This study investigated the anti-obesity effects of African mango (Irvingia gabonesis, IGOB $131^{TM}$) extract in leptin-deficient obese mice. Experimental groups were treated with two different doses of IGOB $131^{TM}$ (1% and 2% in each AIN93G supplement) for 8 weeks. Treatment of obese mice with both low and high dose of IGOB $131^{TM}$ significantly reduced body weight gain by 10.9% and 13.3%, respectively, compared to control obese mice. Subcutaneous adipose tissue weight of mice was significantly reduced by 18% by low-dose and 23% by high-dose supplementation. This result was supported by micro-CT analysis around the abdominal regions of mice, indicating that the adipose tissue area and volume were significantly reduced by treatment with IGOB $131^{TM}$. Serum levels of triglycerides in the low- and high-dose groups were reduced by 36.5% and 43.8%, respectively, upon treatment with IGOB $131^{TM}$, whereas total cholesterol levels were reduced by 31.8% and 35.4%. Interestingly, the serum LDL level decreased upon treatment with IGOB $131^{TM}$ while the serum level of HDL dramatically increased upon high-dose treatment with IGOB $131^{TM}$, resulting in a significant reduction in the LDL to HDL ratio of 59.2%. These results were supported by the expression levels of enzymes and proteins related to lipid metabolism assessed by real-time PCR. There was a significant increase of in adiponectin expression as well as significant decreases in the expression of FAS, LPL, and lipid regulatory transcription factors such as PPAR-${gamma}$, C/EBP, and SREBP upon both low- and high-dose IGOB $131^{TM}$ treatment. However, there was no statistical difference between low- and high-dose treatments. These results suggest that IGOB $131^{TM}$ is able to regulate the serum lipid profiles by reducing triglyceride and increasing HDL levels as well as regulate expression of lipid metabolic factors, resulting in reduction of a weight gain in leptin-deficient obese mice.