When the liver is in poor condition, so is the heart - cardiac remodelling in MASH mouse models.

Metabolic dysfunction-associated steatohepatitis (MASH) confers a risk for cardiovascular diseases in patients. Animal models may help exploring the mechanisms linking liver and heart diseases. Hence, we explored the cardiac phenotype in two MASH mouse models: foz/foz mice fed a high-fat diet (HFD) for 24 or 60 weeks and C57BL/6J mice fed a high-fat-, high-cholesterol-, and high-fructose diet for 60 weeks. Angiotensin II (AngII) was used as an additional cardiovascular stressor for 4 weeks in 10 weeks HFD-fed foz/foz mice. Foz/foz mice with fibrosing MASH developed cardiac hypertrophy with adverse cardiac remodelling not seen in WT similarly fed the HFD. AngII caused hypertension and up-regulated the expression of genes contributing to pathological cardiac hypertrophy (Nppa, Myh7) more severely so in foz/foz mice than in controls. After 60 weeks of HFD, while liver disease had progressed to burn-out non steatotic MASH with hepatocellular carcinoma in 50% of the animals, the cardiomyopathy did not. In an independent model (C57BL/6J mice fed a fat-, cholesterol- and fructose-rich diet), moderate fibrosing MASH is associated with cardiac fibrosis and dysregulation of genes involved in pathological remodelling (Col1a1, Col3a1, Vim, Myh6, Slc2a1). Thus, animals with MASH present consistent adverse structural changes in the heart with no patent alteration of cardiac function even when stressed with exogenous AngII. Liver disease, and likely not overfeeding or aging alone, is associated with this cardiac phenotype. Our findings support foz/foz mice as suitable for studying links between MASH and heart structural changes ahead of heart failure.

Bott S ，Lallement J ，Marino A ，Daskalopoulos EP ，Beauloye C ，Esfahani H ，Dessy C ，Leclercq IA ... -  《-》

Protective Effects of Hepatocyte Stress Defenders, Nrf1 and Nrf2, against MASLD Progression.

Akl MG ，Li L ，Widenmaier SB 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Dynamic changes of gut microbiota in mouse models of metabolic dysfunction-associated steatohepatitis and its transition to hepatocellular carcinoma.

Dysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction-associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH-associated hepatocellular carcinoma (MASH-HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA-16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH-HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH-fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.

Wang YL ，Liu C ，Yang YY ，Zhang L ，Guo X ，Niu C ，Zhang NP ，Ding J ，Wu J ... -  《-》

Choline-deficient, high-fat diet-induced MASH in Göttingen Minipigs: characterization and effects of a chow reversal period.

Hvid H ，Hjuler ST ，Bedossa P ，Tiniakos DG ，Kamzolas I ，Harder LM ，Xue Y ，Perfield JW ，Kirk RK ，Latta M ，Mikkelsen LF ，Pedersen HD ，LITMUS Investigators ... -  《-》

Endoplasmic reticulum stress does not contribute to steatohepatitis in obese and insulin-resistant high-fat-diet-fed foz/foz mice.

Legry V ，Van Rooyen DM ，Lambert B ，Sempoux C ，Poekes L ，Español-Suñer R ，Molendi-Coste O ，Horsmans Y ，Farrell GC ，Leclercq IA ... -  《-》