Dataset Information

High-fat diet disturbs lipid raft/TGF-? signaling-mediated maintenance of hematopoietic stem cells in mouse bone marrow.

ABSTRACT: Despite recent in vivo data demonstrating that high-fat diet (HFD)-induced obesity leads to major perturbations in murine hematopoietic stem cells (HSC), the direct role of a HFD is not yet completely understood. Here, we investigate the direct impact of a short-term HFD on HSC and hematopoiesis in C57BL/6J mice compared with standard diet-fed mice. We detect a loss of half of the most primitive HSC in the bone marrow (BM) cells of HFD-fed mice, which exhibit lower hematopoietic reconstitution potential after transplantation. Impaired maintenance of HSC is due to reduced dormancy after HFD feeding. We discover that a HFD disrupts the TGF-? receptor within lipid rafts, associated to impaired Smad2/3-dependent TGF-? signaling, as the main molecular mechanism of action. Finally, injecting HFD-fed mice with recombinant TGF-?1 avoids the loss of HSC and alteration of the BM's ability to recover, underscoring the fact that a HFD affects TGF-? signaling on HSC.

SUBMITTER: Hermetet F

PROVIDER: S-EPMC6355776 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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High-fat diet disturbs lipid raft/TGF-β signaling-mediated maintenance of hematopoietic stem cells in mouse bone marrow.

Hermetet François F Buffière Anne A Aznague Aziza A Pais de Barros Jean-Paul JP Bastie Jean-Noël JN Delva Laurent L Quéré Ronan R

Nature communications 20190131 1

Despite recent in vivo data demonstrating that high-fat diet (HFD)-induced obesity leads to major perturbations in murine hematopoietic stem cells (HSC), the direct role of a HFD is not yet completely understood. Here, we investigate the direct impact of a short-term HFD on HSC and hematopoiesis in C57BL/6J mice compared with standard diet-fed mice. We detect a loss of half of the most primitive HSC in the bone marrow (BM) cells of HFD-fed mice, which exhibit lower hematopoietic reconstitution p ...[more]

PMID: 30705272

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Project description:ObjectiveDiet structure has changed greatly over the last few decades, and high-calorie diets have become an integral part of people's daily diet, as well as the important cause of obesity in society. Several organ systems, including the skeletal system, are seriously affected by high-fat-diets (HFD) in the world. There is, however, still a lack of knowledge about the effects of HFD on bone regeneration and the possible mechanisms involved. In this study, the difference in bone regeneration between rats under HFD and low-fat-diets (LFD) was evaluated by monitoring the process of bone regeneration in distraction osteogenesis (DO) model animals, as well as the possible mechanisms.MethodsA total of 40 Sprague Dawley (SD) rats (5 weeks old) were randomly divided into HFD group (n=20) and LFD group (n=20). Except for feeding methods, there were no differences between the two groups in terms of treatment conditions. All animals received the DO surgery eight weeks after starting to feed. After a delay of 5 days (latency phase), the active lengthening phase was performed for 10 days (0.25 mm/12 h), and the consolidation phase followed for 42 days. An observational study of bone included radioscopy (once a week), micro-computed tomography (CT), general morphology, biomechanics, histomorphometry, and immunohistochemistry.ResultThe results showed that HFD group had a higher body weight than LFD group after 8, 14, and 16 weeks of feeding. Furthermore, at the final observation, there were statistically significant differences between LFD group and HFD group in terms of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Additionally, observations on bone regeneration showed a slower regeneration and a lower biomechanical strength in HFD group than LFD group, based on radiography, micro-CT, general morphology, biomechanics, histomorphometry, and immunohistochemistry.ConclusionIn this study, HFD resulted in elevated blood lipids, increased adipose differentiation at the bone marrow level, and delayed bone regeneration. The pieces of evidence are beneficial to better understand the association between diet and bone regeneration and to adjust the diet optimally for fracture patients.

Dataset Information

High-fat diet disturbs lipid raft/TGF-? signaling-mediated maintenance of hematopoietic stem cells in mouse bone marrow.

Publications

High-fat diet disturbs lipid raft/TGF-β signaling-mediated maintenance of hematopoietic stem cells in mouse bone marrow.

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