Immature Citrus reticulata Extract Promotes Browning of Beige Adipocytes in High-Fat Diet-Induced C57BL/6 Mice

Obesity has become a global public health issue. Promoting browning of white adipose tissue (WAT) helps to maintain energy homeostasis. Previous studies have found that citrus fruit exhibits a number of biological activities. Although most citrus fruit drop has been considered agricultural waste, the ability to use it may be desirable. In this study, we investigate the antiobesity effects of immature citrus fruits in high-fat diet (HFD)-fed mice. The main phytochemical components of immature Citrus reticulata in water extraction analyzed by HPLC are synephrine, narirutin, hesperidin, nobiletin, and tangeretin (16.0 +/- 1.08, 4.52 +/- 0.31, 9.14 +/- 0.32, 2.54 +/- 0.07, 1.67 +/- 0.05 mg/g, respectively). Oral administration of 1% immature Citrus reticulata extract (ICRE) for 11 weeks markedly reduced body weight gain, epididymal fat weight, fasting blood glucose, serum triglyceride, and total cholesterol (P < 0.05 for all). In addition, histological analysis revealed that dietary ICRE decreased adipocyte size and hepatic steatosis compared to the HFD group (P < 0.05 for both). Furthermore, we found that mice treated with ICRE have improved cold tolerance during acute cold challenge. These effects were associated with increased expression of uncoupling protein 1 (UCP1) and thermogenic genes in inguinal WAT. Taken together, these results suggest that ICRE can prevent obesity and lipid accumulation through induction of brown-like adipocyte formation.