title: Ultrastructural features of highly active antiretroviral therapy-associated partial lipodystrophy.
abstract: Chronic treatment with highly active antiretroviral therapy (HAART) results in a novel variety of partial lipodystrophy, combining lipoatrophic and hypertrophic areas. We have previously reported the histopathological features of this disease and have also shown that adipocyte apoptosis is involved in its origin. With the aim of further elucidating the mechanisms underlying this peculiar disorder, we performed an ultrastructural study of the adipocytes of ten HIV-1-infected patients treated with HAART for 20-42 months. In all ten cases, two main sets of ultrastructural changes were identified. Some adipocytes showed disruption of cell membranes, fragmented cytoplasmic rims, irregular cell outlines, and eventually fat droplets laying free in the connective tissue, with a histiocytic reaction around them. In addition, many adipocytes showed variable compartmentalization of fat droplets with decrease in cell size and abundant, mitochondria-rich cytoplasm. Often, a dual "white and brown" fat appearance was observed with a large unilocular vacuole surrounded by a rim of multilocular cytoplasm containing smaller isometric fat droplets and numerous mitochondria. These findings suggest that HAART-associated partial lipodystrophy is probably the result of a remodeling process of fat cells involving variable combinations of apoptosis, defective lipogenesis, and increased metabolic activity in different adipose areas of the body.
authors.affiliation: Department of Pathology, Hospital del Mar-IMAS-IMIM, Universitat Pompeu Fabra, Passeig Maritim 25-29, 08003-Barcelona, Spain. Jlloreta@imas.imim.es
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Ramón M
authors.initials: RM
authors.lastname: Pujol
authors.forename: Juan A
authors.initials: JA
authors.lastname: Arroyo
authors.forename: Núria
authors.initials: N
authors.lastname: Baixeras
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.forename: Montserrat
authors.initials: M
authors.lastname: Gilaberte
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sambeat
authors.forename: Sergi
authors.initials: S
authors.lastname: Serrano
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D017667:Adipocytes / Q000187:drug effects* / Q000648:ultrastructure*; D000328:Adult; D000368:Aged; D000886:Anthropometry; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001823:Body Composition; D005260:Female; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged