Site-specific differences in the action of NRTI drugs on adipose tissue incubated in vitro with lymphoid cells, and their interaction with dietary lipids.
Existing theories of the origin of HIV-related adipose tissue redistribution syndrome cannot adequately explain simultaneous hypertrophy of certain depots and atrophy of others, or its occasional occurrence in untreated HIV infection. These experiments explore the hypothesis that hypertrophy of lymphoid tissue-containing adipose depots arises from drug-induced disruption to local interactions between perinodal adipocytes and activated lymphoid cells. Guinea pigs were fed on plain or lipid-supplemented (10% suet, sunflower or fish oil) chow ad libitum or restricted, and the popliteal lymph nodes were activated by repeated injection of lipopolysaccharide. Explants of perinodal and other samples from popliteal, mesentery, omentum and nodeless perirenal and epididymal depots were incubated with lymphoid cells and zidovudine, didanosine, lamivudine or stavudine at physiological concentrations (0.1-1 microg/ml) or interleukin-10 and interleukin-6, and basal and maximum lipolysis was measured. All drugs increased lipolysis from perinodal adipocytes, especially mesenteric, though less than exogenous cytokines. Effects on adipocytes from non-perinodal sites and nodeless depots were minimal. The sunflower-oil diet enhanced, and the fish-oil and restricted diets reduced, these effects. We conclude that these NRTI antiretroviral drugs modulate the local interactions between perinodal adipocytes and activated lymphoid cells. Local interactions, and hence the selective hypertrophy of node-containing adipose depots, may be curtailed by dietary manipulation.
Mattacks
Christine A
CA
Department of Biological Sciences, The Open University, Milton Keynes MK7 6AA, UK.
Sadler
Dawn
D
Pond
Caroline M
CM
D017667:Adipocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D016753:Interleukin-10 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
D019380:Anti-HIV Agents; D004041:Dietary Fats; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018894:Reverse Transcriptase Inhibitors; D016753:Interleukin-10