Hepatocytes of Wistar and Sprague Dawley rats differ significantly in their central metabolism

Abstract

Wistar and Sprague-Dawley (SD) rats are most commonly used experimental rats. They have similar genetic background and are therefore, not discriminated in practical research. In this study, we compared metabolic profiles of Wistar and SD rat hepatocytes from middle (6 months) and old (23 months) age groups.Principle component analysis (PCA) on the specific uptake and production rates of amino acids, glucose, lactate and urea indicated clear differences between Wistar and SD rat hepatocytes. SD rat hepatocytes showed higher uptake rates of various essential and non-essential amino acids, particularly in early culture phases (0-12 h) compared to later phases (12-24 h). SD hepatocytes seem to be more sensitive to isolation procedure and in vitro culture requiring more amino acids for cellular maintenance and repair. Major differences between Wistar and SD rat hepatocytes were observed for glucose and branched chain amino acid metabolism. We conclude that the observed differences in the central carbon metabolism of isolated hepatocytes from these two rats should be considered when using one or the other rat type in studies on metabolic effects or diseases such as diabetes or obesity. K E Y W O R D Saging, amino acid metabolism, glucose metabolism, metabolic profiles, rat hepatocytes, RRID:Rats are frequently used laboratory animals for research owing to their easy maintenance, short gestation period and life span. Wistar and Sprague-Dawley (SD) are the two most common outbred rats in the laboratory and are often used in toxicological and aging studies. 1 Wistar rats are commonly used in Europe and SD rats are generally preferred in the US. 2 Wistar and SD rats have been used to study metabolic diseases like insulin resistance in type 2 diabetes and high fat diet induced obesity. [3][4][5][6] Differences between Wistar and SD rats regarding food intake, growth rate, hormone levels, 7 as well as tumor genesis 8 are known. Recently, a GC-MS based urinary metabolomics study revealed differences between the two rats under fasting and fed conditions and upon exposure to ethanol. 9 Another study, using nuclear magnetic resonance (NMR) based metabonomics showed differences in metabolite profiles in urine samples of these two types of rats. 10 Variations in the expression of CYP 450 1A and 3A enzymes have been described. 11 Differences between these two rats have also been observed in the manifestation of neurotoxicity 2 and drug toxicity. 12,13,14 Since these two rat strains are also commonly used in in vitro studies, a detailed study on the metabolic profiles of isolated hepatocytes in culture from these two rat strains would be very helpful.

High-fructose diet initiated during adolescence does not affect basolateral amygdala excitability or affective-like behavior in Sprague Dawley rats

“…Higher baseline corticosterone levels have also been reported in Wistar rats compared to Sprague Dawley [48], possibly affecting both fructose-induced hepatic gluconeogenesis [49] and affective behavior via HPA axis activation [24,50]. Cultured hepatocytes from Sprague Dawley rats also exhibit faster glucose and amino acid metabolism than in Wistar rats [51], suggesting Sprague Dawley and Wistar rats may metabolize fructose in the liver at different rates.…”

Microanatomical Record of Cortical Bone Remodeling and High Vascularity in a Fossil Giant Rat Midshaft Femur

“…The giant femur measured 6.15 mm in M-L and 4.87 mm in C-C midshaft diameter, whereas the smaller rat's femur midshaft was 2.33 and 1.98 mm wide in the M-L and C-C aspects, respectively. By extension, the giant femoral size is likely to have been associated with a larger body mass and skeletal frame (Damuth et al, 1990), well above a typical 150-300 g weight reported for common rats (e.g., Bromage et al, 2009;Felder et al, 2017;Garg et al, 2018). At the histological level, both samples exhibited circumferential bone periosteally and endosteally, and multiple osteocyte lacunae scattered throughout the entirety of bone (Figs.…”

Atypical antipsychotics olanzapine and clozapine increase bone loss in female rats with experimental periodontitis

“…One of the possible mechanisms related to increased blood lipids is the olanzapine‐enhanced expression of steroid regulatory element‐binding protein (SREBP)‐1c expression, for which transcription in adipose tissue and liver depends on insulin 39 . Despite hepatic‐related metabolic abnormalities models being reproducible in Wistar and Sprague Dawley lineages, 43,44 antipsychotic changes in carbohydrates and lipids metabolism should be carefully interpreted due to differences in hepatic amino acid uptake and glycolytic cycle among species and even in rat strains 45 . Thus, the use of the Wistar strain limits comparisons with other data in the literature, constituting a limitation of this work, but it brings important information about the metabolic effects of olanzapine and clozapine.…”