Obesity‐associated parameters in the experimental mice recorded at the end of the experiment. HFD C57BL/6J mice were divided into two major groups. One group was continuously fed with HFD, whereas the other group was shifted from HFD to normal diet. Mice of both the groups were orally treated with orlistat (10 mg/kg) or vehicle control on every alternate day for 8 weeks. Their body weight was monitored weekly throughout the study and serum was collected at the end of the experiment. Blood glucose, serum TG, serum cholesterol, serum LDLc and serum free fatty acids were measured. Serum factors including leptin, adiponectin, insulin, resistin, IL‐6 and TNF‐α were estimated by ELISA. Similarly, HFD NOD/SCID mice were treated orally with orlistat or vehicle control on every alternate day for 8 weeks and serum parameters were measured. Parallely, ND C57BL/6J mice were divided into two major groups. One group was orally treated with orlistat or vehicle control on every alternate day before inoculating B16F10 cells. The second group was orally treated with orlistat (10 mg/kg) or vehicle control on every alternate day after 2 days of inoculating B16F10 cells. The treatment was continued for 8 weeks. Their body weight was monitored weekly throughout the study and serum was collected at the end of the experiment for further biochemical analysis. The results are given as means ± standard deviation; *, p < 0.05; **, p < 0.01; ***, p < 0.001; NS, not significant; #, comparison with C57BL/6J HFD‐HFD Ctrl; $, comparison with NOD/SCID HFD‐HFD Ctrl; §, comparison with C57BL/6J ND‐Pre Ctrl; ψ, comparison with C57BL/6J ND‐Post Ctrl.