scholarly journals Effect of Ecdysterone on the Hepatic Transcriptome and Lipid Metabolism in Lean and Obese Zucker Rats

2021 ◽  
Vol 22 (10) ◽  
pp. 5241
Author(s):  
Magdalena J. M. Marschall ◽  
Robert Ringseis ◽  
Denise K. Gessner ◽  
Sarah M. Grundmann ◽  
Erika Most ◽  
...  

Conflicting reports exist with regard to the effect of ecdysterone, the predominating representative of steroid hormones in insects and plants, on hepatic and plasma lipid concentrations in different rodent models of obesity, fatty liver, and diabetes, indicating that the effect is dependent on the rodent model used. Here, the hypothesis was tested for the first time that ecdysterone causes lipid-lowering effects in genetically obese Zucker rats. To test this hypothesis, two groups of male obese Zucker rats (n = 8) were fed a nutrient-adequate diet supplemented without or with 0.5 g ecdysterone per kg diet. To study further 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 male lean Zucker rats (n = 8) which also received either the ecdysterone-supplemented or the non-supplemented diet. While hepatic and plasma concentrations of triglycerides and cholesterol were markedly higher in the obese compared to the lean rats (p < 0.05), hepatic and plasma triglyceride and cholesterol concentrations did not differ between rats of the same genotype fed the diets without or with ecdysterone. In conclusion, the present study clearly shows that ecdysterone supplementation does not exhibit lipid-lowering actions in the liver and plasma of lean and obese Zucker rats.

2019 ◽  
Vol 149 (4) ◽  
pp. 566-577 ◽  
Author(s):  
Denise K Gessner ◽  
Anne Schwarz ◽  
Sandra Meyer ◽  
Gaiping Wen ◽  
Erika Most ◽  
...  

ABSTRACT Background Specific dietary proteins exert strong health-related effects compared with casein. Objective Herein, the hypothesis was tested using screening and conventional biochemical and molecular biological techniques that protein-rich insect meal compared with casein influences metabolic health in hyperlipidemic rats. Methods A 4-wk feeding trial with male, 8-wk-old homozygous obese Zucker rats (n = 36) and male, 8-wk-old heterozygous lean Zucker rats (n = 12) was performed. Obese rats were randomly divided into 3 obese groups (OC, OI50, and OI100) of 12 rats each and lean rats served as a lean control group (LC). LC and OC were fed a control diet with 20% casein as protein source, whereas in OI50 and OI100 50% and 100% of the casein, respectively, was replaced isonitrogenously by insect meal from Tenebrio molitor L. All data were analyzed by 1-factor ANOVA, except transcriptomic data which were analyzed by groupwise comparisons with the OC group. Results Transcript profiling revealed a coordinated inhibition by −17% to −521% and −37% to −859% of genes involved in fatty acid, triacylglycerol (TG), and cholesterol biosynthesis in the livers of OI100 and OI50, respectively, compared with OC (P < 0.05). Enzyme activities of fatty acid synthase, glucose-6 phosphate dehydrogenase, and 3-hydroxy-3-methylglutaryl-coenzyme-A reductase in the liver were 100–150% greater in OC compared with LC, but reduced by 50–60% in OI100 compared with OC (P < 0.05), to the same level as in LC. Liver and plasma concentrations of TG and cholesterol were 250–1000%, 30–800%, and 40–600% higher in OC, OI50, and OI100, respectively, than in LC (P < 0.05), but 40–60% and 20–60% lower in OI100 and OI50, respectively, than in group OC (P < 0.05). Plasma and liver concentrations of homocysteine were 20–30% lower in group OI100 than in group OC (P < 0.05). Conclusion Insect meal exerts pronounced lipid-lowering effects in hyperlipidemic rats and, thus, might be useful for hyperlipidemic individuals.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Martina Cebova ◽  
Radoslava Rehakova ◽  
Michaela Kosutova ◽  
Olga Pechanova

Current treatments for cardiovascular and obesity-associated diseases, such as statin therapy, may be associated with several side effects. Products from food sources with polyphenolic compounds may represent promising agents in the treatment of cardiovascular and metabolic diseases with minimal side effects. Thus, we aimed to study the effect of sesame oil and simvastatin treatment on plasma lipid profile, nitric oxide generation, and oxidative load in obese Zucker rats. 12-week-old male Zucker rats were divided into the control and sesame oil- (1.25 ml/kg/day) treated Zucker lean groups, the control and sesame oil (1.25 ml/kg/day), or simvastatin (15 mg/kg/day) together with sesame oil-treated Zucker fa/fa groups, n=6 in each group. The treatment lasted for 6 weeks. Sesame oil composition and plasma lipid profile were analyzed. Nitric oxide synthase (NOS) activity, endothelial NOS (eNOS), phosphorylated eNOS, and inducible NOS (iNOS) protein expressions were determined in the left ventricle and aorta. Oxidative load, measured as conjugated diene (CD) and thiobarbituric acid reactive substance (TBARS) concentrations, was detected in the liver. Neither sesame oil nor cotreatment with simvastatin affected plasma lipid profile in Zucker fa/fa rats. Sesame oil and similarly cotreatment with simvastatin markedly increased NOS activity and phosphorylated eNOS protein expressions in the left ventricle and aorta of Zucker fa/fa rats. There were no changes in eNOS and iNOS protein expressions within the groups and tissues investigated. Hepatic CD concentration was higher in Zucker fa/fa comparing Zucker lean rats, and sesame oil treatment decreased it significantly. Interestingly, this decrease was not seen after cotreatment with simvastatin. In conclusion, phosphorylation of eNOS and decreased oxidative load may significantly contribute to increase in total NOS activity with potential beneficial properties. Interestingly, simvastatin did not affect NO generation already increased by sesame oil in obese Zucker rats.


2020 ◽  
Vol 150 (10) ◽  
pp. 2707-2715 ◽  
Author(s):  
Oliviero Olivieri ◽  
Giulia Speziali ◽  
Annalisa Castagna ◽  
Patrizia Pattini ◽  
Silvia Udali ◽  
...  

ABSTRACT Background In the settings of primary and secondary prevention for coronary artery disease (CAD), a crucial role is played by some key molecules involved in triglyceride (TG) metabolism, such as ApoCIII. Fatty acid (FA) intake is well recognized as a main determinant of plasma lipids, including plasma TG concentration. Objectives The aim was to investigate the possible relations between the intakes of different FAs, estimated by their plasma concentrations, and circulating amounts of ApoCIII. Methods Plasma samples were obtained from 1370 subjects with or without angiographically demonstrated CAD (mean ± SD age: 60.6 ± 11.0 y; males: 75.8%; BMI: 25.9 ± 4.6 kg/m2; CAD: 73.3%). Plasma lipid, ApoCIII, and FA concentrations were measured. Data were analyzed by regression models adjusted for FAs and other potential confounders, such as sex, age, BMI, diabetes, smoking, and lipid-lowering therapies. The in vitro effects of FAs were tested by incubating HepG2 hepatoma cells with increasing concentrations of selected FAs, and the mRNA and protein contents in the cells were quantified by real-time RT-PCR and LC-MS/MS analyses. Results Among all the analyzed FAs, myristic acid (14:0) showed the most robust correlations with both TGs (R = 0.441, P = 2.6 × 10−66) and ApoCIII (R = 0.327, P = 1.1 × 10−31). By multiple regression analysis, myristic acid was the best predictor of both plasma TG and ApoCIII variability. Plasma TG and ApoCIII concentrations increased progressively at increasing concentrations of myristic acid, independently of CAD diagnosis and gender. Consistent with these data, in the in vitro experiments, an ∼2-fold increase in the expression levels of the ApoCIII mRNA and protein was observed after incubation with 250 μM myristic acid. A weaker effect (∼30% increase) was observed for palmitic acid, whereas incubation with oleic acid did not affect ApoCIII protein or gene expression. Conclusions Plasma myristic acid is associated with increased ApoCIII concentrations in cardiovascular patients. In vitro experiments indicated that myristic acid stimulates ApoCIII expression in HepG2 cells.


1996 ◽  
Vol 7 (12) ◽  
pp. 2604-2615 ◽  
Author(s):  
S Lavaud ◽  
O Michel ◽  
C Sassy-Prigent ◽  
D Heudes ◽  
R Bazin ◽  
...  

Because hyperlipidemia and macrophage influx appear to play a key role in the genesis of renal glomerulosclerosis, this study examined the temporal relationship between hyperlipidemia (triglycerides and cholesterol), mononuclear cell influx, changes in glomerular structure, and expansion of the extracellular matrices in obese Zucker rats, which rapidly develop hyperlipidemia and spontaneous glomerulosclerosis. Lean and obese Zucker rats were fed a standard diet, and were euthanized at 14 days, 1, 3, 6, 9, and 12 months. Plasma lipid, insulin, and creatinine levels were measured, and the presence of inflammatory cells in the glomerulus was assessed by immunohistochemistry on kidney sections. Plasma lipids and insulin and macrophage density were significantly greater in obese than in lean rats as early as 1 month. Computer-assisted image analysis was used to evaluate the glomerular domain surface areas. The morphometric measurements showed that glomeruli of obese rats rapidly became hypertrophied after 3 months, as a result of a very large increase in the mesangial domain. The expression of genes for extracellular matrix components and inhibitors of extracellular matrix proteinases (TIMP-1 and TIMP-2) was monitored in microdissected glomeruli. Reverse transcription-polymerase chain reaction showed increases in mRNA for Type IV collagen and fibronectin and for the two metalloproteinase inhibitors, each of which might participate in this matrix expansion. Thus, the development of hyperlipidemia plus macrophage influx at a very early age may initiate a sequence of events leading to glomerulosclerosis later on.


1983 ◽  
Vol 99 (3) ◽  
pp. 485-490 ◽  
Author(s):  
E. M. Whitaker ◽  
M. A. Shaw ◽  
G. R. Hervey

The plasma oestradiol-17β concentrations of obese and non-obese female Zucker rats have been measured in three phases of the oestrous cycle. The oestradiol concentrations of both phenotypes were similar, and changed normally with the oestrous cycle. The weights of the uteri also changed normally with the cycle. Plasma androgen concentrations in male Zucker rats have also been measured: the mean concentration was slightly but significantly lower in obese rats, and androgen-sensitive tissues were slightly reduced in weight. The oestradiol-17β concentrations in males of both phenotypes were similar. It seems unlikely that deficient plasma concentrations of gonadal hormones cause the infertility of obese rats of either sex.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 987
Author(s):  
Sandra Meyer ◽  
Lea Schäfer ◽  
Julia Röhrig ◽  
Garima Maheshwari ◽  
Erika Most ◽  
...  

The present study tested the hypothesis that the liver lipid-lowering effect of insect meal (IM) is caused by its low methionine concentration. A total of fifty, male obese Zucker rats were randomly assigned to five groups of 10 rats each (casein (C), IM, IM + Met, IM + Cys, and IM + EAA). While group C received a diet with casein, the IM-fed groups received a diet with IM as the protein source. In groups IM + Met, IM + Cys and IM + EAA, the diets were additionally supplemented with methionine, cysteine and essential amino acids (EAA), respectively. Hepatic concentrations of triacylglycerols and cholesterol, and hepatic mRNA levels and activities of lipogenic and cholesterogenic enzymes were markedly lower in the IM-fed groups than in group C (p < 0.05). All of these parameters either did not differ across the IM-fed groups or were only slightly higher in groups IM + Met, IM + Cys and IM+EAA than in the group IM. In conclusion, the results indicate that a difference in the amino acid composition between IM and casein, a low concentration of methionine in IM and a reduced cysteine synthesis secondary to a decreased methionine availability resulting from feeding IM are not causative for the lipid-lowering effect of IM.


2019 ◽  
Vol 493 ◽  
pp. S303
Author(s):  
M. Parra-Robert ◽  
G. Fernández Varo ◽  
E. Casals ◽  
C. Cano ◽  
M. Morales Ruiz ◽  
...  

2002 ◽  
Vol 87 (3) ◽  
pp. 239-245 ◽  
Author(s):  
Timo Vaskonen ◽  
Eero Mervaala ◽  
Ville Sumuvuori ◽  
Tuulikki Seppänen-Laakso ◽  
Heikki Karppanen

Ca may interfere with fat and cholesterol metabolism through formation of insoluble soaps with fatty and bile acids in the intestine. In the present study, we examined the effects of different dietary Ca levels on the serum lipid profile and cholesterol metabolism in obese Zucker rats fed a low-fat diet. We also tested whether dietary Ca interfered with the lipid-lowering effects of a pine oil-derived plant sterol mixture. Increase in dietary Ca intake from 0·2 to 0·8 %, and further to 2·1 % (w/w) dose-dependently decreased serum total cholesterol (r -0·565, P=0·002, n 27), LDL-cholesterol (r -0·538, P=0·006, n 25), and triacylglycerol (r -0·484, P=0·014, n 25) concentrations, and increased HDL-cholesterol (r 0·478, P=0·016, n 25) and HDL : LDL cholesterol (r 0·672, P<0·001, n 25) in rats fed a 1 % cholesterol diet. Analysis of serum campesterol : cholesterol and sitosterol : cholesterol suggested that Ca dose-dependently increased intestinal cholesterol absorption (r 0·913, P<0·001, n 18), whereas serum desmosterol : cholesterol and lathosterol : cholesterol indicated that Ca dose-dependently increased endogenous cholesterol synthesis (r 0·691, P=0·003, n 18). Therefore, the decrease of serum LDL-cholesterol appeared to be due to Ca-induced increase in the conversion of cholesterol to bile acids. The increase in Ca intake did not interfere with the beneficial effects of plant sterols on serum total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. The high-Ca diet with plant sterol supplementation further increased the HDL-cholesterol concentration and HDL : LDL cholesterol. The present findings indicate that the beneficial effects of dietary Ca on the serum lipid profile during a low-fat diet are dose-dependent, and resemble those of bile acid sequestrants. Increased dietary Ca did not impede the lipid-lowering effects of natural plant sterols.


Nanoscale ◽  
2021 ◽  
Author(s):  
Marina Parra-Robert ◽  
Muling Zeng ◽  
Ying Shu ◽  
Guillermo Fernández-Varo ◽  
Meritxell Perramón ◽  
...  

Addressing the metabolic profile associated with obesity is still unsolved. Mesoporous silica coated CeO2 nanozymes, with high stability and maximized antioxidant activity, induce long-term improvement of the metabolic profile in obese Zucker rats.


1996 ◽  
Vol 148 (2) ◽  
pp. 347-353 ◽  
Author(s):  
L Cattaneo ◽  
V De Gennaro Colonna ◽  
M Zoli ◽  
E E Müller ◽  
D Cocchi

Abstract Obesity is coupled to several disturbances of the endocrine axes. It has previously been shown that genetically obese Zucker male rats have an impaired secretion of growth hormone (GH), probably originating from a primary reduction of hypothalamic GH-releasing hormone (GHRH) function and resulting in a decrease of GH gene expression and release. We sought to evaluate the somatotropic function in another model of experimental obesity. Normal male Sprague-Dawley rats were fed an energy-rich highly palatable diet for 7 months until they reached body weights overlapping those reported for obese Zucker rats. They were then evaluated for different indices of the hypothalamo–pituitary–somatomedin-C (IGF-I) axis. At the end of the overfeeding period, rats were divided into overtly obese (obese group) and overweight (overweight group) rats according to the degree of overweight and the Obesity Lee Index, while rats fed ad libitum with the standard pellet chow served as controls. Acute administration of a supramaximal dose of GHRH (2 μg/rat i.v.) elicited a significantly (at least P<0·05) lower plasma GH rise in the overweight and obese groups compared with the controls although no difference was seen in the pituitary GH content and gene expression and plasma concentrations of free IGF-I in the two experimental groups vs the controls. In addition, evaluation of hypothalamic GHRH and somatostatin mRNAs (slot-blot hybridization) did not show any significant differences between the three groups. Of the different metabolic indices investigated, plasma glucose and insulin concentrations were significantly (P<0·01) higher in the obese than in the overweight and control groups. A sharp decrease in plasma testosterone levels, together with a reduction in testis weight, was seen in both groups of rats fed the palatable diet compared with the controls. These findings underline the 'peripheral' feature of the hyposomatotropinism of rats chronically fed an energy-rich diet, and may account for the reversibility of the GH impairment in many obese subjects once a normal body weight has been restored. Moreover, the peripherally-driven hyposomatotropinism of these rats is in sharp contrast with the hypothalamic-driven GH secretory impairment of the obese Zucker rats. Journal of Endocrinology (1996) 148, 347–353


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