The recent studies discussed in this review show that sPLA2s can influence metabolic diseases such as Type 2 diabetes and obesity, at least partially through alterations in lipid production and mobilization (Figure 1); and while controversy exists regarding whether elevated lipids directly cause insulin resistance, pre-clinical and clinical data indicate an association between elevated lipids and lipoproteins with insulin resistance (74–77). The gene discussed is PLA2G2D; the disease is obesity due to melanocortin 4 receptor deficiency.