Association between serum free fatty acid levels and nonalcoholic fatty liver disease: a cross-sectional study

Zhang, Juanwen; Zhao, Ying; Xu, Chengfu; Hong, Yani; Lu, Huanle; Wu, Jianping; Chen, Yu

doi:10.1038/srep05832

Cited by 141 publications

(117 citation statements)

References 56 publications

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“…In the postprandial state, a reduction in the antilipolytic action of insulin, leading to elevated serum FFA and glycerol, takes place (85). In humans, venous drainage of visceral adipose tissue is via the portal vein, which provides FFA and glycerol as substrates for hepatic lipid and glucose metabolism (266,290,355), while the increased lipolysis in the retroperitoneal and epididymal fat depots constitutes the main source for these metabolites for hepatic metabolism in rodents (92, 311). The elevated concentrations of FFA reduce the degradation of apolipoprotein B and insulin, which may contribute to the development of the dyslipidemia, hyperinsulinemia, and insulin resistance observed in visceral obesity (178,262,328).…”

Section: Recruitment Of Proinflammatory Immune Cells In Obesity Perpementioning

confidence: 99%

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Rodrı́guez

Ezquerro

Méndez‐Giménez

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

235

186

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Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance for the identification of pharmacological targets for the treatment of obesity and its associated metabolic diseases. white and brown adipogenesis; fat browning; adipocyte hypertrophy and hyperplasia; adipose tissue inflammation; extracellular matrix remodeling THE ADIPOSE ORGAN REPRESENTS a special loose connective tissue containing adipocytes and several cell types surrounded by capillary and innervation networks (47, 79, 82). Adipocytes comprise ϳ35-70% of adipose mass, and the other cell types found in the stroma-vascular fraction include preadipocytes, mesenchymal stem cells, macrophages and other immune cells, and endothelial and smooth muscle cells, among others (79). The classical functions of adipose tissue are the storage of energy in the form of triacylglycerols (TG) and as thermal insulator. Adipocytes were formerly classified into two main types: white adipocytes, which store energy in the form of fat, and brown adipocytes, which induce thermogenesis (82). The current classification scheme includes a third category of adipocytes, termed beige or brite (brown-in-white) adipocytes, which can be considered inducible brown-like cells with thermogenic properties (340). Since the identification of leptin in 1994 (359), adipose tissue has emerged as an extremely active endocrine organ that secretes a huge variety of hormones, cytokines, growth factors, and vasoactive factors that are collectively termed adipokines (67, 81,235,262). Over the last three decades, overwhelming evidence has proven that adipokines not only influence adipobiol...

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Section: Recruitment Of Proinflammatory Immune Cells In Obesity Perpementioning

confidence: 99%

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Rodrı́guez

Ezquerro

Méndez‐Giménez

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

235

186

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“…Excessive TG deposition in hepatocytes derives from an increased delivery of FFA into the liver, leading to the development of NAFLD [3]. In obesity-associated NAFLD, FFA delivery to the liver is increased, especially during the fed state, due to adipose tissue insulin resistance [4].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-122 Inhibits Lipid Droplet Formation and Hepatic Triglyceride Accumulation via Yin Yang 1

Chen²,

Chen³

et al. 2017

Cell Physiol Biochem

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Background/Aims: An increase in intracellular lipid droplet formation and hepatic triglyceride (TG) content usually results in nonalcoholic fatty liver disease. However, the mechanisms underlying the regulation of hepatic TG homeostasis remain unclear. Methods: Oil red O staining and TG measurement were performed to determine the lipid content. miRNA expression was evaluated by quantitative PCR. A luciferase assay was performed to validate the regulation of Yin Yang 1 (YY1) by microRNA (miR)-122. The effects of miR-122 expression on YY1 and its mechanisms involving the farnesoid X receptor and small heterodimer partner (FXR-SHP) pathway were evaluated by quantitative PCR and Western blot analyses. Results: miR-122 was downregulated in free fatty acid (FFA)-induced steatotic hepatocytes, and streptozotocin and high-fat diet (STZ-HFD) induced nonalcoholic steatohepatitis (NASH) in mice. Transfection of hepatocytes with miR-122 mimics before FFA induction inhibited lipid droplet formation and TG accumulation in vitro. These results were verified by overexpressing miR-122 in the livers of STZ-HFD-induced NASH mice. The 3’-untranslated region (3’UTR) of YY1 mRNA is predicted to contain an evolutionarily conserved miR-122 binding site. In silico searches, a luciferase reporter assay and quantitative PCR analysis confirmed that miR-122 directly bound to the YY1 3’UTR to negatively regulate YY1 mRNA in HepG2 and Huh7 cells. The (FXR-SHP) signaling axis, which is downstream of YY1, may play a key role in the mechanism of miR-122-regulated lipid homeostasis. YY1-FXR-SHP signaling, which is negatively regulated by FFA, was enhanced by miR-122 overexpression. This finding was also confirmed by overexpression of miR-122 in the livers of NASH mice. Conclusions: The present results indicate that miR-122 plays an important role in lipid (particularly TG) accumulation in the liver by reducing YY1 mRNA stability to upregulate FXR-SHP signaling.

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“…The prevalence of NAFLD and NASH increases from around 20% and 3%, respectively, in the general population to 75% and 25–70%, respectively, in morbid obesity56. The excessive TG deposition in hepatocytes derives from an increased delivery of free fatty acids (FFA) into the liver from several different sources: excess dietary fat, higher FFA release from adipocytes via lipolysis, as well as increased de novo hepatic lipogenesis, ultimately leading to the development of obesity-associated NAFLD7. In addition, growing evidence indicates that hepatic mitochondrial dysfunction as well as alterations in autophagy are also involved in the development of this disease8.…”

mentioning

confidence: 99%

Acylated and desacyl ghrelin are associated with hepatic lipogenesis, β-oxidation and autophagy: role in NAFLD amelioration after sleeve gastrectomy in obese rats

Ezquerro

Méndez‐Giménez

Becerril

et al. 2016

Sci Rep

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Bariatric surgery improves non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate the potential role of ghrelin isoforms in the resolution of hepatic steatosis after sleeve gastrectomy, a restrictive bariatric surgery procedure, in diet-induced obese rats. Male Wistar rats (n = 161) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary interventions [fed ad libitum a normal (ND) or a high-fat (HFD) diet or pair-fed]. Obese rats developed hepatosteatosis and showed decreased circulating desacyl ghrelin without changes in acylated ghrelin. Sleeve gastrectomy induced a dramatic decrease of desacyl ghrelin, but increased the acylated/desacyl ghrelin ratio. Moreover, sleeve gastrectomy reduced hepatic triglyceride content and lipogenic enzymes Mogat2 and Dgat1, increased mitochondrial DNA amount and induced AMPK-activated mitochondrial FFA β-oxidation and autophagy to a higher extent than caloric restriction. In primary rat hepatocytes, the incubation with both acylated and desacyl ghrelin (10, 100 and 1,000 pmol/L) significantly increased TG content, triggered AMPK-activated mitochondrial FFA β-oxidation and autophagy. Our data suggest that the decrease in the most abundant isoform, desacyl ghrelin, after sleeve gastrectomy contributes to the reduction of lipogenesis, whereas the increased relative acylated ghrelin levels activate factors involved in mitochondrial FFA β-oxidation and autophagy in obese rats, thereby ameliorating NAFLD.

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Association between serum free fatty acid levels and nonalcoholic fatty liver disease: a cross-sectional study

Cited by 141 publications

References 56 publications

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

MicroRNA-122 Inhibits Lipid Droplet Formation and Hepatic Triglyceride Accumulation via Yin Yang 1

Acylated and desacyl ghrelin are associated with hepatic lipogenesis, β-oxidation and autophagy: role in NAFLD amelioration after sleeve gastrectomy in obese rats

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