Abstract
Patients with metabolic syndrome are at an increased risk of developing type 2 diabetes and cardiovascular diseases. The principal risk factor for development of metabolic syndrome is obesity, defined as a state of pathological hyperplasia or/and hypertrophy of adipose tissue. The number of mature adipocytes is determined by adipocyte differentiation from preadipocytes. The purpose of the present study is to investigate the effects of curcumin on adipogenesis and the underlying mechanism. To examine cell toxicity of curcumin, 3T3-L1 preadipocytes were treated with 0–50 µM curcumin for 24, 48, or 72 h, then cell viability was measured using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The effect of curcumin on the cell cycle was determined by flow cytometry. Curcumin-induced cell apoptosis was determined by the TUNEL assay and curcumin-induced caspase activation was measured by immunoblotting. The effect of curcumin on adipocyte differentiation was determined by measuring mitotic clonal expansion (MCE), expression of adipogenic transcription factors, and lipid accumulation. Results showed the viability of preadipocytes was significantly decreased by treatment with 30 µM curcumin, a concentration that caused apoptosis in preadipocytes, as assessed by the TUNEL assay, and caused activation of caspases 8, 9, and 3. A non-cytotoxic dose of curcumin (15 µM) inhibited MCE, downregulated the expression of PPARγ and C/EBPα, prevented differentiation medium-induced β-catenin downregulation, and decreased the lipid accumulation in 3T3-L1 adipocytes. In conclusion, our data show that curcumin can induce preadipocyte apoptosis and inhibit adipocyte differentiation, leading to suppression of adipogenesis.
Highlights
Increased visceral fat mass is associated with the development of metabolic disorders, including insulin resistance, dyslipidemia, hypertension, atherosclerosis, and inflammation [1]
Since the cell viability study showed that low dose (≤20 μM) curcumin did not affect the viability of 3T3-L1 preadipocytes (Figure 1A), we investigated the effect of low dose curcumin on adipocyte differentiation. 3T3-L1 preadipocytes were incubated alone or with 5, 10, 15, or 20 μM curcumin for 1 h, adipocyte differentiation was induced in the continued presence or absence of the same concentration of curcumin for 9 days, the intracellular triglyceride content and Oil red O staining were measured to evaluate the efficiency of differentiation
The main finding of this study is that curcumin induced preadipocyte apoptosis in a time- and dose-dependent manner and that this cytotoxic effect involved the activation of both the intrinsic and extrinsic apoptotic pathways
Summary
Increased visceral fat mass is associated with the development of metabolic disorders, including insulin resistance, dyslipidemia, hypertension, atherosclerosis, and inflammation [1]. Obesity is considered as the main cause of metabolic disorders-related diseases, such as cardiovascular disease, hypertension, hyperlipidemia, type 2 diabetes, and cancer [2]. Nutrients 2019, 11, 2307 adipogenesis could be an efficient strategy for preventing the development of metabolic disorder-related diseases [3,4]. L. and has antioxidant [5], anti-inflammation [6,7], and anti-cancer properties [8,9] It has several ameliorating effects on metabolic disorders. A similar inhibition of differentiation of 3T3-L1 adipocytes was reported by Lee et al [15], who found that curcumin can induce apoptosis of MCF-7 breast cancer cells; the apoptotic effect of curcumin on preadipocytes was not investigated. Curcumin is known to have an anti-obesity effect [10,11,12,13,14,15], little is known about the underlying mechanisms of inhibition of adipogenesis
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