Dichotomous effects of VEGF-A on adipose tissue dysfunction

Obese fat pads are frequently undervascularized and hypoxic, leading to increased fibrosis, inflammation, and ultimately insulin resistance. We hypothesized that VEGF-A-induced stimulation of angiogenesis enables sustained and sufficient oxygen and nutrient exchange during fat mass expansion, thereby improving adipose tissue function. Using a doxycycline (Dox)-inducible adipocyte-specific VEGF-A overexpression model, we demonstrate that the local up-regulation of VEGF-A in adipocytes improves vascularization and causes a "browning" of white adipose tissue (AT), with massive up-regulation of UCP1 and PGC1 alpha. This is associated with an increase in energy expenditure and resistance to high fat diet-mediated metabolic insults. Similarly, inhibition of VEGF-A-induced activation of VEGFR2 during the early phase of high fat diet-induced weight gain, causes aggravated systemic insulin resistance. However, the same VEGF-A-VEGFR2 blockade in ob/ob mice leads to a reduced body-weight gain, an improvement in insulin sensitivity, a decrease in inflammatory factors, and increased incidence of adipocyte death. The consequences of modulation of angiogenic activity are therefore context dependent. Proangiogenic activity during adipose tissue expansion is beneficial, associated with potent protective effects on metabolism, whereas antiangiogenic action in the context of preexisting adipose tissue dysfunction leads to improvements in metabolism, an effect likely mediated by the ablation of dysfunctional proinflammatory adipocytes.

Effects of visual and auditory stimuli in a choice reaction time task

The effect produced by a warning stimulus(i) (WS) in reaction time (RT) tasks is commonly attributed to a facilitation of sensorimotor mechanisms by alertness. Recently, evidence was presented that this effect is also related to a proactive inhibition of motor control mechanisms. This inhibition would hinder responding to the WS instead of the target stimulus (TS). Some studies have shown that auditory WS produce a stronger facilitatory effect than visual WS. The present study investigated whether the former WS also produces a stronger inhibitory effect than the latter WS. In one session, the RTs to a visual target in two groups of volunteers were evaluated. In a second session, subjects reacted to the visual target both with (50% of the trials) and without (50% of the trials) a WS. During trials, when subjects received a WS, one group received a visual WS and the other group was presented with an auditory WS. In the first session, the mean RTs of the two groups did not differ significantly. In the second session, the mean RT of the two groups in the presence of the WS was shorter than in their absence. The mean RT in the absence of the auditory WS was significantly longer than the mean RT in the absence of the visual WS. Mean RTs did not differ significantly between the present conditions of the visual and auditory WS. The longer RTs of the auditory WS group as opposed to the visual WS group in the WS-absent trials suggest that auditory WS exert a stronger inhibitory influence on responsivity than visual WS.