Cidea promotes hepatic steatosis by sensing dietary fatty acids

Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Hepatology (Impact Factor: 11.06). 07/2012; 56(1):95-107. DOI: 10.1002/hep.25611
Source: PubMed


High levels of dietary saturated fat have been closely associated with the development of hepatic steatosis, but the factors that mediate this process remain elusive. Here, we observed that the level of cell death-inducing DNA fragmentation factor-alpha-like effector a (Cidea) expression was highly correlated with the severity of hepatic steatosis in humans. Overexpression of Cidea in mouse liver resulted in increased hepatic lipid accumulation and the formation of large lipid droplets (LDs). In contrast, mice with a Cidea deficiency had decreased lipid accumulation and alleviated hepatic steatosis when they received a high-fat-diet feeding or in ob/ob mice. Furthermore, the knockdown of Cidea in livers of ob/ob mice resulted in significantly reduced hepatic lipid accumulation and smaller LDs. Importantly, we observed that Cidea expression in hepatocytes was specifically induced by saturated fatty acids (FAs), and such induction was reduced when sterol response element-binding protein (SREBP)1c was knocked down. In contrast, the overexpression of SREBP1c restored the saturated FA-induced expression of Cidea. In addition, we observed that the stability of Cidea protein in hepatocytes increased significantly in response to treatment with FAs. CONCLUSION: Cidea plays critical roles in promoting hepatic lipid accumulation and in the development of hepatic steatosis by acting as a sensor that responds to diets that contain FAs.

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    • "ALD are suspected to be significant and comparable with those in metabolic disorder-related fatty liver. CIDE-A CIDE-A, of which expression is regulated by SREBP-1c, is one of the factors in hepatosteatosis caused by high fat diet [43] [44]. The association of obesity with increased risk of ALD supports a likely association but additional studies are needed. "
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    ABSTRACT: Steatosis is a characteristic morphological change of alcoholic liver disease, but its pathologic significance is still obscure. Regardless of cell types, intracellular lipid droplets are coated with a phospholipid monolayer, on which many kinds of lipid droplet-associated proteins are present. These proteins, such as the perilipin family of proteins and the cell death inducing DNA fragmentation factor (DFF) 45-like effectors, are recognized to play important roles in lipid metabolism in the physiological settings. In addition, recent lipidology studies have revealed that expression of the lipid droplet-associated proteins possibly participate in the pathologic processes of many metabolic disorders, including fatty liver and insulin resistance. Hence, controlling protein expressions is expected to offer novel therapeutic options. In this review, we summarize collected data concerning the potential contribution of the lipid droplet-associated proteins to the development of alcoholic fatty liver. Without exception, existing data indicates that the lipid droplet-associated proteins, especially the perilipin family proteins, are important factors in alcoholic fatty liver. These proteins exert a prosteatotic effect, and their expression is closely associated with lipotox-icity based on endoplasmic reticulum stress and oxidative injury. Although suppression of their expression may be beneficial, careful consideration is required because these proteins simultaneously function as protective factors against lipotoxicity.
    Full-text · Article · Aug 2015 · International journal of clinical and experimental pathology
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    • "To examine NAFLD development in the INT-fed animals at a molecular level in more detail, we analyzed the expression of genes involved in lipid droplet formation, which are known to be highly correlated with the severity of NAFLD [30] [31] [32]. Q-PCR analysis was performed on all mice of all four intervention groups for cell death-inducing DFFA-like effector A (Cidea) and C (Cidec), monoacylglycerol O-acyltransferase 1 (Mogat1), and fibroblast growth factor 21 (Fgf21; Fig. 3B). "
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    ABSTRACT: ScopeWe investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet.Methods and resultsNine-week-old male C57BL/6J mice received either a (i) control (C), (ii) 30E% calorie restricted (CR), (iii) MF (25E% fat), or (iv) intermittent (INT) diet, a diet alternating weekly between 40E% CR and an ad libitum MF diet until sacrifice at the age of 12 months. The metabolic, morphological, and molecular features of NAFLD were examined. The INT diet resulted in healthy metabolic and morphological features as displayed by the continuous CR diet: glucose tolerant, low hepatic triglyceride content, low plasma alanine aminotransferase. In contrast, the C- and MF-exposed mice with high body weight developed signs of NAFLD. However, the gene expression profiles of INT-exposed mice differed to those of CR-exposed mice and showed to be more similar with those of C- and MF-exposed mice with a comparable body weight.Conclusions Our study reveals that the INT diet maintains metabolic health and reverses the adverse effects of the MF diet, thus effectively prevents the development of NAFLD in 12-month-old male C57BL/6J mice.
    Full-text · Article · Dec 2014 · Molecular Nutrition & Food Research
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    • "Increased hepatic mRNA expression of Cidea and Cidec was present in WW offspring indicative of abnormal elevation of lipid droplet formation. Cidea mRNA expression has been shown to be highly correlated with the development of hepatic steatosis in humans (Zhou et al. 2012). CIDEC also mediated the development of hepatic steatosis (Matsusue et al. 2008 "
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    Full-text · Article · Nov 2013 · Acta Physiologica
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