Sara Guerra1,2, Gabriele Mocciaro1, Amalia Gastaldelli1,2. 1. Institute of Clinical Physiology (IFC), National Research Council (CNR), Pisa, Italy. 2. Sant'Anna School of Advanced Studies, Pisa, Italy.
Abstract
BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) is now 25% in the general population but increases to more than 55% in subjects with obesity and/or type 2 diabetes. Simple steatosis (NAFL) can develop into more severe forms, that is non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma leading to death. METHODS: In this narrative review, we have discussed the current knowledge in the pathophysiology of fatty liver disease, including both metabolic and non-metabolic factors, insulin resistance, mitochondrial function, as well as the markers of liver damage, giving attention to the alterations in lipid metabolism and production of lipotoxic lipids. RESULTS: Insulin resistance, particularly in the adipose tissue, is the main driver of NAFLD due to the excess release of fatty acids. Lipidome analyses have shown that several lipids, including DAGs and ceramides, and especially if they contain saturated lipids, act as bioactive compounds, toxic to the cells. Lipids can also affect mitochondrial function. Not only lipids, but also amino acid metabolism is impaired in NAFL/NASH, and some amino acids, as branched-chain and aromatic amino acids, glutamate, serine and glycine, have been linked to impaired metabolism, insulin resistance and severity of NAFLD and serine is a precursor of ceramides. CONCLUSIONS: The measurement of lipotoxic species and adipose tissue dysfunction can help to identify individuals at risk of progression to NASH.
BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) is now 25% in the general population but increases to more than 55% in subjects with obesity and/or type 2 diabetes. Simple steatosis (NAFL) can develop into more severe forms, that is non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma leading to death. METHODS: In this narrative review, we have discussed the current knowledge in the pathophysiology of fatty liver disease, including both metabolic and non-metabolic factors, insulin resistance, mitochondrial function, as well as the markers of liver damage, giving attention to the alterations in lipid metabolism and production of lipotoxic lipids. RESULTS: Insulin resistance, particularly in the adipose tissue, is the main driver of NAFLD due to the excess release of fatty acids. Lipidome analyses have shown that several lipids, including DAGs and ceramides, and especially if they contain saturated lipids, act as bioactive compounds, toxic to the cells. Lipids can also affect mitochondrial function. Not only lipids, but also amino acid metabolism is impaired in NAFL/NASH, and some amino acids, as branched-chain and aromatic amino acids, glutamate, serine and glycine, have been linked to impaired metabolism, insulin resistance and severity of NAFLD and serine is a precursor of ceramides. CONCLUSIONS: The measurement of lipotoxic species and adipose tissue dysfunction can help to identify individuals at risk of progression to NASH.
Authors: Sonia M Najjar; Raziyeh Abdolahipour; Hilda E Ghadieh; Marziyeh Salehi Jahromi; John A Najjar; Basil A M Abuamreh; Sobia Zaidi; Sivarajan Kumarasamy; Harrison T Muturi Journal: Biomedicines Date: 2022-08-05
Authors: Gabriele Mocciaro; Simona D'Amore; Benjamin Jenkins; Richard Kay; Antonio Murgia; Luis Vicente Herrera-Marcos; Stefanie Neun; Alice P Sowton; Zoe Hall; Susana Alejandra Palma-Duran; Giuseppe Palasciano; Frank Reimann; Andrew Murray; Patrizia Suppressa; Carlo Sabbà; Antonio Moschetta; Albert Koulman; Julian L Griffin; Michele Vacca Journal: Int J Mol Sci Date: 2022-06-17 Impact factor: 6.208