The regulation of food intake is a promising way to combat
obesity. It has been implicated that various
fatty acids exert different effects on food intake and
body weight. However, the underlying mechanism remains poorly understood. The aim of the present study was to investigate the effects of
linoleic acid (LA) and
stearic acid (SA) on
agouti-related protein (AgRP) expression and secretion in immortalized mouse hypothalamic N38 cells and to explore the likely underlying mechanisms. Our results demonstrated that LA inhibited, while SA stimulated AgRP expression and secretion of N38 cells in a dose-dependent manner. In addition, LA suppressed the
protein expression of
toll-like receptor 4 (TLR4), phosphorylation levels of JNK and IKKα/β, suggesting the inhibition of TLR4-dependent
inflammation pathway. However, the above mentioned inhibitory effects of LA were eliminated by TLR4 agonist
lipopolysaccharide (LPS). In contrast, SA promoted TLR4
protein expression and activated TLR4-dependent
inflammation pathway, with elevated ratio of p-JNK/JNK. While TLR4
siRNA reversed the stimulatory effects of SA on AgRP expression and TLR4-dependent
inflammation. Moreover, we found that TLR4 was also involved in LA-enhanced and SA-impaired
leptin/
insulin signal pathways in N38 cells. In conclusion, our findings indicated that LA elicited inhibitory while SA exerted stimulatory effects on AgRP expression and secretion via TLR4-dependent
inflammation and
leptin/
insulin pathways in N38 cells. These data provided a better understanding of the mechanism underlying
fatty acids-regulated food intake and suggested the potential role of long-chain
unsaturated fatty acids such as LA in reducing food intake and treating
obesity.