Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients

Abstract

Berberine is known to inhibit the differentiation of 3T3-L1 cells in vitro, improve glycemic control, and attenuate dyslipidemia in clinical study. The aim of this study was to investigate the effects of berberine on preadipocytes isolated from human omental fat and in metabolic syndrome patients treated with berberine for 3 months. We have shown that treatment with 10 μM berberine resulted in a major inhibition of human preadipocyte differentiation and leptin and adiponectin secretion accompanied by downregulation of PPARγ2, C/EBPα, adiponectin, and leptin mRNA expression. After 3 months of treatment, metabolic syndrome patients showed decrease in their BMI (31.5 ± 3.6 versus 27.4 ± 2.4 kg/m(2)) and leptin levels (8.01 versus 5.12 μg/L), as well as leptin/adiponectin ratio and HOMA-IR. These results suggest that berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokine profile in human preadipocytes and metabolic syndrome patients.

Figure 1

Representative phase-contrast images of human omental preadipocytes in primary culture and differentiated preadipocytes. (a) Human omental preadipocytes in primary culture, (b) mature adipocytes induced from preadipocyte differentiation, and (c) mature adipocytes stained with Oil-Red-O, ×200.

Figure 2

Effect of berberine on human preadipocyte proliferation. Cells were cultured in growth medium with different concentrations of berberine for 1, 2, and 3 days. At each culture time point, proliferation capacity was determined by MTT assay. Values are expressed as percentage of the untreated controls and represent the mean ± SEM of the three separate experiments in eight replicates. *P < 0.05, compared to control at each time point.

Figure 3

Effect of berberine on human preadipocyte differentiation. Cells differentiated in the absence or presence of different concentrations of berberine over 16 days. The degree of differentiation was determined by Oil-Red-O staining. (a) Photomicrographs representing cells maintained in different concentrations of berberine: (A) control, (B) 0.1 μM berberine, (C) 1 μM berberine, (D) 10 μM berberine, ×100. (b) Absorbance value representing the mean ± SEM of the three separate experiments in six replicates. *P < 0.01, comparison between berberine-treated groups and control group, ^† P < 0.05, comparison among berberine-treated groups.

Figure 4

Effect of berberine on PPARγ2, lipoprotein lipase, C/EBPα, leptin, and adiponectin mRNA expression in differentiated preadipocytes analyzed using RT-PCR. (a) Digital photos of PCR products in agarose gel. Lane 1: control group, lane 2: 10 μM berberine, lane M: DNA markers. (b) Results are expressed as the ratio between the intensity of band corresponding to target gene versus that to β-actin, representing the mean ± SEM of the three separate experiments in triplicate. *P < 0.05, compared to control.

Figure 5

Effect of berberine on leptin and adiponectin secretion during the process of preadipocyte differentiation. Results represent the mean values of the three separate experiments in triplicate.