Numerous nuclear receptors including farnesoid X receptor, liver X receptor, peroxisome proliferator-activated receptors, pregnane X receptor, hepatic nuclear factors have been extensively studied within the context of non-alcoholic fatty liver disease (NAFLD). Following the first description of the Aryl hydrocarbon Receptor (AhR) in the 1970s and decades of research which unveiled its role in toxicity and pathophysiological processes, the functional significance of AhR in NAFLD has not been completely decoded. Recently, multiple research groups have utilized a plethora of in vitro and in vivo models that mimic NAFLD pathology to investigate the functional significance of AhR in fatty liver disease. This review provides a comprehensive account of studies describing both the beneficial and possible detrimental role of AhR in NAFLD. A plausible reconciliation for the paradox indicating AhR as a ‘double-edged sword’ in NAFLD is discussed. Finally, understanding AhR ligands and their signaling in NAFLD will facilitate us to probe AhR as a potential drug target to design innovative therapeutics against NAFLD in the near future.

Breeding efforts in cereal crops directed toward developing or improving end-use products of grain require assessment of existing phenotypic variance and an understanding of the genetic control of grain quality traits. To this end, a grain sorghum [Sorghum bicolor (L.) Moench] mapping population consisting of 113 F_2:7 recombinant inbred lines (RILs) derived from a cross between Sureño and RTx430 was evaluated in multiple environments for grain composition (fat, fiber, protein, starch) using near-infrared reflectance spectroscopy (NIRS), and size estimates of grain parts (embryo, vitreous endosperm, floury endosperm, kernel area) using an image-based phenotyping software system. Estimates of broad-sense heritability of grain compositional traits ranged from 0.11 to 0.90, whereas those of grain size ranged from 0.16 to 0.72. Composite interval mapping (CIM) was applied to a single nucleotide polymorphism (SNP)-based linkage map to identify marker-trait associations, and through these efforts, a total of 37 quantitative trait loci (QTL) for grain quality were identified across environments. Each QTL explained between 7 and 23% of the phenotypic variation for a given grain trait. Three of the five QTL that colocalized were for traits with significant negative correlation, which included grain protein content that was negatively correlated with grain starch content. In addition, several traits that were positively correlated (e.g. fat and fiber content) also revealed colocalized QTL. Finally, we compared the present study with previous studies identifying grain composition trait loci in an effort to identify genomic regions controlling grain traits across a diversity of environments and sorghum genotypes.

Disruptions in early-life gut microbiota and metabolites associated with maternal Western-style diet (WD) during critical windows of development are linked to metabolic and inflammatory diseases in offspring, including metabolic dysfunction-associated steatotic liver disease (MASLD) in later life. These disturbances can alter microbial metabolite production, such as tryptophan derivatives, which are crucial for immune and metabolic regulation. However, the specific effects of maternal supplementation with tryptophan metabolites on offspring gut microbiome maturation and MASLD risk remain unexplored. WD-fed mouse dams were supplemented with microbial metabolites indole (Ind) or indole-3-acetic acid (I3A) during gestation and lactation; male offspring were weaned to chow diet for 9 weeks, followed by a 4-week WD challenge. Fecal microbiota transfer (FMT) was performed from offspring to naïve recipients, followed by a 4-week WD challenge. Human LX-2 stellate cells were used to study mechanisms for indole and very long-chain (VLC) ceramide effects on TGF-β-induced fibrosis. Maternal supplementation with Ind or I3A had long-term protective effects in adult WD-challenged offspring against excess weight gain, steatosis, stellate cell activation, and fibrosis. Perinatal exposure to Ind or I3A activated offspring aryl hydrocarbon receptor (AHR) signalling in gut and liver, which trans-repressed known and new target genes, including ceramidases Asah2 and Acer3, leading to increased VLC ceramides. FMT from offspring with perinatal exposure to Ind protected recipients from WD-induced fibrogenesis and increased beneficial VLC ceramides in recipient livers. In vitro, LX-2 stellate cells cultured with Ind or VLC ceramides demonstrated an anti-fibrotic effect, which was abolished by AHR inhibition. Maternal indole supplementation, through sustained activation of AHR in offspring gut and liver and an increase in hepatic VLC ceramides, prevents diet-induced MASLD and fibrosis in offspring, offering a novel therapeutic pathway for prevention of paediatric MASLD. See Acknowledgements.