Abstract
Objectives
Rottlerin (mallotoxin) is a polyphenolic compound in Mallotus philippensis. The anti-tumor, anti-inflammation, and mitochondrial uncoupling regulation effects of rottlerin have been known. However, the anti-obesity effect was not reported yet. Thus, we hypothesized that rottlerin would suppress body fat accumulation in obesity-induced mice.
Methods
Five-week-old male C57BL/6 mice were fed a high-fat diet (HFD) (60% kcal from fat) ad libitum for 8 weeks. Mice were randomly assigned to five groups as follows: 1) normal diet (18% kcal from fat), 2) negative control (60% kcal from fat), 3) rottlerin 10 (HFD + rottlerin 10 mg/kg bw), 4) rottlerin 20 (HFD + 20 mg/kg bw), 5) positive control (HFD + metformin 150 mg/kg bw). Rottlerin was daily supplemented by oral gavage. Body weight and feed intake were measured each week.
Results
Body weight and weight gain were reduced in rottlerin 20 compared to the control (P < 0.001). Body fat mass was also significantly decreased by rottlerin (P < 0.05). Total feed intake and lean mass were similar among HFD groups. Furthermore, energy expenditure was dose-dependently facilitated by rottlerin. RNA-sequencing results supported these findings that rottlerin 20 up-regulated fatty acid beta-oxidation, heat generation, and brown cell differentiation in white-adipose tissues. Rottlerin promoted a catabolic pathway such as lipolysis, thermogenesis, and oxidation in white adipose tissues. Moreover, non-esterified fatty acid levels were decreased by rottlerin (P < 0.05), and hepatic triglyceride contents tended to decline in rottlerin 20 without hepatotoxicity. Non-shivering thermogenesis enzymes, PRDM16 (P = 0.06) and UCP1 (P < 0.01), were stimulated by rottlerin.
Conclusions
Rottlerin supplementation altered body adiposity accumulation via enhancing fat utilization, lipolysis, and thermogenesis in obese mice. We suggest that rottlerin is a potent nutraceutical for anti-obesity.
Funding Sources
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; MSIT).