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Published on: July 21, 2017
Citrus aurantium flavonoids inhibit adipogenesis through the Akt signaling pathway in 3T3-L1 cells
Gon-Sup Kim1, Hyoung Joon Park, Jong-Hwa Woo
1Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea.
Background:
Obesity is a health hazard that is associated with a number of diseases and metabolic abnormalities, such as type-2 diabetes, hypertension, dyslipidemia, and coronary heart disease. In the current study, we investigated the effects of Citrus aurantium flavonoids (CAF) on the inhibition of adipogenesis and adipocyte differentiation in 3T3-L1 cells.
Methods:
During adipocyte differentiation, 3T3-L1 cells were treated with 0, 10, and 50 μg/ml CAF, and then the mRNA and protein expression of adipogenesis-related genes was assayed. We examined the effect of CAF on level of phosphorylated Akt in 3T3-L1 cells treated with CAF at various concentrations during adipocyte differentiation.
Results:
The insulin-induced expression of C/EBPβ and PPARγ mRNA and protein were significantly down-regulated in a dose-dependent manner following CAF treatment. CAF also dramatically decreased the expression of C/EBPα, which is essential for the acquisition of insulin sensitivity by adipocytes. Moreover, the expression of the aP2 and FAS genes, which are involved in lipid metabolism, decreased dramatically upon treatment with CAF. Interestingly, CAF diminished the insulin-stimulated serine phosphorylation of Akt (Ser473) and GSK3β (Ser9), which may reduce glucose uptake in response to insulin and lipid accumulation. Furthermore, CAF not only inhibited triglyceride accumulation during adipogenesis but also contributed to the lipolysis of adipocytes.
Conclusions:
In the present study, we demonstrate that CAF suppressed adipogenesis in 3T3-L1 adipocytes. Our results indicated that CAF down-regulates the expression of C/EBPβ and subsequently inhibits the activation of PPARγ and C/EBPα. The anti-adipogenic activity of CAF was mediated by the inhibition of Akt activation and GSK3β phosphorylation, which induced the down-regulation of lipid accumulation and lipid metabolizing genes, ultimately inhibiting adipocyte differentiation.
Insights
Citrus aurantium flavonoids (CAF) suppress adipogenesis by down-regulating key gene expression and inhibiting Akt activation. This research shows CAF
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Obesity is a significant health concern linked to type-2 diabetes, hypertension, and cardiovascular disease.
- Investigating natural compounds for anti-obesity effects is crucial for metabolic health.
- Citrus aurantium flavonoids (CAF) were explored for their potential to inhibit adipogenesis.
Purpose of the Study:
- To investigate the effects of Citrus aurantium flavonoids (CAF) on adipogenesis and adipocyte differentiation.
- To determine the molecular mechanisms underlying CAF's impact on key adipogenic genes and signaling pathways.
Main Methods:
- 3T3-L1 cells were treated with varying concentrations of CAF during differentiation.
- mRNA and protein expression of adipogenesis-related genes (C/EBPβ, PPARγ, C/EBPα, aP2, FAS) were analyzed.
- The effect of CAF on Akt and GSK3β phosphorylation was assessed.
Main Results:
- CAF significantly down-regulated C/EBPβ and PPARγ mRNA and protein expression in a dose-dependent manner.
- CAF reduced the expression of C/EBPα, aP2, and FAS, impacting insulin sensitivity and lipid metabolism.
- CAF inhibited insulin-stimulated Akt and GSK3β phosphorylation, reducing lipid accumulation and promoting lipolysis.
Conclusions:
- Citrus aurantium flavonoids (CAF) effectively suppress adipogenesis and adipocyte differentiation in 3T3-L1 cells.
- CAF exerts its anti-adipogenic effects by down-regulating C/EBPβ, PPARγ, and C/EBPα expression.
- Inhibition of Akt activation and GSK3β phosphorylation mediates CAF's impact on lipid metabolism and adipocyte differentiation.

