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

Abstract

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.

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…These data indicate that naringenin may promote the conversion of human WAT to a brown/beige adipose tissue. Similarly, in HFD-obese mouse model, the induction of brown-like adipocyte formation on WAT was described by supplementing the diet with a flavanones-rich extract from Citrus reticulata [ 219 ]. The main phytochemical components of a water extraction of Citrus reticulata in were synephrine, narirutin, hesperidin, nobiletin, and tangeretin.…”

“…Among flavanones, citrus also contain synephrine that is an alkaloid which binds to β 3 AR in adipose tissue promoting lipolysis and thermogenesis [ 220 ]. Dietary supplementation with this citrus extract reduced body weight gain, epididymal fat weight, fasting blood glucose, serum levels of TG and total cholesterol, and lipid accumulation in liver and WAT as well as activated FAO and induced the browning phenotype [ 219 ]. These animals showed increased levels of Ucp1 in the iWAT and an upregulation of Prdm16 , transmembrane protein 26 (Tmem26), cluster of differentiation 137 (CD137), and Cidea [ 219 ].…”

Expression and functional analysis of the nobiletin biosynthesis-related gene CitOMT in citrus fruit

“…Recently, it was reported that flavonoids possess anti-cancer 17 , 18 and anti-allergy 19 activities in in vitro experiments. Moreover, flavonoids have been found to exhibit anti-inflammatory 20 , 21 , anti-obesity 22 , and neuroprotective properties 23 in animal models.…”

miRNAs and Novel Food Compounds Related to the Browning Process

“…Furthermore, a recent study demonstrated a thermogenic effect in brown adipocytes after treatment with bitter orange possible due to AMPK activation [236]. In addition, an in vivo study evaluated the effect of immature citrus fruits (1%) in HFD fed mice for 11 weeks and found an increased expression of Ucp-1 in iWAT, thus suggesting that weight loss might be attributed to the browning process in WAT [237]. In this context, Nishikawa et al [238] analyzed the effect of α-monoglucosyl hesperidin in mice, as a simple glycosidic flavanone, and found a significant decrease in body fat, which may be due to the activation of the browning process in iWAT.…”