AI Article Synopsis

  • Skatole (3-methylindole) is a natural compound found in plants and human intestines, recognized for its potential health benefits and as a marker for certain diseases.
  • Hepatic lipotoxicity, linked to excess saturated free fatty acids, leads to damage in liver cells and is a crucial factor in the development of metabolic diseases like nonalcoholic fatty liver disease (NAFLD).
  • The study found that skatole protects liver cells from damage caused by lipotoxicity, improves insulin resistance, reduces fat accumulation, and lowers oxidative stress effects in hyperlipidemic conditions.

Article Abstract

Skatole (3-methylindole, 3MI) is a natural-origin compound derived from plants, insects, and microbial metabolites in human intestines. Skatole has an anti-lipid peroxidation effect and is a biomarker for several diseases. However, its effect on hepatocyte lipid metabolism and lipotoxicity has not been elucidated. Hepatic lipotoxicity is induced by excess saturated free fatty acids in hyperlipidemia, which directly damages the hepatocytes. Lipotoxicity is involved in several metabolic diseases and hepatocytes, particularly affecting nonalcoholic fatty liver disease (NAFLD) progression. NAFLD is caused by the accumulation of fat by excessive free fatty acids (FFAs) in the blood and is accompanied by hepatic damage, such as endoplasmic reticulum (ER) stress, abnormal glucose and insulin metabolism, oxidative stress, and lipoapoptosis with lipid accumulation. Hepatic lipotoxicity causes multiple hepatic damages in NAFLD and has a directly effect on the progression from NAFLD to nonalcoholic steatohepatitis (NASH). This study confirmed that the natural compound skatole improves various damages to hepatocytes caused by lipotoxicity in hyperlipidemic conditions. To induce lipotoxicity, we exposed HepG2, SNU-449, and Huh7 cells to palmitic acid, a saturated fatty acid, and confirmed the protective effect of skatole. Skatole inhibited fat accumulation in the hepatocytes, reduced ER and oxidative stress, and recovered insulin resistance and glucose uptake. Importantly, skatole reduced lipoapoptosis by regulating caspase activity. In conclusion, skatole ameliorated multiple types of hepatocyte damage induced by lipotoxicity in the presence of excess free fatty acids.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052055PMC
http://dx.doi.org/10.3390/nu15061490DOI Listing

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