CREB1 and obesity due to melanocortin 4 receptor deficiency: In this regard, in a long-term obesity-induced cardiac remodeling model, reduced GRK2 dosage in hemizygous GRK2+/− mice preserves the activation of the PKA/CREB and AMPK pathways downstream of different cardiac GPCR, maintains the expression of key cardioprotective metabolic enzymes and mitochondrial proteins, and thus safeguards these animals from obesity-induced cardiomyocyte hypertrophy, fibrosis, and steatosis (Lucas et al., 2016).