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Synergistic Effect of Feeding Time and Diet on Hepatic Steatosis and Gene Expression in Male Wistar Rats.

ABSTRACT: OBJECTIVE:Eating out of phase with the endogenous biological clock alters clock and metabolic gene expression in rodents and can induce obesity and type 2 diabetes mellitus. Diet composition can also affect clock gene expression. This study assessed the combined effect of diet composition and feeding time on (1) body composition, (2) energy balance, and (3) circadian expression of hepatic clock and metabolic genes. METHODS:Male Wistar rats were fed a chow or a free-choice high-fat, high-sugar (fcHFHS) diet, either ad libitum or with food access restricted to either the light or dark period. Body weight, adiposity, and hepatic fat accumulation as well as hepatic clock and metabolic mRNA expression were measured after 5 weeks of the diet. Energy expenditure was measured using calorimetric cages. RESULTS:Animals with access to the fcHFHS diet only during the light period showed more hepatic fat accumulation than fcHFHS dark-fed animals despite less calories consumed. In contrast, within the chow-fed groups, light-fed animals showed the lowest hepatic fat content, but they also showed the lowest caloric intake. Locomotor activity and heat production followed feeding times, except in the fcHFHS light-fed group. Hepatic clock and metabolic gene expression rhythms also followed timing of food intake. Yet, in the fcHFHS light-fed animals, clock gene expression appeared 3 hours advanced compared with chow light-fed animals, an effect not observed in the fcHFHS dark-fed animals. CONCLUSIONS:An fcHFHS diet consumed in the light period promotes hepatic fat accumulation and advances clock gene expression in male Wistar rats, likely because of a mismatch between energy intake and expenditure.

SUBMITTER: Oosterman JE

PROVIDER: S-EPMC7496547 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Synergistic Effect of Feeding Time and Diet on Hepatic Steatosis and Gene Expression in Male Wistar Rats.

Oosterman Johanneke E JE Koekkoek Laura L LL Foppen Ewout E Unmehopa Unga A UA Eggels Leslie L Verheij Joanne J Fliers Eric E la Fleur Susanne E SE Kalsbeek Andries A

Obesity (Silver Spring, Md.) 20200531

<h4>Objective</h4>Eating out of phase with the endogenous biological clock alters clock and metabolic gene expression in rodents and can induce obesity and type 2 diabetes mellitus. Diet composition can also affect clock gene expression. This study assessed the combined effect of diet composition and feeding time on (1) body composition, (2) energy balance, and (3) circadian expression of hepatic clock and metabolic genes.<h4>Methods</h4>Male Wistar rats were fed a chow or a free-choice high-fat ...[more]

PMID: 32475046

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Project description:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) caused by liver lipid dysregulation is linked to obesity. Somatostatin (SST) and its analogs have been used to treat pediatric hypothalamic obesity. However, the application of such drugs for the treatment of NAFLD has not been evaluated. OBJECTIVE:This study aimed to investigate the expression levels of important regulators of hepatic lipid metabolism and the possible effect of the SST analog octreotide on these regulators. METHODS:SD rats were assigned to a control group and a high-fat diet group. Obese rats from the high-fat diet group were further divided into the obese and octreotide-treated groups. The body weight, plasma SST, fasting plasma glucose (FPG), insulin, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acid (FFA) levels were measured. Hepatic steatosis was evaluated based on the liver TG content, HE staining and oil red O staining. The SREBP-1c, ACC1, FAS, MTP, apoB and ADRP expression levels in the liver were also determined by RT-PCR, qRT-PCR, western blot or ELISA. RESULTS:The obese rats induced by high-fat diet expressed more SREBP-1c, FAS and ADRP but less MTP protein in the liver than those of control rats, whereas octreotide intervention reversed these changes and increased the level of apoB protein. Compared to the control group, obese rats showed increased liver ACC1, SREBP-1c and apoB mRNA levels, whereas octreotide-treated rats showed decreased mRNA levels of apoB and SREBP-1c. This was accompanied by increased body weight, liver TG contents, FPG, TG, TC, LDL-C, FFA, insulin and derived homeostatic model assessment (HOMA) values. Octreotide intervention significantly decreased these parameters. Compared to the control group, the obese group showed a decreasing trend on plasma SST levels, which were significantly increased by the octreotide intervention. CONCLUSION:Octreotide can ameliorate hepatic steatosis in obese rats, possibly by decreasing hepatic lipogenesis and increasing TG export from hepatocytes.

Project description:The first step in a behavioral study is represented by the organization of a suitable ethogram, that is, a formal description of individual components of the behavior. Then, each component of such a behavioral repertoire can be quantified (e.g., how many times it occurs, its duration, percent distribution, latency, etc.). However, it is our contention that the possibility to describe the behavior of a living being by means of hundreds or even thousands of numbers concerning isolated components, disjointed from the comprehensive behavioral architecture, does not imply the possibility to use those numbers to reconstruct the meaning of behavior. Such a level of comprehension requires a qualitative approach based on the analysis of behavioral structure and its underlying dynamics. By means of synergic utilization of quantitative and qualitative data a more complete description of a given behavior becomes available. In present study we discuss results obtained from observations of feeding behavior in two groups of male Wistar rats: a control group, under standard diet, and a second group, under hyperglycidic one. Results have been presented both in terms of quantitative evaluations and in terms of structural/qualitative ones, the latter obtained by means of T-pattern detection and analysis. As to quantitative results, mean durations showed a significant reduction of Walking and Feeding and an increase of Hind-Paw Licking and Body Grooming; concerning mean occurrences, a significant increase of Front-Paw Licking, Hind-Paw Licking, and Body Grooming was present; percent distributions showed significant reductions for Walking and Feeding and a significant increase for all grooming activities. As to qualitative assessments, T-pattern analysis unveiled a clear-cut behavioral reorganization induced by the hyperglycidic diet. If on the one hand, 50 different T-patterns were detected in subjects under standard diet, on the other hand, 703 different T-patterns were discovered in animals under hyperglycidic treatment, with a highly significant increase of mean lengths and a significant reduction of mean occurrences of T-patterns. Synergic evaluation of results in terms of quantitative and qualitative aspects shows, in rats fed with hyperglycidic diet, an increased anxiety condition, likely dependent on food-related stimuli and suggestive of a pervasive craving-related behavior.

Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of metabolic syndrome and has attracted widespread attention due to its increased prevalence. Daily dietary management is an effective strategy for the prevention of NAFLD. Quinoa, a nutritious pseudocereal, is abundant in antioxidative bioactive phytochemicals. In the present study, the effects of different amounts of quinoa on the progression of NAFLD and the related molecular mechanism were investigated.MethodsMale SD rats were simultaneously administered a high fat diet (HF) and different amounts of quinoa (equivalent to 100 g/day and 300 g/day of human intake, respectively). After 12 weeks of the intervention, hepatic TG (triglyceride) and TC (total cholesterol) as well as serum antioxidative parameters were determined, and hematoxylin-eosin staining (H&E) staining was used to evaluate hepatic steatosis. Differential metabolites in serum and hepatic tissue were identified using UPLC-QTOF-MSE. The mRNA expression profile was investigated using RNA-Seq and further verified using real-time polymerase chain reaction (RT-PCR).ResultsLow amounts of quinoa (equivalent to 100 g/d of human intake) effectively controlled the weight of rats fed a high-fat diet. In addition, quinoa effectively inhibited the increase in hepatic TG and TC levels, mitigated pathological injury, promoted the increase in SOD and GSH-Px activities, and decreased MDA levels. Nontarget metabolic profile analysis showed that quinoa regulated lipid metabolites in the circulation system and liver such as LysoPC and PC. RNA-Seq and RT-PCR verification revealed that a high amount of quinoa more effectively upregulated genes related to lipid metabolism [Apoa (apolipoprotein)5, Apoa4, Apoc2] and downregulated genes related to the immune response [lrf (interferon regulatory factor)5, Tlr6 (Toll-like receptor), Tlr10, Tlr11, Tlr12].ConclusionQuinoa effectively prevented NAFLD by controlling body weight, mitigating oxidative stress, and regulating the lipid metabolic profile and the expression of genes related to lipid metabolism and the immune response.

Project description:Increased visceral adipose tissue (VAT) is associated with metabolic dysfunction, while subcutaneous adipose tissue (SAT) is considered protective. The mechanisms underlying these differences are not fully elucidated. This study aimed to investigate molecular differences in VAT and SAT of male Wistar rats fed a cafeteria diet (CD) or a standard rodent diet (STD) for three months. The expression of fatty acid metabolism genes was analysed by quantitative real-time PCR. Global and gene-specific DNA methylation was quantified using the Imprint® Methylated DNA Quantification Kit and pyrosequencing, respectively. Bodyweight, retroperitoneal fat mass, insulin resistance, leptin and triglyceride concentrations and adipocyte hypertrophy were higher in CD- compared to STD-fed rats. The expression of solute carrier family 27 member 3 (Slc27a3), a fatty acid transporter, was 9.6-fold higher in VAT and 6.3-fold lower in SAT of CD- versus STD-fed rats. Taqman probes confirmed increased Slc27a3 expression, while pyrosequencing showed Slc27a3 hypomethylation in VAT of CD- compared to STD-fed rats. The CD decreased global methylation in both VAT and SAT, although no depot differences were observed. Dysregulated fatty acid influx in VAT, in response to a CD, provides insight into the mechanisms underlying depot-differences in adipose tissue expansion during obesity and metabolic disease. Abbreviations: CD: cafeteria diet; E2F1: E2F Transcription Factor 1; EMSA: electrophoretic mobility shift assay; EGFR: epidermal growth factor receptor; GCF: GC-Rich Sequence DNA-Binding Factor; HOMA-IR: Homeostasis model for insulin resistance; NKX2-1: NK2 homeobox 1; PCR: Polymerase chain reaction; qRT-PCR: quantitative real-time PCR; RF: retroperitoneal fat; SAT: subcutaneous adipose tissue; Slc27a3: solute carrier family 27 member 3; STD: standard diet; TNFα: tumour necrosis factor alpha; TTS: transcriptional start site; T2D: Type 2 Diabetes; VAT: visceral adipose tissue; WT1 I: Wilms' tumour protein 1.

Dataset Information

Synergistic Effect of Feeding Time and Diet on Hepatic Steatosis and Gene Expression in Male Wistar Rats.

Publications

Synergistic Effect of Feeding Time and Diet on Hepatic Steatosis and Gene Expression in Male Wistar Rats.

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