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.

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 Non-alcoholic fatty liver disease (NAFLD) – epidemic of the XXI century

2018 ◽  
Vol 72 ◽  
pp. 659-670 ◽  
Author(s):  
Dominika Maciejewska ◽  
Ewa Stachowska
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
De Novo ◽  
Serum Insulin ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The term “non-alcoholic fatty liver disease” (NAFLD) was first introduced by Ludwig in 1980. He described NAFLD as a liver disease characterized by lipid accumulation in the hepatocytes of people who do not abuse alcohol (<20g/ethanol/day). NAFLD comprises of a range of disorders, including simple fatty liver without the symptoms of damaged hepatocytes, as well as complex fatty liver with an ongoing inflammation and developing fibrosis. It is estimated that 2-44% of adult Europeans will develop a fatty liver. The pathogenesis and development of NAFLD is a complicated process involving numerous factors, such as: dyslipidemia, insulin resistance, overweight, obesity, mitochondrial dysfunction, oxidative stress, the development of an inflammatory state, the disorders of the metabolism of fat tissue, dysbiosis and genetic factors. Because the mechanism of the illness is based on many factors, the multiple hits hypothesis serves as the new and generally standard approach to this pathological unit. The basis of this theory is the development of insulin resistance, which is one of the main causes of steatosis. The consequence of insulin resistance is an increased glucose level (associated with impaired insulin receptors) and excessive insulin production leading to elevated levels of this hormone in the serum. Insulin resistance causes continuous stimulation of gluconeogenesis and hyperglycemia. On the other hand, hyperinsulinemia stimulates the hepatic synthesis of the de novo lipogenesis and leads to steatosis. NAFLD is also closely connected to the metabolism disorders of fatty acids. The pathomechanism of the illness includes an increased concentration of FFA in blood, an increase in the biosynthesis of fatty acids in the liver, as well as disorders in the process of β-oxidation.

Critical role of NFκB in the pathogenesis of non-alcoholic fatty liver disease: a widespread key regulator

2020 ◽  
Vol 20 ◽  
Author(s):  
Lorenzo Franceschetti ◽  
Francesca Bonomini ◽  
Luigi Fabrizio Rodella ◽  
Rita Rezzani
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
De Novo ◽  
Critical Role ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Inflammatory Reactions ◽  
Alcoholic Fatty Liver Disease

: Non-alcoholic fatty liver disease is a chronic metabolic disorder representing the most common cause of chronic liver disease in western civilization and one of the main causes of cirrhosis with a significant impact on all-cause mortality in the most advanced phases. It is characterized by hepatic fat accumulation in the absence of significant ethanol consumption, virus infection or other specific causes of liver disease. Accumulation of fat in liver tissue occurs as a consequence of the imbalance between overconsumption of high-fat diet and increased de novo lipogenesis and decreased lipid disposal. Novel dietary and pharmacological therapies for the prevention of fatty liver disease and the progression to cirrhosis are an actual field of study but still poorly understood. In this perspective, the current review aims to summarise and clarify the transcription factor NFκB effects, which may exert among non-alcoholic fatty liver diseases and their progression. Through extensive previous research, it has become clear that several signaling pathways are involved: metabolic dysregulation (such as free fatty acids increase, adipokine alteration, insulin resistance), oxidative stress and inflammation contribute together in a “vicious circle” to the pathogenesis of non-alcoholic fatty liver diseases. Within this, NFκB signaling is a primary factor in inflammatory reactions and diseases, with important molecular connections between metabolic, oxidative, immune and inflammation systems.

scholarly journals The Role of the Transsulfuration Pathway in Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 10 (5) ◽  
pp. 1081
Author(s):  
Mikkel Parsberg Werge ◽  
Adrian McCann ◽  
Elisabeth Douglas Galsgaard ◽  
Dorte Holst ◽  
Anne Bugge ◽  
...  
Keyword(s):  
Liver Disease ◽  
Animal Models ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Precise Control ◽  
Transsulfuration Pathway ◽  
Global Population ◽  
Alcoholic Fatty Liver Disease

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and approximately 25% of the global population may have NAFLD. NAFLD is associated with obesity and metabolic syndrome, but its pathophysiology is complex and only partly understood. The transsulfuration pathway (TSP) is a metabolic pathway regulating homocysteine and cysteine metabolism and is vital in controlling sulfur balance in the organism. Precise control of this pathway is critical for maintenance of optimal cellular function. The TSP is closely linked to other pathways such as the folate and methionine cycles, hydrogen sulfide (H2S) and glutathione (GSH) production. Impaired activity of the TSP will cause an increase in homocysteine and a decrease in cysteine levels. Homocysteine will also be increased due to impairment of the folate and methionine cycles. The key enzymes of the TSP, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are highly expressed in the liver and deficient CBS and CSE expression causes hepatic steatosis, inflammation, and fibrosis in animal models. A causative link between the TSP and NAFLD has not been established. However, dysfunctions in the TSP and related pathways, in terms of enzyme expression and the plasma levels of the metabolites (e.g., homocysteine, cystathionine, and cysteine), have been reported in NAFLD and liver cirrhosis in both animal models and humans. Further investigation of the TSP in relation to NAFLD may reveal mechanisms involved in the development and progression of NAFLD.

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