Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease

Donnelly, Kerry L.; Smith, Coleman I.; Schwarzenberg, Sarah Jane; Jessurun, José; Boldt, Mark D.; Parks, Elizabeth J.

doi:10.1172/jci23621

Cited by 2,920 publications

(1,819 citation statements)

References 48 publications

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“…Recently published data from patients with severe insulin resistance due to lipodystrophy or the loss of function mutations in the insulin receptor gene itself (INSR) suggest that metabolic dyslipidaemia is due in part to increased hepatic lipogenesis driven by hyperinsulinaemia. This also appears to be true in obese patients with fatty liver (Donnelly et al 2005) and in diabetic offspring (Petersen et al 2007). After binding to the insulin receptor, insulin action is mediated by a complex, incompletely understood branching signalling network.…”

Section: Pathogenesis Of Hepatic Steatosismentioning

confidence: 94%

Lipodystrophy: metabolic insights from a rare disorder

Huang-Doran¹,

Sleigh²,

Rochford³

et al. 2010

Journal of Endocrinology

183

147

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Obesity, insulin resistance and their attendant complications are among the leading causes of morbidity and premature mortality today, yet we are only in the early stages of understanding the molecular pathogenesis of these aberrant phenotypes. A powerful approach has been the study of rare patients with monogenic syndromes that manifest as extreme phenotypes. For example, there are striking similarities between the biochemical and clinical profiles of individuals with excess fat (obesity) and those with an abnormal paucity of fat (lipodystrophy), including severe insulin resistance, dyslipidaemia, hepatic steatosis and features of hyperandrogenism. Rare lipodystrophy patients therefore provide a tractable genetically defined model for the study of a prevalent human disease phenotype. Indeed, as we review herein, detailed study of these syndromes is beginning to yield valuable insights into the molecular genetics underlying different forms of lipodystrophy, the essential components of normal adipose tissue development and the mechanisms by which disturbances in adipose tissue function can lead to almost all the features of the metabolic syndrome.

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Section: Pathogenesis Of Hepatic Steatosismentioning

confidence: 94%

Lipodystrophy: metabolic insights from a rare disorder

Huang-Doran¹,

Sleigh²,

Rochford³

et al. 2010

Journal of Endocrinology

183

147

View full text Add to dashboard Cite

show abstract

“…Serum FFA levels are elevated in all of these disorders [16] . It was reported that the main source for TG in hepatocytes was derived from circulating FFAs in NAFLD [17] . Although we did not analyze serum fatty acid levels in our study, down-regulation of miR-99a in NASH was concordant with this evidence.…”

Section: ) and Further Confirmed By Sam Test (Q < 5%)mentioning

confidence: 99%

Circulating microRNAs in patients with non-alcoholic fatty liver disease

Celıkbılek¹,

Başkol²,

Taheri³

et al. 2014

WJH

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AIM:To identify novel non-invasive biomarkers for non-alcoholic fatty liver disease (NAFLD). METHODS:Twenty patients with histologically proven NAFLD and 20 controls were included. All NAFLD cases were scored using the NAFLD activity score. The relative expressions of miR-197, miR-146b, miR-10b, miR181d, miR-34a, miR-122, miR-99a and miR-29a were analyzed using real-time polymerase chain reaction. RESULTS:Serum levels of miR-181d, miR-99a, miR-197 and miR-146b were significantly lower in biopsy-proven NAFLD patients than in the healthy controls. Serum levels of miR-197 and miR-10b were inversely correlated with degree of inflammation and miR-181d and miR99a were inversely correlated with serum gamma glutamyl transferase levels in non-alcoholic steatohepatitis patients. CONCLUSION:NAFLD is associated with altered serum miRNA expression pattern. This study provides clues for defining the non-invasive diagnosis of NAFLD.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; MicroRNA; Noninvasive; Serum markers Core tip: Due to the limitations of liver biopsy, the use of non-invasive markers has emerged in recent years. MicroRNAs (miRNAs) are a class of naturally occurring small noncoding RNAs that regulate gene expression. Altered miRNA expression has been reported in animal and human liver samples in non-alcoholic fatty liver disease (NAFLD). There is, however, only limited information on their detection in blood and their correlation with histological disease severity in patients with NAFLD. For this reason, we measured the serum levels of some miRNAs in non-alcoholic steatohepatitis (NASH) patients. Of these microRNAs, miR-181d, miR99a, miR-197 and miR-146b were expressed at lower levels in NASH patients than in controls. Serum levels of miR-197 and miR-10b were inversely correlated with degree of inflammation and miR-181d and miR-99a were inversely correlated with serum gamma glutamyl transferase levels in NASH patients. Circulating microRNAs in patients with non-alcoholic fatty liver disease 613 Celikbilek M, Baskol M, Taheri S, Deniz K, Dogan S, Zararsız G, Gursoy S, Guven K, Ozbakır O, Dundar M, Yucesoy M. Circulating microRNAs in patients with non-alcoholic fatty liver disease. ORIGINAL ARTICLE

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“…In this context, TG accumulation > 55 mg/g measured by MRI or by histological examination is its key diagnostic feature [12,13] . Fatty acids (FA) account for approximately 60% of TG in the liver of NAFLD patients, while approximately 15% originate from dietary fat [14] . De novo production is responsible for the rest 25% [14] .…”

Section: Introductionmentioning

confidence: 99%

“…Fatty acids (FA) account for approximately 60% of TG in the liver of NAFLD patients, while approximately 15% originate from dietary fat [14] . De novo production is responsible for the rest 25% [14] . Insulin resistance plays a key role in the pathogenesis of NAFLD [2,15,16] .…”

Section: Introductionmentioning

confidence: 99%

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Kostapanos

Kei²,

Elisaf³

2013

WJH

131

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Non-alcoholic fatty liver disease (NAFLD) is a common health problem with a high mortality burden due to its liver-and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). Impaired hepatic fatty acid (FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors (PPARs) are involved in lipid and glucose metabolic pathways. The novel concept is that the activation of the PPARα subunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis pathogenesis. These include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet, T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were absent. In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.

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Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease

Cited by 2,920 publications

References 48 publications

Lipodystrophy: metabolic insights from a rare disorder

Lipodystrophy: metabolic insights from a rare disorder

Circulating microRNAs in patients with non-alcoholic fatty liver disease

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

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