Effects of Capsaicin on Induction of Apoptosis and Inhibition
of Adipogenesis in 3T3-L1 Cells
CHIN-LIN HSU AND GOW-CHIN YEN*
Department of Food Science and Biotechnology, National Chung Hsing University,
250 Kuokuang Road, Taichung 40227, Taiwan
Currently, at the beginning of the 21st century, obesity has become the leading metabolic disease in
the world. It is a serious health problem in industrialized countries. Previous research has suggested
that decreased preadipocyte differentiation and proliferation and decreased lipogenesis are mech-
anisms to reduce obesity. In the present study, the effects of capsaicin on the induction of apoptosis
and inhibition of lipid accumulation in 3T3-L1 preadipocytes and adipocytes were investigated. The
results demonstrated that capsaicin decreased cell population growth of 3T3-L1 preadipocytes,
assessed with the MTT assay. Flow cytometric analysis of 3T3-L1 preadipocytes exposed to capsaicin
showed that apoptotic cells increased in a time- and dose-dependent manner. Treatment with capsaicin
decreased the number of normal cells and increased the number of early apoptotic and late apoptotic
cells in a dose-dependent manner. The treatment of cells with capsaicin caused the loss of
mitochondria membrane potential (∆Ψm). The induction of apoptosis in 3T3-L1 preadipocytes by
capsaicin was mediated through the activation of caspase-3, Bax, and Bak, and then through the
cleavage of PARP and the down-regulation of Bcl-2. Moreover, capsaicin significantly decreased the
amount of intracellular triglycerides and glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-
L1 adipocytes. Capsaicin also inhibited the expression of PPARγ, C/EBPR, and leptin, but induced
up-regulation of adiponectin at the protein level. These results demonstrate that capsaicin efficiently
induces apoptosis and inhibits adipogenesis in 3T3-L1 preadipocytes and adipocytes.
KEYWORDS: Capsaicin; adipogenesis; 3T3-L1 cells; apoptosis; protein expression
Obesity is an important topic in the realm of public health
and preventive medicine, because it is considered to be a risk
factor associated with the genesis or development of various
diseases, including coronary heart disease, hypertension, type
2 diabetes mellitus, cancer, respiratory complications, and
osteoarthritis (1). Currently, at the beginning of the 21st century,
obesity has become the leading metabolic disease in the world
(2). Recent reports have proposed mechanisms to reduce obesity,
including decreased energy/food intake and increased energy
expenditure, decreased preadipocyte differentiation and prolif-
eration, decreased lipogenesis, and increased lipolysis and fat
oxidation (3). The preadipocytes play a key role by differentiat-
ing into mature adipocytes and increasing fat mass. Obesity is
characterized at the cell biological level by an increase in the
number and size of adipocytes differentiated from fibroblastic
preadipocytes in adipose tissue (4). Hausman et al. (5) indicated
that adipogenesis is a process wherein the preadipocytes
differentiate into adipocytes. MacDougald and Mandrup (6) also
indicated the major differentiation programmed is coordinated
by several positive and negative adipogenic molecules, including
a variety of growth factors, cytokines, and hormones.
Capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide) is a
major pungent ingredient in red pepper that is widely used as
a spice (7). The pepper is a potent analgesic, anti-inflammatory
(8), and causes desensitization to different chemical irritants
upon long-term treatment. Capsaicin has been reported to
decrease energy intake (9), decrease the adipose tissue weight,
and decrease the serum triacylglycerol content by enhancing
energy metabolism (10). Capsaicin inhibits the growth of various
immortalized and malignant cells (11) and induces apoptosis
in transformed cells (12). The chemical structure of capsaicin
is shown in Figure 1. Cell apoptosis is important for destruction
of undesired cells during development and homeostasis of
multicellular organisms and is characterized by distinct mor-
phological changes such as plasma membrane blebbing, cell
shrinkage, depolarization of mitochondria, chromatin condensa-
tion, and DNA fragmentation (13). There are two main pathways
leading to apoptosis. The first of these depends on the
participation of mitochondria, and the second is involved in the
interaction of a death receptor with its ligand. Many proteins
are known to be involved in the process of programmed cell
death. Caspase are a family of cysteine proteases that are
activated during the execution phase of the cell apoptotic process
* Author to whom correspondence should be addressed. Phone: 886-
4-22879755. Fax: 886-4-22854378. E-mail: firstname.lastname@example.org.
J. Agric. Food Chem. 2007, 55, 1730−1736
10.1021/jf062912b CCC: $37.00 © 2007 American Chemical Society
Published on Web 02/13/2007
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Received for review October 11, 2006. Revised December 29, 2006.
Accepted January 8, 2007. This research work was partially supported
by the Department of Health, Taiwan, ROC, under Grant DOH95-
J. Agric. Food Chem., Vol. 55, No. 5, 2007Hsu and Yen