The
flavonoid luteolin has various pharmacological activities. However, few studies exist on the in vivo mechanism underlying the actions of
luteolin in hepatic steatosis and
obesity. The aim of the current study was to elucidate the action of
luteolin on
obesity and its comorbidity by analyzing its transcriptional and metabolic responses, in particular the
luteolin-mediated cross-talk between liver and adipose tissue in diet-induced obese mice. C57BL/6J mice were fed a normal, high-fat, and high-fat + 0.005% (weight for weight)
luteolin diet for 16 weeks. In high fat-fed mice,
luteolin improved hepatic steatosis by suppressing hepatic lipogenesis and
lipid absorption. In adipose tissue,
luteolin increased PPARĪ³
protein expression to attenuate hepatic lipotoxicity, which may be linked to the improvement in circulating
fatty acid (FA) levels by enhancing FA uptake genes and lipogenic genes and
proteins in adipose tissue. Interestingly,
luteolin also upregulated the expression of genes controlling lipolysis and the
tricarboxylic acid (TCA) cycle prior to lipid droplet formation, thereby reducing adiposity. Moreover,
luteolin improved hepatic
insulin sensitivity by suppressing SREBP1 expression that modulates Irs2 expression through its negative feedback and gluconeogenesis.
Luteolin ameliorates the deleterious effects of diet-induced
obesity and its comorbidity via the interplay between liver and adipose tissue.