PINT MASLD Mouse Intervention HFD
Ontology highlight
ABSTRACT:
INSTRUMENT(S): 6540 Q-TOF LC/MS, Q Exactive Focus
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Kati Hanhineva
PROVIDER: MSV000099345 | MassIVE | Wed Oct 01 00:18:00 BST 2025
REPOSITORIES: MassIVE
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Project description:Although maternal obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), the pathogenesis remains unclear. We aimed to evaluate the effect and mechanisms of multigenerational maternal western diet (WD) on MASLD progression, and test drug candidates in a preclinical model. Female mice were fed WD from 8 weeks before breeding initiation with a normal chow (NC)-fed male, throughout pregnancy and lactation. Male offspring were weaned onto NC or WD and assessed at the age of 16 weeks. Maternal WD feeding aggravated body weight gain, insulin resistance, steatosis and inflammation. Fibrosis was only observed in offspring exposed to maternal WD. Mechanistically, the latter exhibited reduced OXPHOS activity. Maternal WD aggravates MASLD in male offspring, with mitochondrial dysfunction contributing to disease severity.
2025-06-18 | GSE291363 | GEO
Project description:Lean male mice were fed a high fat diet (HFD, lard 24% w/w) for 16 weeks. At 9 weeks, when all hallmarks of prediabetes were established, groups of mice were treated with drug (rosiglitazone, pioglitazone, T0901317, or salicylate) for another 7 weeks together with the high fat diet. An additional group was switched back to a chow diet (dietary lifestyle intervention) after the first 9 weeks of high fat diet. All groups were compared to a control group receiving HFD alone and to a reference group fed chow (baseline reference) for the entire experimental period (16 weeks).
2014-05-14 | GSE57659 | GEO
Project description:The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Considering the fact that MASLD patients accompanying type 2 diabetes mellitus (T2DM) have high risk of developing metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis, and HCC, we treated low-dose streptozotocin (STZ; 40 mg/kg) for 5 consecutive days and subsequently fed a high-fat diet (HFD) to male C57BL/6J mice at 7 weeks of age (STZ+HFD). STZ+HFD mice gradually developed fatty liver, MASH, hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. In particular, from 20 weeks of age, MASH was evident, and from 32 weeks of age, advanced fibrosis was developed. At 38 weeks, a proportion of STZ+HFD mice developed HCC, which was subsequently observed in all mice up to 68 weeks of age. Furthermore, the hepatic transcriptomic features of STZ+HFD mice closely reflected those of obese patients with T2DM, MASH and MASLD-related HCC. Notably, dietary changes and tirzepatide administration alleviated MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ+HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients with metabolic dysfunction was successfully established.
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Project description:To identify potential role of macrophage LPCAT3 in progression of hepatic steatosis in mice, we isolated Kupffer cells from mice deficient for LPCAT3 in macrophages and fed a high fat diet for 16 weeks
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Project description:Lean male mice were fed a high fat diet (HFD, lard 24% w/w) for 16 weeks. At 9 weeks, when all hallmarks of prediabetes were established, groups of mice were treated with drug (metformin, glibenclamide, sitagliptin, rosiglitazone, pioglitazone, fenofibrate, T0901317, atorvastatin, salicylate or rofecoxib) for another 7 weeks together with the high fat diet. An additional group was switched back to a chow diet (dietary lifestyle intervention) after the first 9 weeks of high fat diet. All groups were compared to a control group receiving HFD alone and to a reference group fed chow (baseline reference) for the entire experimental period (16 weeks).
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Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease, has emerged as the most common chronic liver disease globally, affecting more than one-third of the world’s population. Its rate has increased by 13%, rising from 25% to 38% over the past three decades. MASLD is characterized by excessive fat accumulation in hepatocytes and, if left untreated, progresses to its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), which poses a significant global health concern as one of the leading causes of cirrhosis, cirrhotic complications, and hepatocellular carcinoma. The molecular determinants of MASLD stratification are not clearly defined and require additional investigation. In this study, we used male and female CC042 mice, a Collaborative Cross mouse strain susceptible to the development of MASLD, to analyze the global transcriptomic profile in liver and to clarify the molecular mechanisms involved in the progression of the disease. Male and female CC042 mice were maintained on a high fat/high sucrose (HF/HS) diet for 20, 40, or 60 weeks, and hepatic gene expression profiles were determined by next-generation RNA sequencing. Chronic feeding of the HF/HS diet induced profound alterations in gene expression at all time points. The number of significantly differentially expressed genes (DEGs) in the livers of male mice was greater than female mice at 20 and 40 weeks and reached a maximum of 2764 genes at 40 weeks. In contrast, the number of DEGs in the livers of female mice steadily increased with the time on diet reaching a maximum of 2974 DEGs at 60 weeks after HF/HS diet initiation. The number of upregulated DEGs was higher than downregulated DEGs in both male and female mice at all time points. Functional analysis of DEGs showed that in both sexes, the most dysregulated liver toxicity-related pathways were associated with liver fibrosis, liver necrosis/cell death, inflammation, steatosis, liver damage, and liver proliferation/hyperplasia. In male mice, pathways associated with fibrosis, necrosis/cell death, inflammation, and steatosis remained constant from 20 to 40 weeks, and activation of liver hyperplasia pathway was constant from 40 and 60 weeks. In contrast, in female mice, dysregulation of genes associated with these pathways gradually increased from 20 to 60 weeks after HF/HS diet initiation. Importantly, we found that the expression of 701 and 871 genes significantly correlated with total NASH pathology scores (Pearson r > |0.8|) in the livers of male and female mice, respectively. These findings provide comprehensive insights into the dynamics of time- and sex-specific transcriptomic changes during NAFLD progression. This knowledge can be helpful for identifying promising targets for prevention and treatment, as well as for determining key potential biomarkers of NAFLD to NASH progression.
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Project description:This study sought to interrogate the effects of lipids and lipid metabolites on the hepatic proteome. Protein expression in high-fat diet (HFD) mouse livers vs. livers of normal chow fed (NC) mice were investigated using multiplexed quantitative LC-MS/MS (TMT labeling). This experiment contains additional replicates for normal chow and mice on high-fat diet for 16 weeks.
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Project description:Lean male mice were fed a high fat diet (HFD, lard 24% w/w) for 16 weeks. At 9 weeks, when all hallmarks of prediabetes were established, groups of mice were treated with drug (rosiglitazone, pioglitazone, T0901317, or salicylate) for another 7 weeks together with the high fat diet. An additional group was switched back to a chow diet (dietary lifestyle intervention) after the first 9 weeks of high fat diet. All groups were compared to a control group receiving HFD alone and to a reference group fed chow (baseline reference) for the entire experimental period (16 weeks). One group (n=9) remained on maintenance chow throughout the entire study period (16 weeks) and served as healthy, age-matched control. After the nine week run-in period, the HFD fed mice were matched into thirteen groups based on body weight. The first group (n=9) was sacrificed immediately after matching. The second group (n=15) was continued on HFD until the end of the experiment at t=16 weeks. The fourth group (n=9) was switched to regular chow (dietary lifestyle intervention). The other groups (each n=9) continued on HFD supplemented with drugs typically used in clinical practice. More specifically, following drugs were mixed into HFD ; rosiglitazone (0.010% w/w), pioglitazone (0.010% w/w), T0901317 (0.010% w/w) and salicylate (0.40% w/w).
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