Abstract
Obesity is constantly rising into a major health threat worldwide. Activation of brown-like transdifferentiation of white adipocytes (browning) has been proposed as a promising molecular target for obesity treatment. In this study, we investigated the effect of ginsenoside Rb1 (Rb1), a saponin derived from Panax ginseng Meyer, on browning. We used 3T3-L1 murine adipocytes and leptin receptor mutated db/db mice. The lipid accumulation, AMP-activated protein kinase alpha (AMPKα)–related pathways, lipolytic and thermogenic factors were measured after Rb treatment in 3T3-L1 adipocytes. Body weight change and lipolysis–thermogenesis factors were investigated in Rb1-treated db/db mice. Beta 3 adrenergic receptor activation (β3AR) changes were measured in Rb1-treated 3T3-L1 cells with or without β3AR inhibitor L748337 co-treatment. As a result, Rb1 treatment decreased lipid droplet size in 3T3-L1 adipocytes. Rb1 also induced phosphorylations of AMPKα pathway and sirtuins. Moreover, lipases and thermogenic factors such as uncoupling protein 1 were increased by Rb1 treatment. Through these results, we could expect that the non-shivering thermogenesis program can be induced by Rb1. In db/db mice, 6-week injection of Rb1 resulted in decreased inguinal white adipose tissue (iWAT) weight associated with shrunken lipid droplets and increased lipolysis and thermogenesis. The thermogenic effect of Rb1 was possibly due to β3AR, as L748337 pre-treatment abolished the effect of Rb1. In conclusion, we suggest Rb1 as a potential lipolytic and thermogenic therapeutic agent which can be used for obesity treatment.
Highlights
Obesity is rising as a major health issue worldwide, especially in developed countries
Rb1 treatment did not suppress nor increase TG accumulation in 3T3-L1 adipocytes (Figure 2B); the size of lipid droplets was significantly reduced in Rb1-treated cells when compared to differentiated adipocytes (Figures 2C, D)
Park et al reported that Rb1 and another saponin of P. ginseng, ginsenoside Rg1, suppressed TG accumulation in vitro (Park et al, 2008), while Xiong et al showed that the anti-obese effect of Rb1 was effective in vivo as well (Xiong et al, 2010)
Summary
Obesity is rising as a major health issue worldwide, especially in developed countries. As it is a risk factor for type 2 diabetes mellitus (T2DM) and other chronic metabolic disorders, the interest in managing obesity is constantly growing (Hossain et al, 2007). Obesity is a condition defined where excess/abnormal fat accumulation impacts health. As they are the key players in energy homeostasis, the importance of adipose tissues cannot be neglected in the strategy for obesity treatment. The function of WAT is to store the energy in the form of lipids (Luo et al, 2016), while BAT dissipates energy as heat by a process called non-shivering thermogenesis (Yao et al, 2011). Since its identification in the 16th century, intense research on BAT revealed its role in thermogenesis during hibernation (Smith, 1961), and it is appreciated as the main organ for non-shivering thermogenesis (Virtanen, 2016)
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