The role of NAFLD in cardiometabolic disease: an update

Faasse, Sarah A.; Braun, Hayley; Vos, Miriam B.

doi:10.12688/f1000research.12028.1

Cited by 18 publications

(19 citation statements)

References 54 publications

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“…Non-alcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease in developed countries worldwide [1,2]. NAFLD is considered to be the hepatic manifestation of the metabolic syndrome [3].…”

Section: Introductionmentioning

confidence: 99%

Why Bile Acids Are So Important in Non-Alcoholic Fatty Liver Disease (NAFLD) Progression

Gottlieb

Canbay

2019

Cells

103

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Non-alcoholic fatty liver disease (NAFLD) is a complex disease, affecting not just the liver, but also all other organs in the body. Despite an increasing amount of people worldwide developing NAFLD and having it progress to non-alcoholic steatohepatitis (NASH) and potentially cirrhosis, there is still no approved therapy. Therefore, huge efforts are being made to find and develop a successful treatment. One of the special interests is understanding the liver–gut axis and especially the role of bile acids in the progression of NAFLD. Farnesoid X receptor (FXR)-agonists have been approved und used in other liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), and have shown signs of being able to decrease inflammation and potentially steatosis. This review will mainly focus on targets/ligands that play an important role in bile acid metabolism and give an overview of ongoing clinical as well as pre-clinical trials. With the complexity of the issue, we did not aim at giving a complete review, rather highlighting important targets and potential treatments that could be approved for NAFLD/NASH treatment within the next few years.

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Section: Introductionmentioning

confidence: 99%

Why Bile Acids Are So Important in Non-Alcoholic Fatty Liver Disease (NAFLD) Progression

Gottlieb

Canbay

2019

Cells

103

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“…Chronic hypoxia has been identified as a major contributor to liver injury as a response to obstructive sleep apnea (OSA) . This has been to the cardio metabolic syndrome and NAFLD . A study on mice by Savransky et al found that chronic intermittent hypoxia when combined with a high‐fat diet (HFD) induced inflammation and lipid peroxidation, with the hypoxia exposure group showing increased steatosis .…”

Section: Introductionmentioning

confidence: 99%

Hypoxia inducible factor‐1 promotes liver fibrosis in nonalcoholic fatty liver disease by activating PTEN/p65 signaling pathway

Han

Zhao

et al. 2019

J of Cellular Biochemistry

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Obesity is a major contributor to the development of steatohepatitis and fibrosis from nonalcoholic fatty liver disease (NAFLD). Hypoxia aggravates progression of NAFLD. In mice on high‐fat diet (HFD), hepatic steatosis leads to liver tissue hypoxia, evidenced by accumulation of hypoxia inducible factor‐1‐alpha (HIF‐1α), which is a central regulator of the global response to hypoxia. Hepatocyte cell signaling is an important factor in hepatic fibrogenesis. We here hypothesize that HIF‐1α knockout in hepatocyte may protect against liver fibrosis. We first found that HFD led to 80% more hepatic collagen deposition than Hif1a−/−hep mice, which was confirmed by a‐SMA staining of liver tissue. Body weight and liver weight were similar between groups. We then found the increasing HIF1a expression and decreasing PTEN expression in the mice on HFD and in PA‐treated HepG2 cells. Finally, we found that HIF1 mediated PTEN/nfkb‐p65 pathway plays an important role in the development of NAFLD to liver fibrosis. Collectively, these results identify a novel HIF1a/PTEN/NF‐κ Bp65 signaling pathway in NAFLD, which could be targeted for the therapy.

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“…1 The prevalence of NAFLD has markedly increased over the last years, concomitantly with increases in the prevalence of both obesity and the metabolic syndrome. 2 The global prevalence of NAFLD is currently estimated to be 25% with the highest prevalence in the Middle East and South America and the lowest in Africa. 3 Using an elevated fatty liver index (FLI), a validated proxy of NAFLD, 4,5 a similar prevalence of NAFLD was reported in a large North European cohort.…”

Section: Introductionmentioning

confidence: 99%

Nonalcoholic fatty liver disease, circulating ketone bodies and all‐cause mortality in a general population‐based cohort

Post

Garcia

Berg

et al. 2021

Eur J Clin Investigation

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Background: Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent, paralleling the obesity epidemic. Ketone bodies are produced in the liver, but it is currently uncertain whether circulating ketone bodies are increased in the context of NAFLD. We investigated the association between NAFLD and circulating ketone bodies and determined the extent to which NAFLD and circulating ketone bodies are associated with all-cause mortality. Methods: Plasma ketone bodies were measured by nuclear magnetic resonance spectroscopy in participants of the general population-based PREVEND study. A fatty liver index (FLI) ≥60 was regarded as a proxy of NAFLD. Associations of an elevated FLI and ketone bodies with all-cause mortality were investigated using Cox regression analyses. Results:The study included 6,297 participants aged 54 ± 12 years, of whom 1,970 (31%) had elevated FLI. Participants with elevated FLI had higher total ketone bodies (194 [153-259] vs 170 µmol/L; P < .001) than participants without elevated FLI. During 7.9 [7.8-8.9] years of follow-up, 387 (6%) participants died. An elevated FLI was independently associated with an increased risk of mortality (HR:1.34 [1.06-1.70]; P = .02). Higher total ketone bodies were also associated with an increased mortality risk (HR per doubling: 1.29 [1.12-1.49]; P < .001). Mediation analysis suggested that the association of elevated FLI with all-cause mortality was in part mediated by ketone bodies (proportion mediated: 10%, P < .001). Conclusion: Circulating ketone bodies were increased in participants with suspected NAFLD. Both suspected NAFLD and higher circulating ketone bodies are associated with an increased risk of all-cause mortality.

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The role of NAFLD in cardiometabolic disease: an update

Cited by 18 publications

References 54 publications

Why Bile Acids Are So Important in Non-Alcoholic Fatty Liver Disease (NAFLD) Progression

Why Bile Acids Are So Important in Non-Alcoholic Fatty Liver Disease (NAFLD) Progression

Hypoxia inducible factor‐1 promotes liver fibrosis in nonalcoholic fatty liver disease by activating PTEN/p65 signaling pathway

Nonalcoholic fatty liver disease, circulating ketone bodies and all‐cause mortality in a general population‐based cohort

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