RNA-seq Based Transcriptome Analysis of the Anti-Obesity Effect of Green Tea Extract Using Zebrafish Obesity Models

Abstract

Green tea is a popular beverage that is rich in polyphenolic compounds such as catechins. Its major content, (-)-epigallocatechin-3-gallate, has been shown to have beneficial effects on several diseases including cancer, metabolic syndrome, cardiovascular diseases, and neurodegenerative diseases. The aim of this study was to assess the anti-obesity effects and the underlying molecular mechanisms of green tea extract (GTE) using zebrafish larva and adult obesity models. We administered 100 μg/mL GTE to zebrafish larvae and performed a short-term obesogenic test. GTE significantly decreased the visceral adipose tissue volume induced by a high-fat diet. Oral administration (250 µg/g body weight/day) of GTE to adult diet-induced obese zebrafish also significantly reduced their visceral adipose tissue volume, with a reduction of plasma triglyceride and total cholesterol levels. To investigate the molecular mechanism underlying the GTE effects, we conducted RNA sequencing using liver tissues of adult zebrafish and found that GTE may ameliorate the obese phenotypes via the activation of Wnt/β-catenin and adenosine monophosphate-activated protein kinase (AMPK) pathway signaling. In addition, the comparative transcriptome analysis revealed that zebrafish and mammals may share a common molecular response to GTE. Our findings suggest that daily consumption of green tea may be beneficial for the prevention and treatment of obesity.

Anti-Obesity Natural Products Tested in Juvenile Zebrafish Obesogenic Tests and Mouse 3T3-L1 Adipogenesis Assays

“…NP08 (GTE) is well-known for its anti-obesity effects through its bioactive constituents such as (-)-epigallocatechin-3-gallate and (-)-epigallocatechin in rodent models [ 21 , 22 , 23 ]. Additionally, several studies have demonstrated the anti-obesity effects of GTE in zebrafish models [ 13 , 16 , 24 ], which are consistent with our results. In humans, continuous ingestion of a GTE significantly reduces body weight and body fat mass [ 25 ], while Huang et al reported that GTE reduced only serum low-density lipoprotein cholesterol, and did not affect body weight or other blood lipids [ 26 ].…”

“…After a 1-day high-fat diet feeding (HFD), Nile Red (NR) staining was performed (day 1). The NR-stained visceral adipose tissue (VAT; red color) was significantly ( p < 0.01) increased in zebrafish fed a HFD compared to those fed a normal diet (ND; Figure 1 b), as shown previously [ 16 ]. Then, the zebrafish were exposed to test the NPs (100 μg/mL) for 48 h, and NR imaging was conducted again (day 3) to compare the NR intensities of the VAT before and after treatment (day 3/day 1).…”

“…ZOT was performed as previously described [ 15 ] with some modifications [ 16 ]. Zebrafish (4–5 week-post-fertilization, standard length ca.…”

“…Tingaud-Sequeira et al first reported that young zebrafish (up to four weeks post fertilization) exposed to boiled chicken eggs showed an increase in visceral adiposity detected by live imaging, named the zebrafish obesogenic test (ZOT) [ 15 ]. Their increased VATs were reduced by short-time exposure to phenylephrine, an alpha-adrenergic agonist [ 15 ], and green tea extracts [ 16 ]. Due to the small size of the young zebrafish, ZOT can be performed in a 6-well plate format; however, there is no systematic analysis to compare the results between ZOT and cell-based assays.…”

Lecithin-Based Dermal Drug Delivery for Anti-Pigmentation Maize Ceramide

“…To remove artefacts (eyes and shadows around the yolk sac) from the images, we set the "analyze particles" parameter with an appropriate pixel size limit. For the Nile Red experiment, the integrated density of each image was measured as Nile Red fluorescent intensity using ImageJ, following the methodology used in a previous study [37].…”