Abstract
This study examined the anti-obesity effect and mechanism of action of blueberry peel extracts (BPE) in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. The levels of lipid accumulation were measured, along with the changes in the expression of genes and proteins associated with adipocyte differentiation in 3T3-L1 cells. Evidenced by Oil-red O staining and triglyceride assay, BPE dose-dependently inhibited lipid accumulation at concentrations of 0, 50, and 200 µg/ml. BPE decreased the expression of the key adipocyte differentiation regulator C/EBPβ, as well as the C/EBPα and PPARγ genes, during the differentiation of preadipocytes into adipocytes. Moreover, BPE down-regulated adipocyte-specific genes such as aP2 and FAS compared with control adipocytes. The specific mechanism mediating the effects of BP revealed that insulin-stimulated phosphorylation of Akt was strongly decreased, and its downstream substrate, phospho-GSK3β, was downregulated by BPE treatment in 3T3-L1 cells. Together, these data indicated that BP exerted anti-adipogenic activity by inhibiting the expression of PPARγ and C/EBPβ and the Akt signaling pathway in 3T3-L1 adipocytes. Next, we investigated whether BP extracts attenuated HFD-induced obesity in rats. Oral administration of BPE reduced HFD-induced body weight gain significantly without affecting food intake. The epididymal or perirenal adipose tissue weights were lower in rats on an HFD plus BPE compared with the tissue weights of HFD-induced obese rats. Total cholesterol and triglyceride levels in the rats fed BPE were modestly reduced, and the HDL-cholesterol level was significantly increased in HFD plus BP-fed rats compared with those of HFD-fed rats. Taken together, these results demonstrated an inhibitory effect of BP on adipogenesis through the down-regulation of C/EBPβ, C/EBPα, and PPARγ and the reduction of the phospho-Akt adipogenic factor in 3T3-L1 cells. Moreover, BPE reduced body weight gain and inhibited fat accumulation in an HFD-induced animal model of obesity.
Highlights
Obesity is one of the greatest public health problems and major risk factors for serious metabolic diseases and significantly increases the risk of premature death
We evaluated the effects of Blueberry peel (BP) on adipocyte differentiation as well as its inhibitory mechanisms on adipogenesis in 3T3-L1 cells and anti-obesity activities in high-fat diet (HFD)-induced obese rats
CCAAT/enhancer binding protein-beta (C/EBPb) was induced immediately after differentiation, and C/EBPa and peroxisome proliferator-activated receptor gamma (PPARc) are master regulators of adipogenesis; their maintenance is critical to the progression of the final stages of adipocyte differentiation [6,27]
Summary
Obesity is one of the greatest public health problems and major risk factors for serious metabolic diseases and significantly increases the risk of premature death. Adipocyte differentiation depends upon the coordinated regulation of gene expression Adipogenic transcription factors such as of the CCAAT/enhancer binding protein-beta (C/EBPb), nuclear receptor peroxisome proliferator-activated receptor gamma (PPARc), and CCAAT/enhancer binding protein-alpha (C/ EBPa) play a key role in the complex transcriptional cascade that occurs during adipogenesis [5]. C/EBPb is induced immediately after differentiation, whereas C/EBPa and PPARc are expressed much later [5,6] They are necessary for the expression of adipocyte-specific genes, such as adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), leptin, adiponectin and fatty acid synthase (FAS) [5,7], which lead to morphological changes and lipid accumulation within the cells. Insulin signaling activates Akt through PI3K and induces serine/ threonine phosphorylation of downstream target, GSK3b, which phosphorylates C/EBPb, C/EBPa, and glycogen synthesis (GS) [11,12]
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