Characterization and Comparison of the Divergent Metabolic Consequences of High-Sugar and High-Fat Diets in Male Wistar Rats

Abstract

Diet-induced obesity (DIO) in laboratory rodents can serve as a model with which to study the pathophysiology of obesity, but obesogenic diets (high-sugar and/or high-fat) are often poorly characterised and simplistically aimed at inducing metabolic derangements for the purpose of testing the therapeutic capacity of natural products and other bioactive compounds. Consequently, our understanding of the divergent metabolic responses to different obesogenic diet formulations is limited. The aim of the present study was to characterise and compare differences in the metabolic responses induced by low-fat, medium-fat/high-sugar and high-fat diets in rats through multivariate statistical modelling. Young male Wistar rats were randomly assigned to CON (laboratory chow, low-fat), OB1 (high-sugar, medium-fat) or OB2 (high-fat) dietary groups (n = 24 each) for 17 weeks, after which metabolic responses were characterised. Projection-based multivariate analyses (principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA)) were used to explore the associations between measures of body composition and metabolism. Furthermore, we conducted a systematic literature survey to examine reporting trends in rat dietary intervention studies, and to determine how the metabolic responses observed in the present study compared to other recently published studies. The OB1 and OB2 dietary regimens resulted in distinct metabolic profiles, with OB1 characterised by perturbations in insulin homeostasis and adipose tissue secretory function, while OB2 was characterised by altered lipid and liver metabolism. This work therefore confirms, by means of direct comparison, that differences in dietary composition have a profound impact on metabolic and pathophysiological outcomes in rodent models of DIO. However, through our literature survey we demonstrate that dietary composition is not reported in the majority of rat dietary intervention studies, suggesting that the impact of dietary composition is often not considered during study design or data interpretation. This hampers the usefulness of such studies to provide enhanced mechanistic insights into DIO, and also limits the translatability of such studies within the context of human obesity.

The effects of a green Rooibos (Aspalathus linearis) extract on metabolic parameters and adipose tissue biology in rats fed different obesogenic diets

“…A comprehensive analysis of the differences in the metabolic outcomes between the three dietary groups was published else-where. 32 Briefly, diets OB1 and OB2 did not induce dramatic weight gain in the rats, but visceral adiposity and serum triacylglycerol levels were significantly higher in the OB1 and OB2 dietary groups than in CON. Furthermore, fasting insulin levels, insulin resistance, serum adiponectin and leptin levels were higher in the OB1 dietary group than in the CON and OB2 groups, while serum total cholesterol, LDL-cholesterol, IL-18, ALT and AST were higher in the OB2 dietary group than in the CON and OB1 groups.…”

“…Furthermore, fasting insulin levels, insulin resistance, serum adiponectin and leptin levels were higher in the OB1 dietary group than in the CON and OB2 groups, while serum total cholesterol, LDL-cholesterol, IL-18, ALT and AST were higher in the OB2 dietary group than in the CON and OB1 groups. 32 The effect of GRT supplementation on body composition and metabolic outcomes within each dietary group are shown in Table 1. When analysed per diet group, GRT supplementation had no effect on final body weight, visceral adiposity, liver index, fasting insulin concentrations, insulin resistance, serum lipid profiles or serum concentrations of adiponectin, leptin, TNF-α and IL-18 (Table 1).…”

“…After 16 weeks of dietary intervention (6 weeks of GRT supplementation), rats were fasted for 16 hours overnight and at 09:00 in the morning, an oral glucose tolerance test (OGTT) was performed as described previously. 32 Blood glucose levels were measured via tail prick at 3, 5, 10, 15, 20, 25, 30, 45, 60, 90 and 120 min. After 17 weeks of dietary intervention (7 weeks of GRT supplementation), the rats were weighed and euthanized in the non-fasted state by intraperitoneal injection with an overdose (160 mg per kg body weight) of sodium pentobarbitone, and subsequent exsanguination.…”

“…The perirenal visceral ( pv) fat from one flank was dissected as described previously 8 and the weight was recorded to serve as a surrogate marker for total visceral fat. 32 The livers were also dissected and weighed, and the liver index was calculated as liver weight/body weight × 100.…”

Frontiers in metabolic physiology grand challenges

“…Comparison of high-sugar and high-fat diets fed to rats and metabolic consequences were evaluated. A high-sugar, medium fat diet impacted insulin homeostasis and adipose secretory function whereas a high-fat diet primarily altered lipid and liver metabolism ( Kotzé-Hörstmann et al, 2022 ). Neuronal mechanisms in fasted rats were the focus of another study.…”