Abstract
The liver is primarily responsible for energy homeostasis and the regulation of lipid, carbohydrate and protein metabolism. Lipid metabolism consists of distributing lipids to peripheral tissues or ensuring their return to the liver to be reprocessed. Additionally, cellular metabolism is regulated by several molecules in different signaling pathways. Lipid homeostasis in the liver is mainly regulated by AKT, AMPK, SREBP, PPAR, and JNK. The PI3K/AKT/mTOR signaling pathway results in the biosynthesis of macromolecules and regulates lipogenesis and the expression of lipogenic genes. AMPK is an energy sensor that regulates metabolism and is activated when stored ATP is depleted, and it is responsible for the suppression of several key lipogenic factors in the liver related to cholesterol and fatty acid synthesis. SREBPs control lipogenic gene expression and cholesterol metabolism and act in the nutritional regulation of fatty acids and triglycerides. The continued activation of SREBPs is associated with cellular stress, inflammation and ultimately steatosis. PPARs are intrinsically important regulators of lipid metabolism. These genes are essential to various metabolic processes, especially lipid and glucose homeostasis, and can play a role in cell differentiation. JNK signaling is related to insulin resistance and its activation results in decreased mitochondrial activity and fat accumulation. Therefore, the study of cell signaling pathways related to lipid metabolism and liver function may help to identify abnormalities and develop strategies to manage and regulate metabolic disorders and resulting complications.
Highlights
The liver consists largely of hepatocytes, the major scaffold for lipoprotein synthesis, but it contains many other cell types (Aizawa, Seki, Nagano, & Abe, 2015; La Rosa Rodriguez & Kersten, 2017)
The central cell signaling pathways related to lipid metabolism include AKT, AMPK, SREBP, peroxisome proliferator-activated receptors (PPARs) and Jun N-terminal kinase (JNK)
Regarding lipid metabolism, phosphorylated AMPK can improve high-fat-diet-induced non-alcoholic steatohepatitis (NASH) through the suppression of several key lipogenic factors in the liver related to cholesterol and fatty acid synthesis, such as sterol regulatory element-binding protein (SREBP-1), which results in reduced triglyceride synthesis, HMG-CoAR levels, cholesterol synthesis, and ACC enzyme activation, which in turn decreases malonyl-CoA levels and reduces free fatty acids and VLDL synthesis (Musso et al, 2016; Su et al, 2017)
Summary
The liver consists largely of hepatocytes, the major scaffold for lipoprotein synthesis, but it contains many other cell types (Aizawa, Seki, Nagano, & Abe, 2015; La Rosa Rodriguez & Kersten, 2017). The diseases or metabolic disorders related to lipid processing have a large public health impact because of both the increasing population affected worldwide and the potential of these disorders to advance to chronic complications that lead to poor quality of life, in which is associated with increased global expenditures directly connected to those health issues as well as high morbidity and mortality rates (Trogdon et al, 2015). Some of the most important pathological conditions associated with lipid metabolic disorders include type 2 diabetes mellitus, obstructive sleep apnea, coronary artery disease, non-alcoholic steatohepatitis (NASH) and some types of cancer (Tang, 2016). The central cell signaling pathways related to lipid metabolism include AKT, AMPK, SREBP, PPAR and JNK. Understanding lipid metabolism and liver function as well as the main signaling pathways connected to these phenomena, is crucial to identify abnormalities and develop strategies to manage and regulate metabolic disorders and metabolic disorder-associated complications
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