Hepatic fat loss in advanced nonalcoholic steatohepatitis: Are alterations in serum adiponectin the cause?

Poorten, David van der; Samer, Caroline Flora; Ramezani-Moghadam, Mehdi; Coulter, Sally; Kacevska, Marina; Schrijnders, Dennis; Wu, Lindsay E.; McLeod, Duncan; Bugianesi, Elisabetta; Komuta, Mina; Roskams, Tania; Liddle, Christopher; Hebbard, Lionel; George, Jacob

doi:10.1002/hep.26072

Cited by 147 publications

(89 citation statements)

References 41 publications

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“…Recent studies demonstrated converting FFA to TG is critical in protecting the liver from FFA-induced lipotoxicity. Clinical observations reveal patients with advanced steatohepatitis express significantly reduced key hepatic lipogenic enzymes, and have increased hepatic FFA and significantly reduced hepatic TG (Nagaya et al, 2010, van der Poorten et al, 2013). Specifically, genetic interruption of hepatic TG synthesis leads to increased hepatic FFA accumulation, inflammation, fibrosis, and exacerbated liver damage (Yamaguchi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy

et al. 2016

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The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD) upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake) reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD + BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR), inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA) in the HFD + BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte.

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Section: Discussionmentioning

confidence: 99%

Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy

et al. 2016

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“…Visceral adipose tissue is also an independent risk factor for hepatic necro-inflammation and fibrosis. 141 Ethnicity modulates obesity as a risk factor for NAFLD.…”

Section: Visceral Obesitymentioning

confidence: 99%

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Lonardo

Bellentani

Argo

et al. 2015

Digestive and Liver Disease

399

318

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We aimed to illustrate the epidemiology of nonalcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published through May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidemia", "familial heterozygous hypobelipoproteinemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms".We found that age, sex and ethnicity are major physiologic modifiers of the risk of nonalcoholic fatty liver disease, along with belonging to "nonalcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of nonalcoholic fatty liver disease risk. Compared to these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of nonalcoholic fatty liver disease.A better understanding of the epidemiology of nonalcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.

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“…However, only the intermediate NFS and APRI scores between published low and high cut-offs correlated directly with the presence of steatosis by ultrasonography. The lack of significant association between the NFS or APRI scores higher than published high cut-off values and hepatic steatosis could be due to "burn-out" NASH as advanced liver fibrosis in NASH is often accompanied by a reduction in hepatic fat to the point of complete fat loss [17] . Alternatively, the lack of association might be attributed to type Ⅱ error due to the small number of participants who had high NFS or APRI scores.…”

Section: Discussionmentioning

confidence: 86%

Burden of nonalcoholic fatty liver disease and advanced fibrosis in a Texas Hispanic community cohort

Pan

Fisher‐Hoch

Chen

et al. 2015

WJH

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Hepatic fat loss in advanced nonalcoholic steatohepatitis: Are alterations in serum adiponectin the cause?

Cited by 147 publications

References 41 publications

Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy

Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Burden of nonalcoholic fatty liver disease and advanced fibrosis in a Texas Hispanic community cohort

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