Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice

Park, Seokjae; Oh, Sungjoon; Kim, Eun-Kyoung

doi:10.1016/j.jbc.2022.102682

Cited by 7 publications

(3 citation statements)

References 71 publications

(89 reference statements)

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“…An analogous decrease in plasma valine and leucine was also observed in our recent WKY rat model when the animals were fed a high fat (HF) diet [47]. Park et al detected a decrease in circulating BCAAs in C57BL/6N mice fed an HF diet [50]. These findings contrast with most previous publications reporting elevated BCAA levels as a significant marker of obesity and diabetes [51].…”

Section: Discussionsupporting

confidence: 59%

Metabolomic Study of Aging in fa/fa Rats: Multiplatform Urine and Serum Analysis

et al. 2023

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Zucker fatty (fa/fa) rats represent a well-established and widely used model of genetic obesity. Because previous metabolomic studies have only been published for young fa/fa rats up to 20 weeks of age, which can be considered early maturity in male fa/fa rats, the aim of our work was to extend the metabolomic characterization to significantly older animals. Therefore, the urinary profiles of obese fa/fa rats and their lean controls were monitored using untargeted NMR metabolomics between 12 and 40 weeks of age. At the end of the experiment, the rats were also characterized by NMR and LC-MS serum analysis, which was supplemented by a targeted LC-MS analysis of serum bile acids and neurotransmitters. The urine analysis showed that most of the characteristic differences detected in young obese fa/fa rats persisted throughout the experiment, primarily through a decrease in microbial co-metabolite levels, the upregulation of the citrate cycle, and changes in nicotinamide metabolism compared with the age-related controls. The serum of 40-week-old obese rats showed a reduction in several bile acid conjugates and an increase in serotonin. Our study demonstrated that the fa/fa model of genetic obesity is stable up to 40 weeks of age and is therefore suitable for long-term experiments.

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Section: Discussionsupporting

confidence: 59%

Metabolomic Study of Aging in fa/fa Rats: Multiplatform Urine and Serum Analysis

et al. 2023

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“… 29 Treatment of mice with GLP-1R agonists such as liraglutide (Lira) dose dependently suppress appetite and body mass and can, at higher doses, reduce body mass by greater than 25% over just 14 days of treatment after 8 weeks of a high-fat diet. 30 Human clinical trials with Lira in people with NASH elicit 5%–10% weight loss. 10 Therefore, to enhance the potential translatability of Lira treatment in mice to humans with NASH, we utilized a submaximal dose of Lira with the aim to elicit similar reductions in body mass/adiposity to that observed in participants within clinical trials.…”

Section: Resultsmentioning

confidence: 99%

Combination of an ACLY inhibitor with a GLP-1R agonist exerts additive benefits on nonalcoholic steatohepatitis and hepatic fibrosis in mice

Desjardins,

Wu,

Lavoie

et al. 2023

Cell Reports Medicine

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“…Liquid chromatography–tandem mass spectrometry (LC‐MS/MS) has been applied to identify metabolites in patients with depression and characterize the link between differential metabolites and cognitive neurological dysfunction (Duan et al., 2022 ). Although there has been evidence that GLP‐1 analogs such as liraglutide elicit metabolomic changes, such as changes in the levels of fatty acids and amino acids in the hypothalamus (Park et al., 2022 ), the metabolomic alterations evoked by dulaglutide in the hippocampus are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Dulaglutide treatment reverses depression‐like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress

Jin,

Zhang,

Huang

et al. 2024

Brain and Behavior

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IntroductionTreatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long‐acting GLP‐1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice.MethodsSixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety‐ and depression‐like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography–tandem mass spectrometry‐based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment.ResultsThree weeks of dulaglutide treatment significantly reversed depressive‐like but not anxiety‐like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy.ConclusionThe antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant‐like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression.

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Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice

Cited by 7 publications

References 71 publications

Metabolomic Study of Aging in fa/fa Rats: Multiplatform Urine and Serum Analysis

Metabolomic Study of Aging in fa/fa Rats: Multiplatform Urine and Serum Analysis

Combination of an ACLY inhibitor with a GLP-1R agonist exerts additive benefits on nonalcoholic steatohepatitis and hepatic fibrosis in mice

Dulaglutide treatment reverses depression‐like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress

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