In this review, we focus on four key metabolic GPCRs—GPR40, GPR120, GLP-1R, and β-adrenergic receptors (ADRB1, ADRB2, and ADRB3)—with respect to their roles in metabolic physiology and significance in obesity and related metabolic diseases (Figure 1). This evidence concerns the gene FFAR4 and obesity due to melanocortin 4 receptor deficiency.