Hepatocytes: A key role in liver inflammation

Gong, Jin; Tu, Wei; Liu, Jingmei; Tian, Dean

doi:10.3389/fimmu.2022.1083780

Cited by 42 publications

(26 citation statements)

References 105 publications

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“…42 Hepatocytes are the primary cellular constituents of the liver that plays crucial role in the metabolic processes of carbohydrate, lipid and proteins. 43 The kidney plays a significant role in the metabolism processes of carbohydrate, with approximate 40% of systemic glucose production occurring in the proximal tubule during periods of fasting and under stress conditions. In contrast, while the intestinal tract does contribute to the metabolic responses 44 and provides the heart with energy through oxidative metabolism, 45 there is currently no statistical evidence to support a significant involvement of fetal gut and heart in neonatal metabolism.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide association study of neonatal metabolites

He,

Liu,

et al. 2023

Preprint

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SummaryThe hereditary component significantly influences the concentration of metabolites in adults. Nevertheless, the precise influence of genetic factors on neonatal metabolites remains uncertain. To bridge this gap, we employed genotype imputation techniques on large-scale low-pass genome data obtained from non-invasive prenatal testing. Subsequently, we conducted association studies on a total of 75 metabolic components in neonates. The study identified a total 17 previous reported associations and 13 novel discovered associations between single nucleotide polymorphisms and metabolic components. These associations were initially found in the discovery cohort (8,744 participants) and subsequently confirmed in a replication cohort (19,041 participants). The average heritability of metabolic components was calculated to be 76.2%, with a range of 69-78.8%. The aforementioned findings offer valuable insights pertaining to the genetic architecture of neonatal metabolism.In BriefLarge-scale genomes of maternal non-invasive prenatal testing provide insights into the genetic contribution to neonatal metabolism.HighlightsGWAS of 27,785 low-pass genomes revealed 13 novel associations of neonatal metabolic components.Estimated an average of 76.2% heritability of neonatal metabolic components and showed the individual concentration can be accurately predicted from polygenic risk scores.A total of 17 established relationships have been observed, providing evidence that maternal genomes can be utilized in neonatal metabolite GWAS.

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Section: Discussionmentioning

confidence: 99%

A genome-wide association study of neonatal metabolites

He,

Liu,

et al. 2023

Preprint

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“…Our investigative endeavors have been profoundly directed toward three distinct categories of rhythmically orchestrated cell types, namely, hepatocytes, adipocytes, and intestinal epithelial cells, all of which assume pivotal roles in physiological processes. Hepatocytes, which constitute the majority of liver mass, are central to an array of biochemical and metabolic functions 118 . Adipocytes, along with their secretory products, are involved in numerous physiological processes and significantly influence metabolic health 119,120 .…”

Section: Circadian Regulation Of Non‐immune Cell Functionmentioning

confidence: 99%

“…Hepatocytes, which constitute the majority of liver mass, are central to an array of biochemical and metabolic functions. 118 Adipocytes, along with their secretory products, are involved in numerous physiological processes and significantly influence metabolic health. 119 , 120 Intestinal epithelial cells, essential for food digestion, nutrient absorption, and maintaining intestinal epithelial homeostasis, play a vital role in responding to diseases.…”

Section: Circadian Regulation Of Non‐immune Cell Functionmentioning

confidence: 99%

The role of circadian clock in regulating cell functions: implications for diseases

Lin,

He,

Cai

et al. 2024

MedComm

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The circadian clock system orchestrates daily behavioral and physiological rhythms, facilitating adaptation to environmental and internal oscillations. Disruptions in circadian rhythms have been linked to increased susceptibility to various diseases and can exacerbate existing conditions. This review delves into the intricate regulation of diurnal gene expression and cell function by circadian clocks across diverse tissues. . Specifically, we explore the rhythmicity of gene expressions, behaviors, and functions in both immune and non‐immune cells, elucidating the regulatory effects and mechanisms imposed by circadian clocks. A detailed discussion is centered on elucidating the complex functions of circadian clocks in regulating key cellular signaling pathways. We further review the circadian regulation in diverse diseases, with a focus on inflammatory diseases, cancers, and systemic diseases. By highlighting the intimate interplay between circadian clocks and diseases, especially through clock‐controlled cell function, this review contributes to the development of novel disease intervention strategies. This enhanced understanding holds significant promise for the design of targeted therapies that can exploit the circadian regulation mechanisms for improved treatment efficacy.

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“…During AIH pathogenesis, APC cells activate T lymphocytes by mispresenting liver autoantigens as foreign antigens to uncharacterized T lymphocytes (Longhi et al, 2021). As unconventional APC cells, the presence of MHC class II molecules on the surface of hepatocytes has resulted in an enhanced autoimmune response to AIH (Gong et al, 2022). In vitro studies have shown that low concentrations of butyrate, a gut microbial metabolite, inhibit the proliferation of CD4 + T and CD8 + T cells (Correâ-Oliveira et al, 2016).…”

Section: Disruption Of Immune Cell Homeostasismentioning

confidence: 99%

The significance of gut microbiota in the etiology of autoimmune hepatitis: a narrative review

Sun,

Zhu,

Zhu

et al. 2024

Front. Cell. Infect. Microbiol.

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Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver that is mediated by autoimmunity and has complex pathogenesis. Its prevalence has increased globally. Since the liver is the first organ to be exposed to harmful substances, such as gut-derived intestinal microbiota and its metabolites, gut health is closely related to liver health, and the “liver-gut axis” allows abnormalities in the gut microbiota to influence the development of liver-related diseases such as AIH. Changes in the composition of the intestinal microbiota and its resultant disruption of the intestinal barrier and microbial transport are involved in multiple ways in the disruption of immune homeostasis and inflammation, thereby influencing the development of AIH. In terms of the mechanisms involved in immune, the gut microbiota or its metabolites, which is decreased in secondary bile acids, short-chain fatty acids (SCFAs), and polyamines, and increased in lipopolysaccharide (LPS), branched-chain amino acids (BCAA), tryptophan metabolite, amino acid, and bile acid, can disrupt immune homeostasis by activating various immune cells and immune-related signaling pathways, resulting in aberrant activation of the immune system. Clarifying this mechanism has significant clinical implications for the treatment of AIH with drugs that target intestinal microbiota and related signaling pathways. Therefore, this narrative review summarizes the progress in exploring the involvement of gut microbiota in the pathogenesis of AIH, with the aim of helping to improve the precise targeting of therapeutic treatments against AIH for the benefit of clinical AIH treatment.

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Hepatocytes: A key role in liver inflammation

Cited by 42 publications

References 105 publications

A genome-wide association study of neonatal metabolites

A genome-wide association study of neonatal metabolites

The role of circadian clock in regulating cell functions: implications for diseases

The significance of gut microbiota in the etiology of autoimmune hepatitis: a narrative review

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