Effect of ecdysterone on the hepatic transcriptome and lipid metabolism in lean and obese Zucker rats

Ecdysteroids are a class of steroid hormones occurring in insects, where they are referred as zooecdysteroids, and in plants, where they are termed phytoecdysteroids. While zooecdysteroids in insects regulate important developmental processes, such as embryogenesis, molting (ecdysis), metamorphosis, reproduction, and diapause, phytoecdysteroids provide protection against invertebrate predators by acting as feeding deterrents and by disrupting critical developmental processes of such invertebrates. The ecdysteroids in insects and plants comprise a great number of different analogues, with 20‐hydroxyecdysone, also called ecdysterone, being the quantitatively dominating biologically active analogue in both, insects and plants. Although phytoecdysteroids are effective toxins or antifeedants towards non-adapted herbivorous invertebrate predators, ecdysteroids are apparently non-toxic to mammals and even have been shown to exert a variety of interesting metabolic actions, such as antiobesity, hypoglycemic and protein-anabolic effects. In the present study aimed to test the hypothesis that ecdysterone causes lipid-lowering effects in obese Zucker rats. To test this hypothesis, two groups of obese Zucker rats were fed a nutrient-adequate diet supplemented without or with 0.05% ecdysterone. This ecdysterone concentration was appropriate to achieve a similar dose of ecdysterone per kg body weight BW as applied in other rodent studies, in which ecdysterone caused either hepatic and plasma lipid-lowering effects or antiobesity effects in different rodent models. In order to decipher the potential lipid-lowering actions of ecdysteroids in Zucker rats, measurements of liver and plasma lipid concentrations and hepatic transcriptome analysis was carried out. To further study if ecdysterone is capable of alleviating the strong lipid-synthetic activity in the liver of obese Zucker rats, the study included also two groups of lean Zucker rats which also received either the ecdysterone-supplemented or the non-supplemented diet. The experiment included 16 male, 25-week-old, homozygous (fa/fa) obese Zucker rats (Crl:ZUC-Leprfa) and 16 male, 25-week-old, heterozygous (fa/+) lean Zucker rats, which were purchased from Charles River (Sulzfeld, Germany). The animals were kept in groups of two animals each under controlled conditions (12-h light:12-h dark, 22 ± 1°C ambient temperature, 50-60 % relative humidity). The lean rats were randomly assigned to two groups [lean control (LC), lean ecdysterone (LE)] of 8 rats each. Also, the obese rats were randomly assigned to two groups [obese control (OC), obese ecdysterone (OE)] of 8 rats each. All groups received the same basal diet, which was sufficient to meet requirements of the rat for maintenance according to National Research Council (NRC) and supplemented (groups LE and OE) or not (groups LC and OC) with 0.5 g ecdysterone (provided from Alibaba, China) per kg diet. For microarray analysis, six liver total RNA samples per group were randomly selected for array hybridization.