We think that further investigations are warranted in the following areas: (1) the molecular mechanisms by which VA regulates the transcription of critical metabolic genes in different organs and tissues, such as Gck, Pck1, and Srebp-1c; (2) the interplay between VA and other hormones in the regulation of metabolic homeostasis; (3) the roles of VA in the regulation of macronutrient metabolism in various disease states, especially obesity, type 2 diabetes, and other metabolic diseases. The gene discussed is PCK1; the disease is obesity due to melanocortin 4 receptor deficiency.