It has also been reported that HFD alone does not induce PH per se but can be amodifying factor resulting in an increase in the severity of hypoxia-induced PHand the penetrance of PH in BMPR2 mutant mice.7,40 This gives some support tothe hypothesis that obesity may act as a ‘second hit’ in some individuals andlead to the development of PAH. The gene discussed is BMPR2; the disease is obesity due to melanocortin 4 receptor deficiency.