A murine model of Hhip haploinsufficiency which closely mimics the impact of genetic variants identified by genome-wide association studies on the gene expression of HHIP in the lung demonstrates increased susceptibility towards the development of emphysema upon exposure to chronic cigarette smoke7; using this model, we explored both baseline differences in metabolism as well as differences induced by exposure to a significant environmental challenge (i.e., chronic cigarette smoke exposure). Here, HHIP is linked to pulmonary emphysema.