Project description:Mice on a reference (RD) or western diet (WD) supplemented with olive oil or omega-3 fatty acids (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA])
Project description:Hepatic transcriptome of junctional adhesion molecule A knockout, F11r–/– mice fed a Western diet (WD) for eight weeks. A cohort of WD-fed mice were treated with IgG or α4β7 mAb for four weeks starting at week four following initiation of the WD.
Project description:The aim is to look the effect of dietary fibers (cellulose or inulin) on the hepatic transcriptome of mice fed either a western diet (WD) or a chow diet (CD). C57Bl/6J male mice aged 8 weeks were housed at thermoneutrality (TN, 30°C) and fed a WD or a CD during 17 weeks. CD and WD were supplemented with 9% of dietary fibre which was either pure cellulose (9%, thereafter named “cellulose diet”) or a mixture of cellulose (2.25%) and inulin (6.75%, thereafter named “inulin diet”).
Project description:Exposure to maternal western-style diet (mWD) is associated with early development of metabolic dysfunction-associated fatty liver disease (MAFLD) in offspring. Kupffer cells (KCs), the main resident macrophage population in the liver, are known to promote MAFLD progression, however, the effects of mWD on KC subtypes, ontogeny, and gene expression in offspring are not fully understood. In this manuscript, we used two different models of mWD exposure and challenge in adulthood to understand the impact of mWD on KC proportion, ontogeny, and gene expression in adult offspring. Our data indicate that in the absence of challenge in adulthood, mWD results in increased KC proportion in offspring, with limited changes in KC ontogeny or liver phenotype. In contrast, mWD mice challenged with WD in adulthood had increased expression of inflammatory (Nlrp3) and fibrosis (Tgfb1) related genes compared to chow (CH)-WD fed mice. Although KC proportion and ontogeny were similar when comparing CH-WD and WD-WD fed mice, we found that WD-WD mice had a greater reduction in KC proportion and TdT labelling than CH-WD fed mice when normalized to their respective maternal diet controls. Similar results were found when mice were weaned onto normal chow and re-challenged with WD later on in adulthood. Bulk RNA sequencing data indicate that KCs from mWD mice re-challenged with WD in adulthood had increased expression of inflammatory and antigen presenting genes compared to KCs isolated from WD fed mice lacking mWD exposure. These findings highlight the intergenerational repercussions of mWD on liver phenotype as well as KC proportion and ontogeny and provide novel insight into the mechanisms dictating MAFLD.
Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition associated with western diet and sedentary lifestyle. Larval zebrafish is widely used as disease model and drug testing platform for liver diseases. Here, it was aimed to generate MASLD model of zebrafish at an early developmental stage of 9 – 12 dpf, by feeding larvae with high fat high cholesterol egg yolk (BEY) or custom designed palmitate, cholesterol and fructose rich, low fiber western diet (WD) and different diets. Diet induced fat accumulation and histopathological changes in gut-liver axis were defined in a time dependent manner. Whole organism level transcriptomic changes were determined with a bulk sequencing approach, that enabled comparison across diets and time points in an affordable manner. Both diets induced an upregulation of lipid/cholesterol transport genetic signatures. Interestingly cholesterol biosynthesis was activated in BEY fed larvae, while it was suppressed in WD-fed larvae. WD diet suppressed lipid synthesis and oxidoreductase activity gene signatures, activated a large network of ribosome biogenesis and translation genes, and suppressed cell cycle in the organism. Cyp7a1 was induced upon egg yolk feeding while it was suppressed in the WD group. WD diet induced lipid droplet formation in the intestinal tissue, as well as structural changes. This study provides an elaborate investigation of western diet induced zebrafish MASLD model by reflecting structural alterations in the liver-gut axis and important gene expression. It features western diet as an effective inducer of early larval MASLD.
Project description:Macrophages are considered as a homogeneous population in the heart. We used single cell RNA sequencing (scRNA-seq) to analyze thediversity of macrophages in control diet (CD) mouse, high fat diet (HFD) mouse and Western diet (WD) mouse heart.
