Abstract
The alteration of white adipose tissue (WAT) “browning”, a change of white into beige fat, has been considered as a new therapeutic strategy to treat obesity. In this study, we investigated the browning effect of black raspberry (Rubus coreanus Miquel) using in vitro and in vivo models. Black raspberry water extract (BRWE) treatment inhibited lipid accumulation in human mesenchymal stem cells (hMSCs) and zebrafish. To evaluate the thermogenic activity, BRWE was orally administered for 2 weeks, and then, the mice were placed in a 4 °C environment. As a result, BRWE treatment increased rectal temperature and inguinal WAT (iWAT) thermogenesis by inducing the expression of beige fat specific markers such as PR domain zinc-finger protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and t-box protein 1 (TBX1) in cold-exposed mice. Furthermore, ellagic acid (EA), a constituent of BRWE, markedly promoted beige specific markers: UCP1, PGC1α, TBX1, and nuclear respiratory factor 1 in beige differentiation media (DM)-induced 3T3-L1 adipocytes. Our findings indicate that BRWE can promote beige differentiation/activation, and EA is the active compound responsible for such effect. Thus, we suggest the nature-derived agents BRWE and EA as potential agents for obesity treatment.
Highlights
Obesity, associated with a caloric imbalance in the body, has become an international public health problem worldwide [1]
Cytotoxicity of Black raspberry water extract (BRWE) in human mesenchymal stem cells (hMSCs) was confirmed in our previous report [11]; we chose the concentrations of 5 and 10 μg·mL−1 for the treatment of the pre-adipocytes
By immunoblotting assays, we observed a noticeable decrease of the levels of PPARγ and C/EBPα reduction in BRWE-treated white adipocytes (Figure 1D,E)
Summary
Obesity, associated with a caloric imbalance in the body, has become an international public health problem worldwide [1]. The etiological relationship between obesity and metabolic diseases has been established by various experimental and clinical studies [2]. The massive expansion of white adipose tissue (WAT), a striking feature in obesity, resulted in an increased risk of chronic disorders including type 2 diabetes, heart diseases, systemic hypertension, hyperlipidemia, and arteriosclerosis [3]. Human adipose tissue can be divided into two subsets: brown adipose tissue (BAT) and WAT. The WAT is used for energy storage while the BAT is involved in energy dissipation through heat generation from free fatty acids (FFAs) [4]. Thermogenic ability of BAT depends on a large number of mitochondria and a high level of uncoupling protein 1 (UCP1). The UCP1 has been known as Nutrients 2019, 11, 2164; doi:10.3390/nu11092164 www.mdpi.com/journal/nutrients
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