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Chokeberry Extract and Its Active Polyphenols Suppress Adipogenesis in 3T3-L1 Adipocytes and Modulates Fat Accumulation and Insulin Resistance in Diet-Induced Obese Mice

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Chokeberry Extract and Its Active Polyphenols Suppress Adipogenesis in 3T3-L1 Adipocytes and Modulates Fat Accumulation and Insulin Resistance in Diet-Induced Obese Mice

Na-Hyun Kim et al. Nutrients.

Abstract

Berries of Aronia melanocarpa (chokeberry) are known to be a rich source of biologically active polyphenols. In the present study, the effects of seven anti-adipogenic polyphenolic phytochemicals isolated from A. melanocarpa methanol extract on adipogenic transcription factors were investigated. Amygdalin and prunasin were found to inhibit 3T3-L1 adipocyte differentiation by suppressing the expressions of PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer binding protein α), SREBP1c (sterol regulatory element binding protein 1c), FAS (fatty acid synthase), and aP2 (adipocyte fatty-acid⁻binding protein). A. melanocarpa extract-treated (100 or 200 mg/kg/day on body weight) high fat diet (HFD)-induced obese mice showed significant decreases in body weight, serum triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) levels and improved insulin sensitivity as compared with HFD controls. This research shows A. melanocarpa extract is potentially beneficial for the suppression of HFD-induced obesity.

Keywords: Aronia melanocarpa; adipogenic transcription factor; anti-adipogenesis; diet-induced obesity; insulin resistance; polyphenols.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Chemical structure of compounds isolated from Aronia melanocarpa (Chokeberries). 1: chlorogenic acid, 2: amygdalin, 3: 1-(3,4-dihydroxycinnamoyl cyclopenta-2,3-diol, 4: methyl 3-O-caffeoylquinic acid, 5: cyanidin-3-glucoside, 6: prunasin, and 7: cyanidin-3-xyloside.
Figure 2
Figure 2
Suppression of the differentiation of 3T3-L1 preadipocytes by compounds 17 isolated from A. melanocarpa extract. (a) Cytotoxic effects compounds 17 on 3T3-L1 cells. Cells were exposed to the compounds at 10 μM. Results are the means ± SDs of triplicate experiments. (b) Anti-adipogenic effects of compounds 17 in 3T3-L1 cells. Cells were exposed to differentiation cocktail (0.5 mM IBMX, 10 μg/mL insulin, and 1 μM dexamethasone) in the presence or absence of samples at a concentration of 10 μM for eight days. Morphological changes were detected under a microscope and lipid accumulations were assessed using Nile Red fluorescent reagent. Results are the means ± SDs of triplicate experiments.
Figure 3
Figure 3
Inhibitions of the mRNA expressions of PPARγ (a), SREBP1 (b), C/EBPα (c), FAS (d), LPL (e), and aP2 (f) by compounds 17 in differentiated 3T3-L1 cells. Cells were exposed to differentiation cocktail (0.5 mM IBMX, 10 μg/mL insulin, and 1 μM dexamethasone) in the presence or absence compounds 17 at a concentration of 10 μM for eight days. Results are expressed as means ± SDs, n = 3 per group. * p < 0.05, ** p < 0.01, and *** p < 0.001 versus treatment naïve controls.
Figure 4
Figure 4
Effects of A. melanocarpa extract on body weights (a). Perirenal and perigonal fat masses (b) of mice fed a HFD for eight weeks. Results are presented as means ± SDs (n = 12). Weights in the A. melanocarpa-treated and Orlistat-treated HFD groups were significantly lower than those in the HFD group; ### p < 0.001 vs. the ND group; * p < 0.05 and ** p < 0.01 vs. the VC group. Group I (ND), normal diet group; Group II (VC), high-fat diet group; Group III (PC), Orlistat-treated group; and Group IV (T1), 100 mg/kg b.w. A. melanocarpa extract-treated group; Group V (T2), 200 mg/kg b.w. A. melanocarpa extract-treated group.
Figure 5
Figure 5
Effect of A. melanocarpa extract on serum lipid levels in HFD-induced obese mice. (a) Serum triglyceride (TG) levels. (b) Serum total cholesterol (TC) levels. (c) Serum low-density lipoprotein cholesterol (LDL) levels. (d) Serum high-density lipoprotein cholesterol (HDL) levels. Results are presented as means ± SDs (n = 12); # p < 0.05 and ### p < 0.001 vs. the ND group. Group I (ND), normal diet group; Group II (VC), high-fat diet group; Group III (PC), Orlistat-treated group; and Group IV (T1), 100 mg/kg b.w. A. melanocarpa extract-treated group; Group V (T2), 200 mg/kg b.w. A. melanocarpa extract-treated group.
Figure 6
Figure 6
Effect of A. melanocarpa extract on oral glucose tolerance test (OGTT) and the respective AUC (a) and intraperitoneal insulin tolerance test (IPITT) and the respective AUC (b). Results are presented as means ± SDs (n = 12); ### p < 0.001 vs. the ND group; * p < 0.05 and *** p < 0.001 vs. the VC group. Group I (ND), normal diet group; Group II (VC), high-fat diet group; Group III (PC), Orlistat-treated group; and Group IV (T1), 100 mg/kg b.w. A. melanocarpa extract-treated group; Group V (T2), 200 mg/kg b.w. A. melanocarpa extract-treated group.

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