HIV infection drives proinflammatory adipocyte differentiation in an in vitro model and reveals a new inflammatory pathway
IntroductionAdipose tissue regulates metabolic homeostasis and serves as a reservoir for mesenchymal stem cells (MSCs), which differentiate into osteoblasts and adipocytes, balancing bone and lipid metabolism. Bone loss and fat accumulation are common in individuals living with HIV, prompting us to...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| author | Rosa Nicole Freiberger Cynthia Alicia Marcela López Franco Agustin Sviercz Patricio Jarmoluk María Belén Palma María Belén Palma Marcela Nilda García Jorge Quarleri M. Victoria Delpino |
| author_facet | Rosa Nicole Freiberger Cynthia Alicia Marcela López Franco Agustin Sviercz Patricio Jarmoluk María Belén Palma María Belén Palma Marcela Nilda García Jorge Quarleri M. Victoria Delpino |
| author_sort | Rosa Nicole Freiberger |
| collection | DOAJ |
| description | IntroductionAdipose tissue regulates metabolic homeostasis and serves as a reservoir for mesenchymal stem cells (MSCs), which differentiate into osteoblasts and adipocytes, balancing bone and lipid metabolism. Bone loss and fat accumulation are common in individuals living with HIV, prompting us to investigate how R5- and X4-tropic HIV modulates adipocyte differentiation and tissue homeostasis using an in vitro model of MSC-derived adipogenesis.MethodsThe study used an in vitro model of MSCs to examine how R5- and X4-tropic HIV strains affect adipocyte differentiation and function. Researchers assessed adipogenesis by analyzing lipid droplet formation, expression of adipogenic transcription factors (C/EBPα, C/EBPβ, PPAR-γ), lipogenic/lipolytic enzymes, SREBPs, cytokine secretion, and the effects of CXCR4 and CCR5 with specific inhibitors.ResultsHIV exposure influences adipogenesis, increasing lipid droplet size in a tropism dependent manner and upregulating key adipogenic factors such as C/EBPα, C/ EBPβ, and PPAR-γ. This process involves the regulation of lipogenic and lipolytic enzymes, lipid droplet-lysosome interactions, and potential lipid droplet mitochondria cross-talk to fuel lipid accumulation. Additionally, HIV modulates sterol regulatory element-binding proteins (SREBPs), which control fatty acid, triacylglycerol, and cholesterol synthesis. Notably, SREBP2 downregulation correlates with increased type I interferons (IFNa2, IFNb1), linking lipid metabolism to immune responses in HIV infection. HIV-infected adipocytes also exhibit an increased leptin/adiponectin ratio and enhanced IL-1b and IL-6 secretion, contributing to the inflammatory state observed in people with HIV. CXCR4 plays a key role in adipocyte differentiation, as its inhibition with AMD3100 reduces adipocyte number, size, and lipid droplet accumulation under X4-tropic HIV exposure. In contrast, CCR5 does not appear to be significantly involved in adipose tissue homeostasis under R5-tropic HIV exposure.DiscussionThese findings, derived from an in vitro model, suggest that HIV alters MSC differentiation into adipocytes, impacting adipose tissue homeostasis and function. |
| format | Article |
| id | doaj-art-7535ab7bbdcd40c19d187a6f9ebdeb72 |
| institution | DOAJ |
| issn | 2235-2988 |
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| publishDate | 2025-07-01 |
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| spelling | doaj-art-7535ab7bbdcd40c19d187a6f9ebdeb722025-08-20T02:40:04ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-07-011510.3389/fcimb.2025.16279631627963HIV infection drives proinflammatory adipocyte differentiation in an in vitro model and reveals a new inflammatory pathwayRosa Nicole Freiberger0Cynthia Alicia Marcela López1Franco Agustin Sviercz2Patricio Jarmoluk3María Belén Palma4María Belén Palma5Marcela Nilda García6Jorge Quarleri7M. Victoria Delpino8Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, ArgentinaCátedra de Citología, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Buenos Aires, ArgentinaInstituto de Neurociencias (INEU-CONICET), Laboratorio de Investigación Aplicada en Neurociencias (LIAN), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Escobar, Buenos Aires, ArgentinaCátedra de Citología, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Consejo de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, ArgentinaIntroductionAdipose tissue regulates metabolic homeostasis and serves as a reservoir for mesenchymal stem cells (MSCs), which differentiate into osteoblasts and adipocytes, balancing bone and lipid metabolism. Bone loss and fat accumulation are common in individuals living with HIV, prompting us to investigate how R5- and X4-tropic HIV modulates adipocyte differentiation and tissue homeostasis using an in vitro model of MSC-derived adipogenesis.MethodsThe study used an in vitro model of MSCs to examine how R5- and X4-tropic HIV strains affect adipocyte differentiation and function. Researchers assessed adipogenesis by analyzing lipid droplet formation, expression of adipogenic transcription factors (C/EBPα, C/EBPβ, PPAR-γ), lipogenic/lipolytic enzymes, SREBPs, cytokine secretion, and the effects of CXCR4 and CCR5 with specific inhibitors.ResultsHIV exposure influences adipogenesis, increasing lipid droplet size in a tropism dependent manner and upregulating key adipogenic factors such as C/EBPα, C/ EBPβ, and PPAR-γ. This process involves the regulation of lipogenic and lipolytic enzymes, lipid droplet-lysosome interactions, and potential lipid droplet mitochondria cross-talk to fuel lipid accumulation. Additionally, HIV modulates sterol regulatory element-binding proteins (SREBPs), which control fatty acid, triacylglycerol, and cholesterol synthesis. Notably, SREBP2 downregulation correlates with increased type I interferons (IFNa2, IFNb1), linking lipid metabolism to immune responses in HIV infection. HIV-infected adipocytes also exhibit an increased leptin/adiponectin ratio and enhanced IL-1b and IL-6 secretion, contributing to the inflammatory state observed in people with HIV. CXCR4 plays a key role in adipocyte differentiation, as its inhibition with AMD3100 reduces adipocyte number, size, and lipid droplet accumulation under X4-tropic HIV exposure. In contrast, CCR5 does not appear to be significantly involved in adipose tissue homeostasis under R5-tropic HIV exposure.DiscussionThese findings, derived from an in vitro model, suggest that HIV alters MSC differentiation into adipocytes, impacting adipose tissue homeostasis and function.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1627963/fullHIVadipocyteMSCslipid droplets (LD)adipogenesis |
| spellingShingle | Rosa Nicole Freiberger Cynthia Alicia Marcela López Franco Agustin Sviercz Patricio Jarmoluk María Belén Palma María Belén Palma Marcela Nilda García Jorge Quarleri M. Victoria Delpino HIV infection drives proinflammatory adipocyte differentiation in an in vitro model and reveals a new inflammatory pathway Frontiers in Cellular and Infection Microbiology HIV adipocyte MSCs lipid droplets (LD) adipogenesis |
| title | HIV infection drives proinflammatory adipocyte differentiation in an in vitro model and reveals a new inflammatory pathway |
| title_full | HIV infection drives proinflammatory adipocyte differentiation in an in vitro model and reveals a new inflammatory pathway |
| title_fullStr | HIV infection drives proinflammatory adipocyte differentiation in an in vitro model and reveals a new inflammatory pathway |
| title_full_unstemmed | HIV infection drives proinflammatory adipocyte differentiation in an in vitro model and reveals a new inflammatory pathway |
| title_short | HIV infection drives proinflammatory adipocyte differentiation in an in vitro model and reveals a new inflammatory pathway |
| title_sort | hiv infection drives proinflammatory adipocyte differentiation in an in vitro model and reveals a new inflammatory pathway |
| topic | HIV adipocyte MSCs lipid droplets (LD) adipogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1627963/full |
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