Metabolic Changes of Hepatocytes in NAFLD

Abstract

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by systemic metabolic disorders such as hyperglycemia, insulin resistance, and obesity. The relationship between NAFLD and systemic metabolic disorders has been well reviewed before, however, the metabolic changes that occur in hepatocyte itself have not been discussed. In NAFLD, many metabolic pathways have undergone significant changes in hepatocyte, such as enhanced glycolysis, gluconeogenesis, lactate production, tricarboxylic acid (TCA) cycle, and decreased ketone body production, mitochondrial respiration, and adenosine triphosphate (ATP) synthesis, which play a role in compensating or exacerbating disease progression, and there is close and complex interaction existed between these metabolic pathways. Among them, some metabolic pathways can be the potential therapeutic targets for NAFLD. A detailed summary of the metabolic characteristics of hepatocytes in the context of NAFLD helps us better understand the pathogenesis and outcomes of the disease.

Hyperpolarized carbon 13 MRI in liver diseases: Recent advances and future opportunities

“…Abnormal glucose and lipid metabolism also often occurs in NAFLD patients. 17 In addition, metabolic reprogramming in hepatocellular carcinoma (HCC), especially the increased lactate production, 18 can be identified by HP 13 C MRI. Compared to current imaging methods, HP 13 C MRI provides unique metabolic information about pathway-specific alterations without using ionizing radiation.…”

“…For example, the activity of ALT is usually elevated in patients with liver injury, which can lead to the increase of [1‐ 13 C]alanine. Abnormal glucose and lipid metabolism also often occurs in NAFLD patients 17 . In addition, metabolic reprogramming in hepatocellular carcinoma (HCC), especially the increased lactate production, 18 can be identified by HP 13 C MRI.…”

Adaptation of Oxidative Phosphorylation Machinery Compensates for Hepatic Lipotoxicity in Early Stages of MAFLD

“…The role of the various metabolic pathways, including glycolytic pathways in NAFLD and MAFLD, was recently reviewed [ 37 , 38 , 39 ]. Transcriptional analyses and meta-analyses thereof have been performed in humans with various stages of NAFLD in comparison to healthy controls or obese patients.…”

Novel insights into non-alcoholic fatty liver disease and dementia: insulin resistance, hyperammonemia, gut dysbiosis, vascular impairment, and inflammation

“…NAFLD is an important disease related to the development of dementia. It is associated with insulin resistance, hyperammonemia, gut dysbiosis, impaired cerebrovascular function, and inflammatory responses, leading to dementia disturbances, including insulin resistance and elevated serum free fatty acid and serum pyruvate concentrations [25]. Circulation of these metabolites can affect the brain [26].…”

“…Liver function abnormalities negatively affect energy metabolism because the liver plays an key role in metabolism, and abnormal energy metabolism contributes to abnormal energy storage [ 24 ]. A variety of metabolic processes, such as glycolysis, lipogenesis, and gluconeogenesis are impaired, which ultimately leads to systemic metabolic disturbances, including insulin resistance and elevated serum free fatty acid and serum pyruvate concentrations [ 25 ]. Circulation of these metabolites can affect the brain [ 26 ].…”