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Impact of Free-Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety-Like Behavior in Rats.

ABSTRACT: OBJECTIVE:Rats were exposed to free-choice diets (fat plus one of two different sugar solutions, glucose or sucrose), and the metabolic consequences and impact on locomotor activity and anxiety-like behavior were explored. METHODS:For 3 weeks, 7-week-old male rats were offered either chow only or free-choice high-fat diets differing in their added sugar: no sugar, sucrose, or glucose. In a second experiment, after 2 weeks on the diets, rats were switched from high sucrose to high glucose for two additional weeks. Metabolic end points included body weight, food intake, food choice, glycemic control, metabolic hormones, fat pad weight, brown adipose tissue weight, and gene expression. Behavioral analysis included locomotor and anxiety-like activity in the open field and elevated plus maze. RESULTS:Both sugar diets enhanced adiposity and induced hyperphagia, favoring unhealthier dietary selection above that of the control diets (chow or free-choice high-fat with no sugar). Despite isocaloric intake in the sugar-containing diets, offering glucose instead of sucrose was associated with improved insulin sensitivity. The sugar-containing diets reduced activity (but with movements of increased velocity) and induced an anxiety-like phenotype. CONCLUSIONS:Although free-choice diets negatively impacted on metabolism and anxiety-like behavior, replacing sucrose with glucose improved insulin sensitivity and may therefore be better for health.

SUBMITTER: Peris-Sampedro F

PROVIDER: S-EPMC6590171 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Impact of Free-Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety-Like Behavior in Rats.

Peris-Sampedro Fiona F Mounib Myriam M Schéle Erik E Edvardsson Christian E CE Stoltenborg Iris I Adan Roger A H RAH Dickson Suzanne L SL

Obesity (Silver Spring, Md.) 20190130 3

<h4>Objective</h4>Rats were exposed to free-choice diets (fat plus one of two different sugar solutions, glucose or sucrose), and the metabolic consequences and impact on locomotor activity and anxiety-like behavior were explored.<h4>Methods</h4>For 3 weeks, 7-week-old male rats were offered either chow only or free-choice high-fat diets differing in their added sugar: no sugar, sucrose, or glucose. In a second experiment, after 2 weeks on the diets, rats were switched from high sucrose to high ...[more]

PMID: 30699240

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Project description:Background and purposeThe link between type 2 diabetes mellitus (T2DM) and depression is bidirectional. However, the possibility that metabolic disorders may elicit anxiogenic-like/depressive-like symptoms or alter the efficacy of antidepressant drugs remains poorly documented. This study explored the influence of T2DM on emotionality and proposed a therapeutic strategy that might be used in depressed diabetic patients.Experimental approachMice were fed a high-fat diet (HFD) and subjected to a full comprehensive metabolic and behavioural analysis to establish correlations between metabolic and psychiatric disorders. In vivo intra-hippocampal microdialysis was also applied to propose a mechanism underpinning the phenotype of mice fed the HFD. Finally, we tested whether chronic administration of the selective 5-HT reuptake inhibitor escitalopram or HFD withdrawal could reverse HFD-induced metabolic and behavioural anomalies.Key resultsThe increased body weight, hyperglycaemia and impaired glucose tolerance in response to HFD were correlated with anxiogenic-like/depressive-like symptoms. Moreover, this phenotype was associated with decreased extracellular 5-HT levels in the hippocampus which may result from increased sensitivity of the dorsal raphe 5-HT1A autoreceptor. Interestingly, the beneficial effect of prolonged administration of escitalopram was abolished in HFD-fed mice. On the contrary, HFD withdrawal completely reversed metabolic impairments and positively changed symptoms of anxiety, although some behavioural anomalies persisted.Conclusions and implicationsOur data provide clear-cut evidence that both pathologies are finely correlated and associated with impaired 5-HT mediated neurotransmission in the hippocampus. Further experiments are warranted to define the most adequate strategy for the treatment of such co-morbidity.Linked articlesThis article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.

Project description: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.

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Impact of Free-Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety-Like Behavior in Rats.

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Impact of Free-Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety-Like Behavior in Rats.

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