<p>Adipose tissue is a complex organ deputed to energy storage (white adipose tissue), energy production (brown adipose tissue), organ mechanical protection and hormone and cytokine release. The main feature of adipose tissue is probably its plasticity, which is due to the ability of adipocytes to shift from one phenotype to another in processes known as browning or whitening, as well as to increase or decrease its own mass by activating hypertrophy or lipolysis. What happens in lipodystrophies is the progressive loss of such plasticity and the onset of a pathogenetic condition leading to progressive and irreversible fat loss. Such fat loss may occur throughout the body or may spare some depots, as occurs in partial lipodystrophies. However, the mechanisms behind adipose tissue dysfunction are still elusive. Our recent data show that aberrant differentiation of brown adipocytes towards the white lineage underlies the accumulation of neck adipose tissue in familial partial lipodystrophy of the Dunnigan type and the mechanism is associated with recruitment of the mineralocorticoid receptor in the nucleus of brown preadipocytes, which thus tend to aberrantly differentiate towards the white lineage. These findings are consistent with binding of the mineralocorticoid receptor to lamin A, the nuclear envelope protein mutated in type 2 familial partial lipodystrophy and suggest that mineralocorticoid receptor antagonism may prove useful in patient treatment. However, we suggest that the central issue to be addressed in the study of lipodystrophies is the uncoupling of adipose tissue remodelling from environmental conditions, including hormone, nutritional, mechanical and cold stimuli. Such knowledge might provide therapeutic tools able to rescue adipose tissue depots lost in lipodystrophies.</p>