Alcohol metabolites and lipopolysaccharide: Roles in the development and/or progression of alcoholic liver disease

Schaffert, Courtney S.; Duryee, Michael J.; Hunter, Carlos D.; Hamilton, Bartlett C.; DeVeney, Amy L.; Huerter, Mary M.; Klassen, Lynell Warren; Thiele, Geoffrey M.

doi:10.3748/wjg.15.1209

Cited by 66 publications

(49 citation statements)

References 69 publications

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“…4). This is an important distinction from rodents, in which fibrosis only occurs in fatty liver disease models that are administered an additional injury [83][84][85] or lengthy treatment. 86,87 Further, these findings highlight the value of the zebrafish model for studying HSC biology as there is a robust response after Tm and EtOH administration.…”

Section: Discussionmentioning

confidence: 99%

Defining Hepatic Dysfunction Parameters in Two Models of Fatty Liver Disease in Zebrafish Larvae

et al. 2013

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Fatty liver disease in humans can progress from steatosis to hepatocellular injury, fibrosis, cirrhosis, and liver failure. We developed a series of straightforward assays to determine whether zebrafish larvae with either tunicamycin-or ethanol-induced steatosis develop hepatic dysfunction. We found altered expression of genes involved in acute phase response and hepatic function, and impaired hepatocyte secretion and disruption of canaliculi in both models, but glycogen deficiency in hepatocytes and dilation of hepatic vasculature occurred only in ethanol-treated larvae. Hepatic stellate cells (HSCs) become activated during liver injury and HSC numbers increased in both models. Whether the excess lipids in hepatocytes are a direct cause of hepatocyte dysfunction in fatty liver disease has not been defined. We prevented ethanol-induced steatosis by blocking activation of the sterol response element binding proteins (Srebps) using gonzo mbtps1 mutants and scap morphants and found that hepatocyte dysfunction persisted even in the absence of lipid accumulation. This suggests that lipotoxicity is not the primary cause of hepatic injury in these models of fatty liver disease. This study provides a panel of parameters to assess liver disease that can be easily applied to zebrafish mutants, transgenics, and for drug screening in which liver function is an important consideration.

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Section: Discussionmentioning

confidence: 99%

Defining Hepatic Dysfunction Parameters in Two Models of Fatty Liver Disease in Zebrafish Larvae

et al. 2013

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“…In fact, the gut-liver axis is the route by which bacteria and their potential hepatotoxic products, like LPS, can easily reach the liver. [159][160][161] Ultimately, pro-inflammatory cytokine (e.g. interleukin: IL-1 and IL-8) production plays a pivotal role in the induction and progression of nonalcoholic liver disease to NASH and cirrhosis.…”

Section: Nonalcoholic Fatty Liver Diseasementioning

confidence: 99%

Exploring the microbiome in health and disease

Scotti

Boué

Sasso

et al. 2017

Toxicology Research and Application

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The analysis of human microbiome is an exciting and rapidly expanding field of research. In the past decade, the biological relevance of the microbiome for human health has become evident. Microbiome comprises a complex collection of microorganisms, with their genes and metabolites, colonizing different body niches. It is now well known that the microbiome interacts with its host, assisting in the bioconversion of nutrients and detoxification, supporting immunity, protecting against pathogenic microbes, and maintaining health. Remarkable new findings showed that our microbiome not only primarily affects the health and function of the gastrointestinal tract but also has a strong influence on general body health through its close interaction with the nervous system and the lung. Therefore, a perfect and sensitive balanced interaction of microbes with the host is required for a healthy body. In fact, growing evidence suggests that the dynamics and function of the indigenous microbiota can be influenced by many factors, including genetics, diet, age, and toxicological agents like cigarette smoke, environmental contaminants, and drugs. The disruption of this balance, that is called dysbiosis, is associated with a plethora of diseases, including metabolic diseases, inflammatory bowel disease, chronic obstructive pulmonary disease, periodontitis, skin diseases, and neurological disorders. The importance of the host microbiome for the human health has also led to the emergence of novel therapeutic approaches focused on the intentional manipulation of the microbiota, either by restoring missing functions or eliminating harmful roles. In the present review, we outline recent studies devoted to elucidate not only the role of microbiome in health conditions and the possible link with various types of diseases but also the influence of various toxicological factors on the microbial composition and function.

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“…The activation of liverresident macrophages or Kupffer cells, at least in part by increased exposure to gut-derived bacterial wall components such as endotoxins, results in the increased production of proinflammatory cytokines (Wree et al 2013;Lewis and Mohanty 2010) and numerous other factors. These factors include products of ethanol-induced inflammation, ethanol metabolism, and the indirect reactions stimulated by ethanol metabolites (Schaffert et al 2009). Several studies (Albano 2006;Viitala et al 2000;) have demonstrated relationships between ALD, the inflammatory response, and oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Association between circulating inflammatory molecules and alcoholic liver disease in men

Jia³

et al. 2016

Cell Stress and Chaperones

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The association between alcoholic liver disease (ALD) and the inflammatory response remains controversial. The aim of this study was to explore this association between ALD and inflammation. We enrolled 214 male participants, who were divided into three age-matched groups: ALD (n = 135), chronic alcohol ingestion without ALD (non-ALD; n = 42), and control (n = 37). The BMI was significantly higher in the ALD group than in the non-ALD and control groups (all P = 0.000). Further, the constituent ratio of the liver inflammatory level was significantly higher in the ALD group than in the non-ALD and control groups (P = 0.002 and P = 0.000, respectively). In addition, the median serum ALT, AST, and GGT levels were significantly higher in the ALD group than in the control group (P = 0.023, P = 0.008, and P = 0.000, respectively); these levels were also significantly higher in the ALD group than in the non-ALD group (P = 0.013, P = 0.010, and P = 0.000, respectively). The median serum CRP level was significantly higher in the ALD group than in the non-ALD and control groups (P = 0.006 and P = 0.000, respectively). Further, the median serum TNF-α level was significantly lower in the ALD group than in the non-ALD and control groups (P = 0.004 and P = 0.000, respectively). The median serum sOX40L and HSP70 levels were significantly lower in the ALD group than in the control group (P = 0.008 and P = 0.018, respectively). In addition, the ALT, AST, and GGT levels were positively correlated with the CRP level (r = 0.211, P = 0.002; r = 0.220, P = 0.001 and r = 0.295, P = 0.000, respectively), and the GGT level was negatively correlated with the TNF-α (r = −0.225, P = 0.001), sOX40L (r = −0.165, P = 0.016), and HSP70 levels (r = −0.178, P = 0.009). Further, the Cr level was negatively correlated with the IL-10 level (r = −0.166, P = 0.015). Logistic regression analysis verified that the BMI (OR = 1.637, 95%CI: 1.374-1.951, P = 0.000) and GGT level were significantly higher (OR = 1.039, 95%CI: 1.020-1.059, P = 0.000) and that the TNF-α (OR = 0.998, 95%CI: 0.996-1.000, P = 0.030) and HSP70 levels were significantly lower (OR = 1.017, 95%CI: 1.003-1.031, P = 0.029) in the ALD group than in the non-ALD group. Further, the moderate-to-severe ALD patients had a significantly higher serum CRP level (Or = 1.349, 95%CI: 1.066-1.702, P = 0.013) and significantly lower HSP60 (OR = 0.965, 95%CI: 0.938-0.993, P = 0.014) and HSP70 levels (OR = 0.978, 95%CI: 0.962-0.995, P = 0.010) than the mild ALD patients. These results suggest that ALD patients may present with obesity, liver damage, and an imbalanced inflammatory immune response, mainly manifesting as decreased levels of immune inflammatory cytokines. In addition, they suggest that certain liver and kidney function parameters and ALD severity are either positively or negatively correlated with certain inflammatory cytokines. Hence, ALD patients may be at increased risks of obesity-and inflammation-related diseases. Accordingly, to control the inflammatory response, preventativ...

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Alcohol metabolites and lipopolysaccharide: Roles in the development and/or progression of alcoholic liver disease

Cited by 66 publications

References 69 publications

Defining Hepatic Dysfunction Parameters in Two Models of Fatty Liver Disease in Zebrafish Larvae

Defining Hepatic Dysfunction Parameters in Two Models of Fatty Liver Disease in Zebrafish Larvae

Exploring the microbiome in health and disease

Association between circulating inflammatory molecules and alcoholic liver disease in men

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