The spectrum of adipose tissue diseases ranges from
obesity to
lipodystrophy, and is accompanied by
insulin resistance syndrome, which promotes the occurrence of
type 2 diabetes,
dyslipidemia and cardiovascular complications.
Lipodystrophy refers to a group of
rare diseases characterized by the generalized or partial absence of adipose tissue, and occurs with or without
hypertrophy of adipose tissue in other sites. They are classified as being familial or acquired, and generalized or partial. The genetically determined partial forms usually occur as
Dunnigan syndrome, which is a type of
laminopathy that can also manifest as muscle, cardiac, neuropathic or progeroid involvement. Gene mutations encoding for
PPAR-gamma, Akt2, CIDEC,
perilipin and the ZMPSTE 24
enzyme are much more rare. The genetically determined generalized forms are also very rare and are linked to mutations of seipin AGPAT2, FBN1, which is accompanied by
Marfan syndrome, or of BANF1, which is characterized by a progeroid syndrome without
insulin resistance and with early bone complications. Glycosylation disorders are sometimes involved. Some genetically determined forms have recently been found to be due to autoinflammatory syndromes linked to a
proteasome anomaly (PSMB8). They result in a
lipodystrophy syndrome that occurs secondarily with
fever,
dermatosis and
panniculitis. Then there are forms that are considered to be acquired. They may be iatrogenic (
protease inhibitors in HIV patients, glucocorticosteroids,
insulin,
graft-versus-host disease, etc.), related to an
immune system disease (sequelae of
dermatopolymyositis, autoimmune polyendocrine syndromes, particularly associated with
type 1 diabetes, Barraquer-Simons and Lawrence syndromes), which are promoted by anomalies of the
complement system. Finally,
lipomatosis is currently classified as a painful form (
adiposis dolorosa or
Dercum's disease) or benign symmetric multiple form, also known as
Launois-Bensaude syndrome or
Madelung's disease, which are sometimes related to
mitochondrial DNA mutations, but are usually promoted by alcohol. In addition to the medical management of
metabolic syndrome and the sometimes surgical treatment of
lipodystrophy, recombinant
leptin provides hope for genetically determined
lipodystrophy syndromes, whereas modifications in antiretroviral treatment and
tesamorelin, a GHRH analog, is effective in the
metabolic syndrome of HIV patients. Other therapeutic options will undoubtedly be developed, dependent on pathophysiological advances, which today tend to classify genetically determined
lipodystrophy as being related to
laminopathy or to lipid droplet disorders.