Sake lees extract improves hepatic lipid accumulation in high fat diet-fed mice

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) is increasing worldwide as one of the leading causes of chronic liver disease. Sake lees (SL) are secondary products of sake manufacturing and are considered to have beneficial effects on human health. To investigate these effects, we used high fat diet (HFD)-fed mice treated with or without the SL extract.MethodMice were the HFD ad libitum for 8 weeks and were administered 500 μL of distilled water with or without the SL extract (350 mg/mL) by a feeding needle daily for the last 4 weeks. Food intake, body weight, and liver weight were measured. Triacylglycerol content and the mRNA and protein expression levels of various lipid and glucose metabolism-related genes were determined in liver tissues. The levels of triglyceride, free fatty acids, glucose, insulin, and liver cell damage markers were determined in serum. Fatty acid-induced lipid accumulation in HepG2 cells was assessed in the presence or absence of the SL extract.ResultsMice fed a HFD and treated with the SL extract demonstrated a significant reduction in hepatic lipid accumulation and mRNA and protein levels of peroxidome proliferator-activated receptor γ (PPARγ), PPARα, CD36, and phosphoenolpyruvate carboxykinase 1 in the liver, while the SL extract did not affect body weight and food intake. Moreover, insulin resistance and hepatic inflammation in HFD-fed mice improved after administration of the SL extract. In HepG2 cells, the SL extract suppressed fatty acid-induced intracellular lipid accumulation.ConclusionsThese findings suggest that treatment with the SL extract could potentially reduce the risk of NAFLD development, and that the SL extract may be clinically useful for the treatment of NAFLD.

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns

“…Collectively, hepatic lipid accumulation can cause hepatic insulin resistance through multiple mechanisms (Konstantynowicz et al, 2011). Therefore, it is widely accepted that suppression of hepatic lipid accumulation is a promising approach for the therapy of hepatic insulin resistance (Konstantynowicz et al, 2011; Mohamed and Jornayvaz, 2013; Kubo et al, 2017).…”

“…Free fatty acids are by-products of fat metabolism in adipose tissues. The cause–effect relationship between hepatic free fatty acid accumulation and hepatic insulin resistance has been well described (Liu et al, 2015; Kubo et al, 2017).…”

“…Therefore, as one of the important fuel sources, moderate levels of fatty acids in liver and muscle tissues are essential for cellular activities. However, excessive fatty acid accumulation in liver and muscle tissues is a pathological condition (Kubo et al, 2017).…”

Effect of Sake Lees on the Inhibition of Lipid Accumulation in Adipocytes

“…Animal studies have revealed that sake lees have functional properties, such as inhibiting cholesterol increase, lowering blood pressure, and inhibiting liver damage in mice. Moreover, clinical studies have reported improved environmental conditions in human intestines [9,10]. However, the mechanisms of action of sake lees and the roles of their specific components are unknown.…”

Effects of Dietary Ethanol Extracts from Sake Rice and Sake Lees on Intestinal Impairment in Mice

“…Sake lees sake-kasu, sake cake is a byproduct of sake and is used as a bed for pickling kasu-duke , a material of soup and drink kasu-jiru and amazake , and a source for Japanese spirits and vinegar kasutori-shochu and kasu-zu . Sake lees has been reported to improve hepatic lipid accumulation 13 and has been shown to contain GlcCer with a fungi-specific sphingoid base 14 .…”