Nobiletin is a naturally occurring phenolic compound (polymethoxylated flavone) that is found in orange, lemon, and other citrus fruits.
It has been proposed to exhibit several health benefits, with previous studies demonstrating that it reduced hyperglycaemia, glucose tolerance and insulin resistance in obese diabetic mice.
However, the long-term effects of low-dose nobiletin on metabolic disorders in high-fat diet-induced obese mice was still unclear, said the researchers from Chung-Ang University College of Medicine, Kyungpook National University and Pukyong National University in Korea, and Chubu University in Japan.
Writing in the journal Molecular Nutrition and Food Research, they stated mice were fed a high-fat diet with or without nobiletin for 16 weeks.
They reported that nobiletin significantly decreased not only pro-inflammatory genes expression in adipose tissue but also pro-inflammatory cytokine levels in plasma.
Nobiletin supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin.
It did not, however, affect adipose tissue weight.
“In the current study, we demonstrated that long-term supplementation with low-dose nobiletin protected against these metabolic disturbances in high-fat diet-induced obese mice, although nobiletin had no significant effect on adiposity,” they wrote.
“Nobiletin did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity.”
Decreased collagen deposition
The researchers also examined whether nobiletin could protect the liver from high-fat diet induced injury.
“Supplementation with nobiletin significantly down-regulated TNF-α mRNA expression in the livers of high-fat diet-fed mice. Moreover, levels of plasma AST and ALT, indicators of hepatocellular injury, were significantly lower in nobiletin-supplemented mice compared to those in control mice.
“Trichrome staining of the liver also revealed nobiletin supplementation decreased collagen deposition (arrows) compared to the control mice.”
The study concluded that long-term supplementation with low-dose nobiletin could exert beneficial effects on high-fat diet induced metabolic disturbances such as non-alcoholic fatty liver disease and dyslipidaemia.
“These results could be linked to the activation of hepatic fatty acid oxidation, anti-inflammatory action, and improved insulin resistance, independent of the effect of nobiletin on adiposity,” they stated.
Source: Molecular Nutrition and Food Research
“Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity”
Authors: Young-Je Kim, et al.