Dataset Information

Multi-layered metabolic effects of trehalose on the liver proteome in apoE-knockout mice model of liver steatosis.

ABSTRACT:

Background

Metabolic dysfunction-associated fatty liver disease has been well documented as a key independent risk factor for the development of atherosclerosis. A growing body of evidence suggests that due to its numerous favorable molecular effects, trehalose may exert beneficial effects in counteracting liver steatosis. In our previous study, we described the antiatherosclerotic and antisteatotic properties of trehalose, which we attributed to the induction of autophagy. Considering the pleiotropic activities of trehalose, our present study aimed to extend our preliminary results with the comprehensive examination of proteome-wide changes in the livers of high-fat-fed apoE-/- mice.

Methods

Thus, we applied modern, next-generation proteomic methodology to comprehensively analyze the effects of trehalose on the alterations of liver proteins in apoE-/- mice.

Results

Our proteomic analysis showed that the administration of trehalose elicited profound changes in the liver proteome of apoE-/- mice. The collected data allowed the identification and quantitation of 3 681 protein groups of which 129 were significantly regulated in the livers of trehalose-treated apoE-/- mice.

Conclusions

The presented results are the first to highlight the effects of disaccharide on the induction of proteins mainly related to the metabolism and elimination of lipids, especially by peroxisomal β-oxidation. Our study provides evidence for the pleiotropic activity of trehalose, extending our initial observations of its potential mechanisms responsible for mitigating of liver steatosis, which paves the way for new pharmacological strategies in fatty liver disease.

SUBMITTER: Pogoda W

PROVIDER: S-EPMC11294376 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multi-layered metabolic effects of trehalose on the liver proteome in apoE-knockout mice model of liver steatosis.

Pogoda Weronika W Koczur Jakub J Stachowicz Aneta A Madej Józef J Olszanecki Rafał R Suski Maciej M

Pharmacological reports : PR 20240624 4

<h4>Background</h4>Metabolic dysfunction-associated fatty liver disease has been well documented as a key independent risk factor for the development of atherosclerosis. A growing body of evidence suggests that due to its numerous favorable molecular effects, trehalose may exert beneficial effects in counteracting liver steatosis. In our previous study, we described the antiatherosclerotic and antisteatotic properties of trehalose, which we attributed to the induction of autophagy. Considering t ...[more]

PMID: 38913153

Similar Datasets

Project description:Background: In patients with metabolic-associated fatty liver disease (MAFLD), hepatic steatosis is the first step of diagnosis, and it is a risk predictor that independently predicts insulin resistance, cardiovascular risk, and mortality. Urine biomarkers have the advantage of being less complex, with a lower dynamic range and fewer technical challenges, in comparison to blood biomarkers. Methods: Hepatic steatosis was measured by magnetic resonance imaging (MRI), which measured the proton density fat fraction (MRI-PDFF). Mild hepatic steatosis was defined as MRI-PDFF 5−10% and severe hepatic steatosis was defined as MRI-PDFF > 10%. Results: MAFLD patients with any kidney diseases were excluded. There were 53 proteins identified by mass spectrometry with significantly different expressions among the healthy control, mild steatosis, and severe steatosis patients. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of these significantly changed urinary molecular features correlated with the liver, resulting in the dysregulation of carbohydrate derivative/catabolic/glycosaminoglycan/metabolic processes, insulin-like growth factor receptor levels, inflammatory responses, the PI3K−Akt signaling pathway, and cholesterol metabolism. Urine alpha-1-acid glycoprotein 1 (ORM1) and ceruloplasmin showed the most significant correlation with the clinical parameters of MAFLD status, including liver fat content, fibrosis, ALT, triglycerides, glucose, HOMA-IR, and C-reactive protein. According to ELISA and western blot (30 urine samples, normalized to urine creatinine), ceruloplasmin (ROC 0.78, p = 0.034) and ORM1 (ROC 0.87, p = 0.005) showed moderate diagnostic accuracy in distinguishing mild steatosis from healthy controls. Ceruloplasmin (ROC 0.79, p = 0.028) and ORM1 (ROC 0.81, p = 0.019) also showed moderate diagnostic accuracy in distinguishing severe steatosis from mild steatosis. Conclusions: Ceruloplasmin and ORM1 are potential biomarkers in distinguishing mild and severe steatosis in MAFLD patients.

Project description:ObjectivePARKIN is an E3 ubiquitin ligase that regulates mitochondrial quality control through a process called mitophagy. Recent human and rodent studies suggest that loss of hepatic mitophagy may occur during the pathogenesis of obesity-associated fatty liver and contribute to changes in mitochondrial metabolism associated with this disease. Whole-body Prkn knockout mice are paradoxically protected against diet-induced hepatic steatosis; however, liver-specific effects of Prkn deficiency cannot be discerned in this model due to pleotropic effects of germline Prkn deletion on energy balance and subsequent protection against diet-induced obesity. We therefore generated the first liver-specific Prkn knockout mouse strain (LKO) to directly address the role of hepatic Prkn.MethodsLittermate control (WT) and LKO mice were fed regular chow (RC) or high-fat diet (HFD) and changes in body weight and composition were measured over time. Liver mitochondrial content was assessed using multiple, complementary techniques, and mitochondrial respiratory capacity was assessed using Oroboros O2K platform. Liver fat was measured biochemically and assessed histologically, while global changes in hepatic gene expression were measured by RNA-seq. Whole-body and tissue-specific insulin resistance were assessed by hyperinsulinemic-euglycemic clamp with isotopic tracers.ResultsLiver-specific deletion of Prkn had no effect on body weight or adiposity during RC or HFD feeding; however, hepatic steatosis was increased by 45% in HFD-fed LKO compared with WT mice (P < 0.05). While there were no differences in mitochondrial content between genotypes on either diet, mitochondrial respiratory capacity and efficiency in the liver were significantly reduced in LKO mice. Gene enrichment analyses from liver RNA-seq results suggested significant changes in pathways related to lipid metabolism and fibrosis in HFD-fed Prkn knockout mice. Finally, whole-body insulin sensitivity was reduced by 35% in HFD-fed LKO mice (P < 0.05), which was primarily due to increased hepatic insulin resistance (60% of whole-body effect; P = 0.11).ConclusionsThese data demonstrate that PARKIN contributes to mitochondrial homeostasis in the liver and plays a protective role against the pathogenesis of hepatic steatosis and insulin resistance.

Dataset Information

Multi-layered metabolic effects of trehalose on the liver proteome in apoE-knockout mice model of liver steatosis.

Background

Methods

Results

Conclusions

Publications

Multi-layered metabolic effects of trehalose on the liver proteome in apoE-knockout mice model of liver steatosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets