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Galanin is colocalized extensively with norepinephrine in brain. Although this suggests possible activity-dependent neurotransmitter interactions, the functional significance of such colocalization remains elusive. Previously, we showed that enhancing stress-activation of the noradrenergic system by yohimbine pretreatment released galanin in central amygdala, attenuating the anxiety-like behavioral response to stress on the elevated plus-maze. The present study was conducted to determine, in this context, whether galanin was indeed coreleased from noradrenergic terminals, or instead from another galanin afferent or local stress-responsive galanin neurons in the amygdala. In experiment 1, galanin-mediated anxiolytic effects on the plus-maze following yohimbine + stress were unaltered by lesioning the noradrenergic innervation of central amygdala. In experiment 2, combining immunohistochemistry and in situ hybridization, galanin neurons specifically activated by yohimbine + stress treatment were found only in the locus coeruleus and intraamygdalar bed nucleus of the stria terminalis, adjacent to central amygdala. In experiment 3, retrograde tracing combined with in situ hybridization revealed few if any galanin cells projecting to central amygdala in locus coeruleus or nucleus tractus solitarius, sources of noradrenergic innervation. Indeed, few retrogradely-labeled galanin neurons were observed anywhere in the brain, including a small number in the intraamygdalar bed nucleus. Together, these results suggest that stress following yohimbine may have induced galanin release from an afferent to central amygdala originating in the bed nucleus, or from local neurons in the intraamygdalar bed nucleus, but that anxiolytic effects exerted by galanin in this context of elevated noradrenergic activity were not the result of corelease from noradrenergic terminals innervating central amygdala.

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Obesity is associated with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Obesity and metabolic abnormalities resulting in low-grade inflammation can increase the risk of developing NASH and HCC. NASH, a risk factor for HCC, is characterized by increased inflammation, lipid accumulation, and liver injury. Obesogenic proteins modulate signaling pathways that induce physiological changes including lipogenesis, ROS, and inflammation. Silibinin, a polyphenol in milk thistle seed, has been shown to have anti-inflammatory properties. Studies have yet to determine whether silibinin can be used to dissect the obesity-cancer link to delay progression of liver cancer. Using an in vitro model, sera from obese (OB), overweight (OW), or normal weight (NW) males (based on BMI) were used to determine the efficacy of silibinin to reduce the pro-tumorigenic properties of obesity. HepG2 cells were exposed to OB, OW, NW ± silibinin and tested for growth, ROS, lipogenesis, MMP-9, invasion and protein expression. Silibinin suppressed obesity-induced growth, ROS, lipogenesis, MMP-9, and cell invasion. These physiological changes corresponded with decreased FASN, IL-6, IL-1B, and phosphorylated Erk. We describe the differential effect of sera from OB, OW, and NW males on characteristics relevant for liver cancer and the potential use of silibinin to mitigate these effects.

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