Sex hormones differently regulate lipid metabolism genes in primary human hepatocytes.

Background: Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher in men than in women. Hormonal and genetic causes may account for the sex differences in MASLD. Current human in vitro liver models do not sufficiently take the influence of biological sex and sex hormones into consideration.

Cell atlas of the regenerating human liver after portal vein embolization.

The liver has the remarkable capacity to regenerate. In the clinic, regeneration is induced by portal vein embolization, which redirects portal blood flow, resulting in liver hypertrophy in locations with increased blood supply, and atrophy of embolized segments. Here, we apply single-cell and single-nucleus transcriptomics on healthy, hypertrophied, and atrophied patient-derived liver samples to explore cell states in the regenerating liver.

Positive allosteric GABA receptor modulation counteracts lipotoxicity-induced gene expression changes in hepatocytes .

We have previously shown that the novel positive allosteric modulator of the GABA receptor, HK4, exerts hepatoprotective effects against lipotoxicity-induced apoptosis, DNA damage, inflammation and ER stress This might be mediated by downregulated phosphorylation of the transcription factors NF-κB and STAT3. The current study aimed to investigate the effect of HK4 on lipotoxicity-induced hepatocyte injury at the transcriptional level. HepG2 cells were treated with palmitate (200 μM) in the presence or absence of HK4 (10 μM) for 7 h.

Selective ablation of P53 in pancreatic beta cells fails to ameliorate glucose metabolism in genetic, dietary and pharmacological models of diabetes mellitus.

Objective: Beta cell dysfunction and death are critical steps in the development of both type 1 and type 2 diabetes (T1D and T2D), but the underlying mechanisms are incompletely understood. Activation of the essential tumor suppressor and transcription factor P53 (also known as TP53 and Trp53 in mice) was linked to beta cell death in vitro and has been reported in several diabetes mouse models and beta cells of humans with T2D. In this article, we set out to determine the beta cell specific role of P53 in beta cell dysfunction, cell death and development of diabetes in vivo.

Positive allosteric γ-aminobutyric acid type A receptor modulation prevents lipotoxicity-induced injury in hepatocytes in vitro.

Aim: To determine if a novel positive allosteric modulator of the γ-aminobutyric acid type A (GABA ) receptor, the thioacrylamide-derivative HK4, which does not penetrate the blood-brain barrier, protects human hepatocytes against lipotoxicity-induced injury.

Materials And Methods: Allosteric modulation of the GABA receptor by HK4 was determined by patch clamp in HEK-293 cells, calcium influx in INS-1E cells and by using the specific GABA channel blockers picrotoxin and tert-butylbicyclophosphorothionate (TBPS) in HepG2 cells. Apoptosis was analysed using caspase 3/7, terminal deoxynucleotidyl transferase-dUTP nick end labelling (TUNEL) and array assays in HepG2 cells and/or human primary hepatocytes.