A high-fat diet increases IL-1, IL-6, and TNF-α production by increasing NF-κB and attenuating PPAR-γ expression in bone marrow mesenchymal stem cells.
It is well established that a high-fat diet (HFD) can lead to overweight and ultimately to obesity, as well as promoting low-grade chronic inflammation associated with increased levels of such mediators as TNF-α, IL-1, and IL-6. Bone marrow mesenchymal stem cells (MSCs), which are involved in hematopoietic niches and microenvironments, can be affected by these cytokines, resulting in induction of NF-κB and inhibition of PPAR-γ. Because this phenomenon could ultimately lead to suppression of bone marrow adipogenesis, we set out to investigate the effect of an HFD on the expression of PPAR-γ and NF-κB, as well as the production of IL-1, IL-6, and TNF-α in MSCs. Two-month-old male Wistar rats were fed a HFD diet and evaluated by means of leukograms and myelograms along with blood total cholesterol, triglyceride, and C-reactive protein levels. MSCs were isolated, and PPAR-γ and NF-κB were quantified, as well as IL-1, IL-6, and TNF-α production. Animals that were fed a HFD showed higher levels of blood total cholesterol, triglycerides, and C-reactive protein with leukocytosis and bone marrow hyperplasia. MSCs from HFD animals showed increased production of IL-1, IL-6, and TNF-α and increased NF-κB and reduced PPAR-γ expression. Therefore, ingestion of an HFD induces alterations in MSCs that may influence modulation of hematopoiesis.
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900, São Paulo, São Paulo, Brazil.
Mayara
M
Cortez
Luciana Simão
LS
Carmo
Marcelo Macedo
MM
Rogero
Primavera
P
Borelli
Ricardo Ambrósio
RA
Fock
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D006410:Hematopoiesis; D006965:Hyperplasia; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007964:Leukocytosis; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis*; D047495:PPAR gamma / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D047495:PPAR gamma; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D002784:Cholesterol