986;  116 1272-1278
• 10 Carpene C, Galitzky J, Fontana E, Atgie C, Lafontan M, Berlan M. Selective activation of β3-adrenoceptors by octamine: comparative studies in mammalian fat cells.  Naunyn Schmiedebergs Arch Pharmacol. 1999;  359 310-321
• 11 Morimoto C, Satoh Y, Hara M, Inoue S, Tsujita T, Okuda H. Anti-obese action of raspberry ketone.  Life Sci. 2005;  77 194-204
• 12 Kuroyanagi K, Kang M S, Goto T, Hirai S, Ohyama K, Kusudo T, Yu R, Yano M, Sasaki T, Takahashi N, Kawada T. Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production and MCP-1 reduction in 3T3-L1 adipocytes.  Biochem Biophys Res Commun. 2008;  366 219-225
• 13 Rao R K, Baker R D, Baker S S, Gupta A, Holycross M. Oxidant-induced disruption of intestinal epithelial barrier function: role of protein tyrosine phosphorylation.  Am J Physiol Gastrointest Liver Physiol. 1997;  273 G812-G823
• 14 Tateiwa J I, Horiuchi H, Hashimoto K, Yamauchi T, Uemura S. Cation-exchanged montmorillonite-catalyzed facile Friedel-crafts alkylation of hydroxy and methoxy aromatics with 4-hydroxybutan-2-one to produce raspberry ketone and some pharmaceutically active compounds.  J Org Chem. 1994;  59 5901-5904
• 15 Suzuki A, Okamoto S, Lee S, Saito K, Shiuchi T, Minokoshi Y. Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor α gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the α2 form of AMP-activated protein kinase.  Mol Cell Biol. 2007;  27 4317-4327
• 16 Hardie D G, Carling D, Carlson M. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensor of the eukaryotic cell?.  Annu Rev Biochem. 1998;  67 821-855
• 17 Kemp B E, Mitchelhill K I, Stapleton D, Michell B J, Chen Z P, Witters L A. Dealing with energy demand: the AMP-activated protein kinase.  Trends Biochem Sci. 1999;  24 22-25