If steatosis is the atherosclerosis of the liver, are statins the “aspirin” for steatosis?

Lonardo, Amedeo; Loria, Paola

doi:10.1016/j.dld.2012.02.020

Cited by 12 publications

(6 citation statements)

References 18 publications

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“…In the meantime, from the perspective of clinical practice, the notion that NAFLD is a powerful trigger and amplifier of adverse CVD outcomes can justify targeting NAFLD in the attempt to reduce the risk of incident CVD (as schematically summarized in Figure 3) [2][3][4][5]66,91,[144][145][146][147][148].…”

Section: Discussionmentioning

confidence: 99%

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Non-alcoholic fatty liver disease and risk of cardiovascular disease

et al. 2016

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Section: Discussionmentioning

confidence: 99%

“…Based on data presented in this manuscript and on further published evidence [2][3][4][5]91,[143][144][145][146][147], this cartoon summarizes how lifestyle and drug interventions might mechanistically reduce CVD risk by targeting various aspects of NAFLD pathogenesis and histology. …”

Section: Subcellular Localizationmentioning

confidence: 95%

Non-alcoholic fatty liver disease and risk of cardiovascular disease

et al. 2016

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“…NAFLD is a complex disorder and is recognized as the hepatic manifestation of metabolic syndrome and insulin resistance [26,27]. It is considered as a progressive liver disease which has the potential to progress to cirrhosis and hepatocellular carcinoma (HCC).…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Ameliorates Liver Fibrosis via Mediating Nitric Oxide Synthase in Rats with Non-Alcoholic Steatohepatitis-Related Liver Fibrosis

et al. 2013

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BackgroundSimvastatin exerts pleiotropic effects on cardiovascular system. However, its effect on non-alcoholic fatty liver disease, especially the liver fibrosis, remains obscure. We aimed to clarify the relationship between simvastatin and liver fibrosis both in vivo and in vitro.MethodsA High-fat diet was given to establish rat models with non-alcoholic steatohepatitis (NASH)-related liver fibrosis and simvastatin (4mg·kg-1·d-1) was administrated intragastrically until hepatic histological findings confirmed the appearance of fibrosis. Human hepatic stellate cell (HSC) line lx-2 cells were cultured in an adipogenic differentiating mixture (ADM) and then were treated with transforming growth factorβ1 (TGF-β1), served as a positive control, simvastatin, TGF-β1 plus simvastatin, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, a inhibitor of nitric oxide synthase), and L-NAME plus simvastatin, respectively. The expressions of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and Collagen І as well as cellular α-smooth muscle actin (α-SMA) were measured by real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot in liver tissue and HSC.ResultsWith the progress of NASH-related fibrosis, hepatic mRNA and protein expressions of iNOS, α-SMA, and Collagen І were increased while those of eNOS were decreased. Compared with model rats in 24th week group, rats in simvastatin group had less expressions of iNOS, α-SMA, and Collagen І and more expressions of eNOS. In vitro, LX-2 cells acquired quiescent phenotype when cultured in ADM, and TGF-β1 could activate the quiescent HSC. Simvastatin inhibited LX-2 cells activation due to TGF-β1 or L-NAME by increasing the expression of eNOS and decreasing the expression of iNOS.ConclusionsSimvastatin improves the prognosis of NASH-related fibrosis by increasing the expression of eNOS, decreasing the expression of iNOS, and inhibiting the activation of HSC.

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“…In addition to their effects on blood lipids, these drugs are able to reduce tumor necrosis factor alpha, an inflammatory cytokine. However, although ameliorating surrogate markers, statins are not considered to have a convincing effect in nonalcoholic fatty liver disease 105. Moreover, some caution is advised, given that statins are prone to augmenting the risk of diabetes 106…”

Section: Treatmentmentioning

confidence: 99%

Hepatic function and the cardiometabolic syndrome

Wiernsperger

2013

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Despite skeletal muscle being considered by many as the source of insulin resistance, physiology tells us that the liver is a central and cardinal regulator of glucose homeostasis. This is sometimes underestimated because, in contrast with muscle, investigations of liver function are technically very difficult. Nevertheless, recent experimental and clinical research has demonstrated clearly that, due in part to its anatomic position, the liver is exquisitely sensitive to insulin and other hormonal and neural factors, either by direct intrahepatic mechanisms or indirectly by organ cross-talk with muscle or adipose tissue. Because the liver receives absorbed nutrients, these have a direct impact on liver function, whether via a caloric excess or via the nature of food components (eg, fructose, many lipids, and trans fatty acids). An emerging observation with a possibly great future is the increase in intestinal permeability observed as a consequence of high fat intake or bacterial modifications in microbiota, whereby substances normally not crossing the gut gain access to the liver, where inflammation, oxidative stress, and lipid accumulation leads to fatty liver, a situation observed very early in the development of diabetes. The visceral adipose tissue located nearby is another main source of inflammatory substances and oxidative stress, and also acts on hepatocytes and Kupffer cells, resulting in stimulation of macrophages. Liberation of these substances, in particular triglycerides and inflammation factors, into the circulation leads to ectopic fat deposition and vascular damage. Therefore, the liver is directly involved in the development of the prediabetic cardiometabolic syndrome. Treatments are mainly metformin, and possibly statins and vitamin D. A very promising avenue is treatment of the leaky gut, which appears increasingly to be an important causal factor in hepatic insulin resistance and steatosis.

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If steatosis is the atherosclerosis of the liver, are statins the “aspirin” for steatosis?

Cited by 12 publications

References 18 publications

Non-alcoholic fatty liver disease and risk of cardiovascular disease

Non-alcoholic fatty liver disease and risk of cardiovascular disease

Simvastatin Ameliorates Liver Fibrosis via Mediating Nitric Oxide Synthase in Rats with Non-Alcoholic Steatohepatitis-Related Liver Fibrosis

Hepatic function and the cardiometabolic syndrome

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