HIV type-1 transgene expression in mice alters adipose tissue and adipokine levels: towards a rodent model of HIV type-1 lipodystrophy.
BACKGROUND
Lipodystrophy in HIV type-1 (HIV-1)-infected patients is the consequence of effects originating from antiretroviral treatment and HIV-1 infection. We have studied adipose tissues and circulating parameters in mice bearing the HIV-1 transgene as a model to provide insight into the role of HIV-1-infection-related events in fat alterations.


METHODS
Heterozygous transgenic mice expressing a 7.7 kb HIV-1 construct (Tg26+/-) were used. Cytokine and adipokine levels were quantified using multiplex procedures. Gene expression and mitochondrial DNA abundance in visceral and subcutaneous white adipose tissues and in brown fat were determined using quantitative real-time PCR.


RESULTS
The amount of visceral, but not subcutaneous, adipose depot was lower in Tg26+/- mice. Serum proinflammatory cytokine levels were increased in Tg26+/- mice, whereas adiponectin and leptin levels were reduced. Gene expression of monocyte chemoattractant protein-1 was induced in visceral and subcutaneous fat, whereas tumour necrosis factor-α and interleukin-6 were induced in visceral and subcutaneous white adipose tissues, respectively. Adiponectin and leptin gene expression was repressed in all white fat depots, in concert with reduced expression of peroxisome proliferator-activated receptor γ, a master controller of adipogenesis. In brown fat, a coordinate induction in the expression of thermogenesis marker genes was observed.


CONCLUSIONS
HIV-1 transgene expression in mice causes changes in adipose tissue reminiscent of those in patients with HIV-1 lipodystrophy, particularly early pretreatment changes. These data support a role for HIV-1-infection-related events in eliciting adipose tissue dysfunction. The Tg26+/- mouse appears as a promising model to assess the effects of HIV-1 infection on adipose tissue and for determining the effects of antiretroviral drugs on an HIV-1-infected background.
Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
Joan
J
Villarroya
Julieta
J
Diaz-Delfin
Deborah
D
Hyink
Pere
P
Domingo
Marta
M
Giralt
Paul E
PE
Klotman
Francesc
F
Villarroya
D050156:Adipogenesis; D054392:Adipokines / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D039682:HIV-Associated Lipodystrophy Syndrome / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D020738:Leptin; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D050151:Subcutaneous Fat / Q000737:chemistry / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000737:chemistry / Q000378:metabolism
D054392:Adipokines; D052242:Adiponectin; D018932:Chemokine CCL2; D015850:Interleukin-6; D020738:Leptin