Nuclear HMGB1 protects from nonalcoholic fatty liver disease through negative regulation of liver X receptor

Personnaz, Jean; Piccolo, Enzo; Dortignac, Alizée; Iacovoni, Jason S.; Mariette, Jérôme; Rocher, Vincent; Polizzi, Arnaud; Batut, Aurélie; Deleruyelle, Simon; Bourdens, L.; Delos, Océane; Combes‐Soia, Lucie; Paccoud, Romain; Moreau, E.; Martins, Frédéric; Clouaire, Thomas; Benhamed, Fadila; Montagner, Alexandra; Wahli, Walter; Schwabe, Robert F.; Yart, Armelle; Castan-Laurell, Isabelle; Bertrand‐Michel, Justine; Burlet‐Schiltz, Odile; Postic, Catherine; Denechaud, Pierre-Damien; Moro, Cédric; Legube, Gaëlle; Lee, Chih-Hao; Guillou, Hervé; Valet, Philippe; Dray, Cédric; Pradère, Jean-Philippe

doi:10.1126/sciadv.abg9055

Cited by 7 publications

(3 citation statements)

References 69 publications

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“…In the therapeutic context, silencing HMGB1 may result in losing its critical nuclear housekeeping function in host cells. Personnaz et al 39 reported that liver-specific HMGB1-deficient mice exhibited exacerbated hepatic steatosis. An alternative approach is to improve the intracellular distribution of HMGB1 by increasing SIRT1 expression or activity to retain HMGB1 in the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Aging aggravates liver fibrosis through downregulated hepatocyte SIRT1-induced liver sinusoidal endothelial cell dysfunction

Dai,

Qing,

Jiang

et al. 2023

Hepatology Communications

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Background: Aging increases the susceptibility to chronic liver diseases and hastens liver fibrosis deterioration, but the underlying mechanisms remain partially understood. The aim of this study was to investigate the effect of aging and chronic liver diseases on hepatocyte Sirtuin 1 (SIRT1) and LSECs and their contribution to liver fibrosis pathogeneses. Methods: Young (8–12 wk) and aged (18–20 mo) mice were subjected to carbon tetrachloride–induced liver fibrosis. Primary HSCs and LSECs were isolated and cocultured for in vitro experiments. Liver tissues and blood samples from healthy controls and patients with liver fibrosis were analyzed. Results: Downregulated hepatocytes SIRT1 in aged mice increased high mobility group box 1 acetylation, cytoplasmic translocation, and extracellular secretion, causing LSECs dysfunction by means of the toll-like receptor 4/AK strain transforming (AKT)/endothelial nitric oxide synthase pathway, ultimately activating HSCs and increasing susceptibility to liver injury and fibrosis. Adeno-associated virus-mediated overexpression of SIRT1 in hepatocytes suppressed the abovementioned alterations and attenuated carbon tetrachloride–induced liver injury and fibrosis in liver fibrosis mice, and there were no significant differences in liver injury and fibrosis indicators between young and aged mice after SIRT1 overexpression treatment. In vitro experiments demonstrated that SIRT1 overexpression and endothelial nitric oxide synthase agonist YC-1 improved LSECs function and inhibited HSCs activation, mediated by nitric oxide. Similarly, downregulated hepatocytes SIRT1 and LSECs dysfunction were observed in the livers of aged individuals compared to young individuals and were more pronounced in aged patients with liver fibrosis. Conclusions: Aging aggravates liver fibrosis through downregulated hepatocytes SIRT1-induced LSECs dysfunction, providing a prospective curative approach for preventing and treating liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Aging aggravates liver fibrosis through downregulated hepatocyte SIRT1-induced liver sinusoidal endothelial cell dysfunction

Dai,

Qing,

Jiang

et al. 2023

Hepatology Communications

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“…Deletion of Hmgb1 gene in hepatocytes also enhanced Lxrα and Pparγ expression. In contrast, Hmgb1 overexpression in liver protected mice from HFD-induced hepatic steatosis [ 66 ].…”

Section: Gastrointestinal Ev-containing Substances Are Associated Wit...mentioning

confidence: 99%

Potential Mechanisms of Gut-Derived Extracellular Vesicle Participation in Glucose and Lipid Homeostasis

Feng

Zhang

2022

Genes

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The intestine participates in the regulation of glucose and lipid metabolism in multiple facets. It is the major site of nutrient digestion and absorption, provides the interface as well as docking locus for gut microbiota, and harbors hormone-producing cells scattered throughout the gut epithelium. Intestinal extracellular vesicles are known to influence the local immune response, whereas their roles in glucose and lipid homeostasis have barely been explored. Hence, this current review summarizes the latest knowledge of cargo substances detected in intestinal extracellular vesicles, and connects these molecules with the fine-tuning regulation of glucose and lipid metabolism in liver, muscle, pancreas, and adipose tissue.

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“…However, miR-206 was decreased in the livers of mice fed an HFD, and increasing miR-206 in the liver played a protective role in inhibiting lipid production ( 92 ). In addition, the increase in Lxrα could protect against hepatic steatosis ( 94 ). This is contradictory, but it also shows the multidirectional regulation of miR-206.…”

Section: Role Of Mirnas In Lipid Metabolism In Offspringmentioning

confidence: 99%

Non-coding RNAs: The link between maternal malnutrition and offspring metabolism

Zeng

Zhang

et al. 2022

Front. Nutr.

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Early life nutrition is associated with the development and metabolism in later life, which is known as the Developmental Origin of Health and Diseases (DOHaD). Epigenetics have been proposed as an important explanation for this link between early life malnutrition and long-term diseases. Non-coding RNAs (ncRNAs) may play a role in this epigenetic programming. The expression of ncRNAs (such as long non-coding RNA H19, microRNA-122, and circular RNA-SETD2) was significantly altered in specific tissues of offspring exposed to maternal malnutrition. Changes in these downstream targets of ncRNAs lead to abnormal development and metabolism. This review aims to summarize the existing knowledge on ncRNAs linking the maternal nutrition condition and offspring metabolic diseases, such as obesity, type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD).

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Nuclear HMGB1 protects from nonalcoholic fatty liver disease through negative regulation of liver X receptor

Cited by 7 publications

References 69 publications

Aging aggravates liver fibrosis through downregulated hepatocyte SIRT1-induced liver sinusoidal endothelial cell dysfunction

Aging aggravates liver fibrosis through downregulated hepatocyte SIRT1-induced liver sinusoidal endothelial cell dysfunction

Potential Mechanisms of Gut-Derived Extracellular Vesicle Participation in Glucose and Lipid Homeostasis

Non-coding RNAs: The link between maternal malnutrition and offspring metabolism

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