Abstract
Metabolic illnesses such as non-alcoholic fatty liver disease (NAFLD) are in constant increase worldwide. Highly consumed long chain fatty acids (LCFA) are among the most obesogenic and steatogenic nutrients. Hepatic steatosis is associated with several complications such as insulin resistance. Growing evidence points to medium chain fatty acids (MCFA), more efficiently oxidized than LCFA, as a promising dietary alternative against NAFLD. However, reports on the hepatic effects of MCFA are sometimes conflicting. In this study we exposed HepG2 cells, a human hepatocellular model, to 0.25 mM of hexanoic (C6), or octanoic (C8), and decanoic (C10) acids separately or in a C8 + C10 equimolar mix reflecting commercially available MCFA-rich oils. We found that C6, a poorly studied MCFA, as well as C8 and C10 did not provoke the deleterious lipid anabolism runaway typically induced by LCFA palmitate. MCFA tended, instead, to promote a balanced metabolic profile and were generally non-cytotoxic. Accordingly, mitochondrial integrity was mostly preserved following MCFA treatment. However, treatments with C8 induced a mitochondrial membrane potential decrease, suggesting prolonged exposure to this lipid could be problematic. Finally, MCFA treatments maintained optimal insulin sensitivity and even fostered basal and insulin-dependent phosphorylation of the Akt-mTOR pathway. Overall, MCFA could constitute an effective nutritional tool to manage liver steatosis and hepatic insulin resistance.
Highlights
IntroductionNon-alcoholic fatty liver disease (NAFLD) is the most widespread chronic liver illness with a prevalence reaching 20–30% within the general population and 80–90% among obese patients [1,2]
Non-alcoholic fatty liver disease (NAFLD) is the most widespread chronic liver illness with a prevalence reaching 20–30% within the general population and 80–90% among obese patients [1,2].In addition to consequences directly related to liver dysfunction, NAFLD is closely associated with several pathologies including metabolic syndrome, obesity, cardiovascular disease, insulin resistance, and type 2 diabetes [1,3]
This study was designed to compare the effects of medium chain fatty acids (MCFA) with palmitate, a representative long chain fatty acids (LCFA), on lipid metabolism and insulin sensitivity in a hepatocellular model
Summary
Non-alcoholic fatty liver disease (NAFLD) is the most widespread chronic liver illness with a prevalence reaching 20–30% within the general population and 80–90% among obese patients [1,2]. In addition to consequences directly related to liver dysfunction, NAFLD is closely associated with several pathologies including metabolic syndrome, obesity, cardiovascular disease, insulin resistance, and type 2 diabetes [1,3]. The excessive accumulation of triglycerides (TG) within the liver, is the major hallmark of NAFLD. Liver steatosis is characterized by the intracellular accumulation of lipid droplets (LD) in more than 5% of cytoplasmic space [3,4,5]. The pathogenesis of NAFLD is largely due to lipotoxicity [6,7]. Triglyceride accumulation in the core of Molecules 2018, 23, 2315; doi:10.3390/molecules23092315 www.mdpi.com/journal/molecules
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