scholarly journals Modulation of hepatic lipid metabolism by olive oil and its phenols in nonalcoholic fatty liver disease

IUBMB Life ◽  
2015 ◽  
Vol 67 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Paola Priore ◽  
Alessandro Cavallo ◽  
Antonio Gnoni ◽  
Fabrizio Damiano ◽  
Gabriele V. Gnoni ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Olive Oil ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Hepatic Lipid Metabolism ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid

scholarly journals Nonalcoholic Fatty Liver Disease: Pathogenesis and Therapeutics from a Mitochondria-Centric Perspective

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Aaron M. Gusdon ◽  
Ke-xiu Song ◽  
Shen Qu
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathways ◽  
Fatty Liver Disease ◽  
Beta Oxidation ◽  
Hepatic Lipid Metabolism ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of disorders characterized by the accumulation of triglycerides within the liver. The global prevalence of NAFLD has been increasing as the obesity epidemic shows no sign of relenting. Mitochondria play a central role in hepatic lipid metabolism and also are affected by upstream signaling pathways involved in hepatic metabolism. This review will focus on the role of mitochondria in the pathophysiology of NAFLD and touch on some of the therapeutic approaches targeting mitochondria as well as metabolically important signaling pathways. Mitochondria are able to adapt to lipid accumulation in hepatocytes by increasing rates of beta-oxidation; however increased substrate delivery to the mitochondrial electron transport chain (ETC) leads to increased reactive oxygen species (ROS) production and eventually ETC dysfunction. Decreased ETC function combined with increased rates of fatty acid beta-oxidation leads to the accumulation of incomplete products of beta-oxidation, which combined with increased levels of ROS contribute to insulin resistance. Several related signaling pathways, nuclear receptors, and transcription factors also regulate hepatic lipid metabolism, many of which are redox sensitive and regulated by ROS.

scholarly journals Roles of IκB kinases and TANK-binding kinase 1 in hepatic lipid metabolism and nonalcoholic fatty liver disease

2021 ◽  
Author(s):  
Jin Young Huh ◽  
Alan R. Saltiel
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Hepatic Inflammation ◽  
Hepatic Lipid Metabolism ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Iκb Kinase

AbstractNonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is strongly associated with obesity-related ectopic fat accumulation in the liver. Hepatic lipid accumulation encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Given that dysregulated hepatic lipid metabolism may be an onset factor in NAFLD, understanding how hepatic lipid metabolism is modulated in healthy subjects and which steps are dysregulated in NAFLD subjects is crucial to identify effective therapeutic targets. Additionally, hepatic inflammation is involved in chronic hepatocyte damage during NAFLD progression. As a key immune signaling hub that mediates NF-κB activation, the IκB kinase (IKK) complex, including IKKα, IKKβ, and IKKγ (NEMO), has been studied as a crucial regulator of the hepatic inflammatory response and hepatocyte survival. Notably, TANK-binding kinase 1 (TBK1), an IKK-related kinase, has recently been revealed as a potential link between hepatic inflammation and energy metabolism. Here, we review (1) the biochemical steps of hepatic lipid metabolism; (2) dysregulated lipid metabolism in obesity and NAFLD; and (3) the roles of IKKs and TBK1 in obesity and NAFLD.

scholarly journals Excessive early-life cholesterol exposure may have later-life consequences for nonalcoholic fatty liver disease

2020 ◽  
pp. 1-8
Author(s):  
Jerad H. Dumolt ◽  
Mulchand S. Patel ◽  
Todd C. Rideout
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
In Utero ◽  
Regulatory Function ◽  
Hepatic Lipid Metabolism ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid

Abstract The in utero and immediate postnatal environments are recognized as critical windows of developmental plasticity where offspring are highly susceptible to changes in the maternal metabolic milieu. Maternal hypercholesterolemia (MHC) is a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during pregnancy which can program metabolic dysfunction in offspring, including dysregulation of hepatic lipid metabolism. Although there is currently no established reference range MHC, a loosely defined cutoff point for total cholesterol >280 mg/dL in the third trimester has been suggested. There are several unanswered questions regarding this condition particularly with regard to how the timing of cholesterol exposure influences hepatic lipid dysfunction and the mechanisms through which these adaptations manifest in adulthood. Gestational hypercholesterolemia increased fetal hepatic lipid concentrations and altered lipid regulatory mRNA and protein content. These early changes in hepatic lipid metabolism are evident in the postweaning environment and persist into adulthood. Further, changes to hepatic epigenetic signatures including microRNA (miR) and DNA methylation are observed in utero, at weaning, and are evident in adult offspring. In conclusion, early exposure to cholesterol during critical developmental periods can predispose offspring to the early development of nonalcoholic fatty liver disease (NAFLD) which is characterized by altered regulatory function beginning in utero and persisting throughout the life cycle.

scholarly journals Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
James W. Perfield ◽  
Laura C. Ortinau ◽  
R. Taylor Pickering ◽  
Meghan L. Ruebel ◽  
Grace M. Meers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
De Novo ◽  
Hepatic Lipid Metabolism ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid

Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-week-old leptin-deficient Ob/Ob mice, a commonly studied model of obesity and hepatic steatosis. Obese Ob/Ob mice had increased fasting glucose, insulin, and calculated HOMA-IR as compared with lean wild-type (WT) mice. Ob/Ob mice also had greater liver weights, hepatic triglyceride (TG) content, and markers ofde novolipogenesis, including increased hepatic gene expression and protein content of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1), as well as elevated gene expression of PPARγand SREBP-1c compared with WT mice. While hepatic mRNA levels for PGC-1α, PPARα, and TFAM were elevated in Ob/Ob mice, measures of mitochondrial function (β-HAD activity and complete (to CO2) and total mitochondrial palmitate oxidation) and mitochondrial OXPHOS protein subunits I, III, and V content were significantly reduced compared with WT animals. In summary, reduced hepatic mitochondrial content and function and an upregulation inde novolipogenesis contribute to obesity-associated NAFLD in the leptin-deficient Ob/Ob mouse.

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