One of the earliest insights into the potential role of the peripheral GC-C system in regulating adipocyte function emerged from transcriptomic analysis of rats fed a high-fat diet (HFD), which revealed high expression of guanylin and GC-C in mesenteric fat in lean rats that resisted dietary obesity, versus those that developed obesity (186). This evidence concerns the gene GUCY2C and obesity due to melanocortin 4 receptor deficiency.