Objective An imbalance between dietary energy intake and energy expenditure may result in body fat gain or obesity. Increasing resting energy expenditure (REE) is an attractive strategy for managing body fat gain. The objective of the current study was to generate proof-of-concept data on a synergistic composition (LN19183) of Citrus aurantifolia fruit rind (CA) and Theobroma cacao seed (TC) extracts to increase REE and reduce body fat gain in a high-fat diet (HFD)–fed rats. Method In in vitro cell-based experiments, CA, TC, or LN19183 were tested for fibroblast growth factor 21 (FGF-21) production from 3T3-L1 mouse adipocytes. Uncoupling protein 1 (UCP-1) and beta3-adrenergic receptor (β3-AR) protein expressions in LN19183-treated 3T3-L1 lysates were also tested. The 56-day in vivo study in male Sprague Dawley (SD) rats (age: 12–14 weeks; body weight [b.w.]: 115–197 g) contained 2 phases of 28 days each of induction and supplementation. Seven rats received a regular rodent diet (RD) over 56 days. In the induction phase, 21 rats received HFD; in the supplementation phase, the obese rats (n = 7) received either HFD alone or in concurrence with a daily oral dose of either 100 or 250 mg/kg b.w. of LN19183 for 28 days. Results In 3T3-L1 adipocytes, LN19183 synergistically increased FGF-21 production and dose-dependently increased β3-AR and UCP-1 protein expression. In HFD-fed rats, both doses of LN19183 supplementation significantly (p < 0.05) decreased the body weight gain, total fat mass, and liver weight and increased (p < 0.05) REE. High-dose LN19183 also significantly (p < 0.05) increased fat oxidation and UCP-1 protein expression in white fat tissue and reduced liver triglyceride (TG) level. LN19183-supplemented groups substantially reduced serum TG and glucose levels compared to the HFD rats. Conclusions LN19183 reduces body fat mass and weight gain via increased REE and fat oxidation in HFD-fed obese rats.