I thank Wilkinson et al. (1) for their helpful comments on our article (2). As they summarized well in their review article (3), many adipokines including leptin, resistin, and Angptl4/Fiaf are expressed in the brain, although their biological functions remain to be established. Supporting our study, Wilkinson and colleagues (4,5) previously demonstrated the expression of Agnptl4/Fiaf in the mouse hypothalamus and hypothalamic neuronal cells.

In our study (2), hypothalamic Angpt4/Fiaf protein levels were actively regulated by nutrient availability and physiological appetite regulators such as leptin and insulin. By contrast, Agnptl4/Fiaf mRNA levels were not much changed by 24-h fast in the previous study by Wilkinson et al. (4). Similar results were found in our own study (2) and are presented in supplementary data. These findings suggest a possibility that the altered metabolic condition may influence hypothalamic Agnptl4/Fiaf expression through post-transcriptional mechanisms. Indeed, we have shown that the ratio of full-length and truncated Angptl4/Fiaf was increased by administration of leptin and insulin, indicating that leptin and insulin may inhibit degradation of full-length Angptl4/Fiaf into biologically less effective fragments.

Previous studies by Wilkinson and colleagues (6,7) showed that traumatic and ischemic brain injuries elevated Angpt4/Fiaf mRNA levels in the cortex, hippocampus, thalamus, and pituitary glands. These findings lead us to speculate that hypothalamic Angpt4/Fiaf might be upregulated in brain injury models and result in anorexia and weight loss. Therefore, it will be worthwhile to test a role for hypothalamic Angpt4/Fiaf in disease-related body weight regulation.

No potential conflicts of interest relevant to this article were reported.

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