The Transcriptomic Landscape of Age-Induced Changes in Human Visceral Fat and the Predicted Omentum-Liver Connectome in Males
Diogo de Moraes,
Felippe Mousovich-Neto,
Sarah Santiloni Cury,
Jakeline Oliveira,
Jeferson dos Santos Souza,
Paula Paccielli Freire,
Maeli Dal-Pai-Silva,
Marcelo Alves da Silva Mori,
Geysson Javier Fernandez,
Robson Francisco Carvalho
Affiliations
Diogo de Moraes
Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Sao Paulo State University, UNESP, Botucatu 18618-689, SP, Brazil
Felippe Mousovich-Neto
Department of Biochemistry and Tissue Biology, University of Campinas, Monteiro Lobato St., 255, Campinas 13083-862, SP, Brazil
Sarah Santiloni Cury
Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Sao Paulo State University, UNESP, Botucatu 18618-689, SP, Brazil
Jakeline Oliveira
Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Sao Paulo State University, UNESP, Botucatu 18618-689, SP, Brazil
Jeferson dos Santos Souza
Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Sao Paulo State University, UNESP, Botucatu 18618-689, SP, Brazil
Paula Paccielli Freire
Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Sao Paulo State University, UNESP, Botucatu 18618-689, SP, Brazil
Maeli Dal-Pai-Silva
Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Sao Paulo State University, UNESP, Botucatu 18618-689, SP, Brazil
Marcelo Alves da Silva Mori
Department of Biochemistry and Tissue Biology, University of Campinas, Monteiro Lobato St., 255, Campinas 13083-862, SP, Brazil
Geysson Javier Fernandez
Grupo Biologia y Control de Enfermedades Infeciosas (BCEI), Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia (UdeA), Medellín 050010, Colombia
Robson Francisco Carvalho
Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Sao Paulo State University, UNESP, Botucatu 18618-689, SP, Brazil
Aging causes alterations in body composition. Specifically, visceral fat mass increases with age and is associated with age-related diseases. The pathogenic potential of visceral fat accumulation has been associated with its anatomical location and metabolic activity. Visceral fat may control systemic metabolism by secreting molecules that act in distal tissues, mainly the liver, through the portal vein. Currently, little is known about age-related changes in visceral fat in humans. Aiming to identify molecular and cellular changes occurring with aging in the visceral fat of humans, we analyzed publicly available transcriptomic data of 355 omentum samples from the Genotype-Tissue Expression portal (GTEx) of 20–79-year-old males and females. We identified the functional enrichment of genes associated with aging, inferred age-related changes in visceral fat cellularity by deconvolution analysis, profiled the senescence-associated secretory phenotype of visceral adipose tissue, and predicted the connectivity of the age-induced visceral fat secretome with the liver. We demonstrate that age induces alterations in visceral fat cellularity, synchronous to changes in metabolic pathways and a shift toward a pro-inflammatory secretory phenotype. Furthermore, our approach identified candidates such as ADIPOQ-ADIPOR1/ADIPOR2, FCN2-LPR1, and TF-TFR2 to mediate visceral fat-liver crosstalk in the context of aging. These findings cast light on how alterations in visceral fat with aging contribute to liver dysfunction and age-related disease etiology.
