scholarly journals Effective Food Ingredients for Fatty Liver: Soy Protein β-Conglycinin and Fish Oil

2018 ◽  
Vol 19 (12) ◽  
pp. 4107 ◽  
Author(s):  
Tomomi Yamazaki ◽  
Dongyang Li ◽  
Reina Ikaga
Keyword(s):  
Fatty Liver ◽  
Fish Oil ◽  
Soy Protein ◽  
De Novo ◽  
Regulatory Element ◽  
De Novo Lipogenesis ◽  
Peroxisome Proliferator ◽  
Experimental Conditions ◽  
Alcoholic Fatty Liver ◽  
Food Ingredients

Obesity is prevalent in modern society because of a lifestyle consisting of high dietary fat and sucrose consumption combined with little exercise. Among the consequences of obesity are the emerging epidemics of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor that stimulates gene expression related to de novo lipogenesis in the liver. In response to a high-fat diet, the expression of peroxisome proliferator-activated receptor (PPAR) γ2, another nuclear receptor, is increased, which leads to the development of NAFLD. β-Conglycinin, a soy protein, prevents NAFLD induced by diets high in sucrose/fructose or fat by decreasing the expression and function of these nuclear receptors. β-Conglycinin also improves NAFLD via the same mechanism as for prevention. Fish oil contains n-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. Fish oil is more effective at preventing NAFLD induced by sucrose/fructose because SREBP-1c activity is inhibited. However, the effect of fish oil on NAFLD induced by fat is controversial because fish oil further increases PPARγ2 expression, depending upon the experimental conditions. Alcohol intake also causes an alcoholic fatty liver, which is induced by increased SREBP-1c and PPARγ2 expression and decreased PPARα expression. β-Conglycinin and fish oil are effective at preventing alcoholic fatty liver because β-conglycinin decreases the function of SREBP-1c and PPARγ2, and fish oil decreases the function of SREBP-1c and increases that of PPARα.

scholarly journals A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1822
Author(s):  
Christian von Loeffelholz ◽  
Sina M. Coldewey ◽  
Andreas L. Birkenfeld
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Mammalian Cells ◽  
De Novo ◽  
Adenosine Monophosphate ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.

Adiponectin: A Key Adipokine in Alcoholic Fatty Liver

2009 ◽  
Vol 234 (8) ◽  
pp. 850-859 ◽  
Author(s):  
Min You ◽  
Christopher Q. Rogers
Keyword(s):  
Fatty Liver ◽  
De Novo ◽  
Regulatory System ◽  
Receptor Expression ◽  
Sirtuin 1 ◽  
De Novo Lipogenesis ◽  
Lipid Lowering ◽  
Acid Oxidation ◽  
Alcoholic Fatty Liver ◽  
Central Target

Alcoholic fatty liver is a major risk factor for advanced liver injuries such as steatohepatitis, fibrosis, and cirrhosis. While the underlying mechanisms are multiple, the development of alcoholic fatty liver has been attributed to a combined increase in the rate of de novo lipogenesis and a decrease in the rate of fatty acid oxidation in animal liver. Among various transcriptional regulators, the hepatic SIRT1 (sirtuin 1)-AMPK (AMPK-activated kinase) signaling system represents a central target for the action of ethanol in the liver. Adiponectin is one of the adipocyte-derived adipokines with potent lipid-lowering properties. Growing evidence has demonstrated that the development of alcoholic fatty liver is associated with reduced circulating adiponectin levels, decreased hepatic adiponectin receptor expression, and impaired hepatic adiponectin signaling. Adiponectin confers protection against alcoholic fatty liver via modulation of complex hepatic signaling pathways largely controlled by the central regulatory system, SIRT1-AMPK axis. This review aims to integrate the current research findings of ethanol-mediated dysregulation of adiponectin and its receptors and to provide a comprehensive point of view for understanding the role of adiponectin signaling in the development of alcoholic fatty liver.

scholarly journals SUN-LB52 The Protective Effects of Hepatocyte GH Receptor (GHR) Signaling Against Steatosis and Liver Injury Is Sexually Dimorphic and Autonomous of IGF1

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Andre Sarmento-Cabral ◽  
Mercedes del Rio-Moreno ◽  
Mari C Vazquez-Borrego ◽  
Mariyah Mahmood ◽  
Elena Gutierrez-Casado ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Injury ◽  
Fatty Liver ◽  
Negative Feedback ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
Chow Diet ◽  
Alcoholic Fatty Liver ◽  
Systemic Insulin Resistance

Abstract GH dysregulation contributes to the development of non-alcoholic fatty liver disease (NAFLD), however debate remains as to the relative contribution of the direct vs indirect effects of GH, via IGF1. Mouse models with congenital, liver-specific knockout of the GHR, JAK2 or STAT5, as adults exhibit steatosis, glucose intolerance, insulin resistance and white adipose tissue (WAT) lipolysis. It is believed that fatty liver is due to the dramatic reduction in circulating IGF1 altering systemic metabolism, due to loss of the insulin-like effects of IGF1 and the loss of IGF1 negative feedback to the pituitary leading to a rise in GH that promotes systemic insulin resistance and WAT lipolysis shifting the flux of fatty acids to the liver. In addition, low IGF1/high GH alters the development of other metabolically relevant tissues, which could indirectly contribute to the liver phenotype observed with congenital loss of hepatic GH signaling. To directly test the actions of GH on adult hepatocyte function, we developed a mouse model of adult-onset, hepatocyte-specific knockdown of the GHR (aHepGHRkd; 12 week-old, GHRfl/fl mice treated with AAV8-TBGp-Cre). aHepGHRkd enhanced hepatic de novo lipogenesis (DNL), rapidly leading to steatosis in males, but not females. In males, enhanced DNL and steatosis was sustained with age and associated with hepatocyte ballooning, inflammation and mild fibrosis. These changes occurred independent of severe systemic insulin resistance and WAT lipolysis, although the aHepGHRkd mice exhibit low IGF1/high GH similar to that of congenital models. To directly test the role of hepatocyte GHR signaling, independent of changes in IGF1, aHepGHRkd mice were treated with a vector expressing rat IGF1 targeted specifically to hepatocytes (AAV8-TBGp-rIGF1). Mice were fed standard chow diet and tissues collected 8m post-AAV. IGF1 replacement elevated plasma IGF1 in aHepGHRkd mice, resulting in a reduction in plasma GH and pituitary expression of Gh, Ghrhr and Ghsr, indicating negative feedback of IGF1 was restored. In male aHepGHRkd mice, IGF1 replacement reduced insulin and whole body lipid utilization and increased WAT, however it did not reduce steatosis or alter hepatic fatty acid composition indicative of DNL and had minimal effects on liver injury markers. RNAseq analysis of liver extracts showed IGF1 replacement also had no major impact on the differentially expressed genes observed after aHepGHRkd. These results demonstrate that steatosis, DNL and liver injury observed in male aHepGHRkd mice are autonomous of IGF1. Despite the fact that hepatic GHR protein levels were not detectable in both female and male aHepGHRkd mice, females maintained moderate levels of IGF1 and were protected from steatosis. The mechanism by which female mice are protected remains to be elucidated, however is consistent with clinical data indicating pre-menopausal women are resistance to NAFLD.

scholarly journals Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men

2020 ◽  
Vol 21 (11) ◽  
pp. 4144 ◽  
Author(s):  
Pia Fahlbusch ◽  
Birgit Knebel ◽  
Tina Hörbelt ◽  
David Monteiro Barbosa ◽  
Aleksandra Nikolic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Energy Metabolism ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Hepatic Insulin Resistance ◽  
Alcoholic Fatty Liver

Fatty liver occurs from simple steatosis with accumulated hepatic lipids and hepatic insulin resistance to severe steatohepatitis, with aggravated lipid accumulation and systemic insulin resistance, but this progression is still poorly understood. Analyses of hepatic gene expression patterns from alb-SREBP-1c mice with moderate, or aP2-SREBP-1c mice with aggravated, hepatic lipid accumulation revealed IGFBP2 as key nodal molecule differing between moderate and aggravated fatty liver. Reduced IGFBP2 expression in aggravated fatty liver was paralleled with promoter hypermethylation, reduced hepatic IGFBP2 secretion and IGFBP2 circulating in plasma. Physiologically, the decrease of IGFBP2 was accompanied with reduced fatty acid oxidation and increased de novo lipogenesis potentially mediated by IGF1 in primary hepatocytes. Furthermore, methyltransferase and sirtuin activities were enhanced. In humans, IGFBP2 serum concentration was lower in obese men with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) compared to non-obese controls, and liver fat reduction by weight-loss intervention correlated with an increase of IGFBP2 serum levels. In conclusion, hepatic IGFBP2 abundance correlates to its circulating level and is related to hepatic energy metabolism and de novo lipogenesis. This designates IGFBP2 as non-invasive biomarker for fatty liver disease progression and might further provide an additional variable for risk prediction for pathogenesis of fatty liver in diabetes subtype clusters.

scholarly journals Raphani Semen (Raphanus sativus L.) Ameliorates Alcoholic Fatty Liver Disease by Regulating De Novo Lipogenesis

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4448
Author(s):  
Woo Yong Park ◽  
Gahee Song ◽  
Joon Hak Noh ◽  
Taegon Kim ◽  
Jae Jin Kim ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Histological Structure ◽  
Fatty Acid Transport ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

In this study, we investigated the pharmacological effect of a water extract of Raphani Semen (RSWE) on alcoholic fatty liver disease (AFLD) using ethanol-induced AFLD mice (the NIAAA model) and palmitic acid (PA)-induced steatosis HepG2 cells. An RSWE supplement improved serum and hepatic triglyceride (TG) levels of AFLD mice, as well as their liver histological structure. To explore the molecular action of RSWE in the improvement of AFLD, we investigated the effect of RSWE on four major pathways for lipid homeostasis in the liver: free fatty acid transport, lipogenesis, lipolysis, and β-oxidation. Importantly, RSWE decreased the mRNA expression of de novo lipogenesis-related genes, such as Srebf1, Cebpa, Pparg, and Lpin1, as well as the protein levels of these factors, in the liver of AFLD mice. That these actions of RSWE affect lipogenesis was confirmed using PA-induced steatosis HepG2 cells. Overall, our findings suggest that RSWE has the potential for improvement of AFLD by inhibiting de novo lipogenesis.

scholarly journals Polyphenols and non-alcoholic fatty liver disease: impact and mechanisms

2015 ◽  
Vol 75 (1) ◽  
pp. 47-60 ◽  
Author(s):  
I. Rodriguez-Ramiro ◽  
D. Vauzour ◽  
A. M. Minihane
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
De Novo ◽  
Regulatory Element ◽  
Whole Body ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
The Impact ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic component of the metabolic syndrome and its prevalence is rapidly increasing due to its strong association with insulin resistance and obesity. At present, given that NAFLD is highly prevalent and therapies are limited, much attention is focused on identifying effective dietary strategies for the prevention and treatment of the disease. Polyphenols are a group of plant bioactive compounds whose regular consumption have been associated with a reduction in the risk of a number of metabolic disorders associated with NAFLD. Here we review the emerging and relatively consistent evidence from cell culture and rodent studies showing that select polyphenols positively modulate a variety of contributors to the NAFLD phenotype, through diverse and complementary mechanisms of action. In particular, the reduction ofde novolipogenesis (via sterol regulatory element-binding protein 1c) and increased fatty acid β-oxidation, presumably involving AMP-activated protein kinase activation, will be discussed. The indirect antioxidant and anti-inflammatory properties of polyphenols which have been reported to contribute to the amelioration of NAFLD will also be addressed. In addition to a direct study of the liver, rodent studies have provided insight into the impact of polyphenols on adipose tissue function and whole body insulin sensitivity, which are likely to in part modulate their impact on NAFLD development. Finally an overview of the limited data from clinical trials will be given along with a discussion of the dose extrapolation from animal studies to human subjects.

scholarly journals USP7 mediates pathological hepatic de novo lipogenesis through promoting stabilization and transcription of ZNF638

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Wenkai Ni ◽  
Shengli Lin ◽  
Saiyan Bian ◽  
Wenjie Zheng ◽  
Lishuai Qu ◽  
...  
Keyword(s):  
Fatty Acid Synthase ◽  
Zinc Finger Protein ◽  
De Novo ◽  
Binding Protein ◽  
Regulatory Element ◽  
Liver Steatosis ◽  
Underlying Mechanism ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Element Binding Protein

Abstract Aberrant de novo lipogenesis (DNL) results in excessive hepatic lipid accumulation and liver steatosis, the causative factors of many liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). However, the underlying mechanism of DNL dysregulation remains largely unknown. Ubiquitination of proteins in hepatocytes has been shown to be widely involved in lipid metabolism of liver. Here, we revealed that Ubiquitin-specific peptidase 7 (USP7), a deubiquitinase (DUB), played key roles in DNL through regulation of zinc finger protein 638 (ZNF638) in hepatocytes. USP7 has been shown not only to interact with and deubiquitylate ZNF638, but also to facilitate the transcription of ZNF638 via the stabilization of cAMP responsive element binding protein (CREB). USP7/ZNF638 axis selectively increased the cleavage of sterol regulatory element binding protein (SREBP1C) through AKT/mTORC1/S6K signaling, and formed USP7/ZNF638/SREBP1C nuclear complex to regulate lipogenesis-associated enzymes, including acetyl-CoA carboxylase (ACACA), fatty acid synthase (FASN), and Stearoyl-CoA desaturase (SCD). In the mice liver steatosis model induced by fructose, USP7 or ZNF638 abrogation significantly ameliorated disease progression. Furthermore, USP7/ZNF638 axis participated in the progression of lipogenesis-associated HCC. Our results have uncovered a novel mechanism of hepatic DNL, which might be beneficial to the development of new therapeutic targets for hepatic lipogenesis-associated diseases.

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