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Dietary ω-3 Fatty Acid Supplementation Improves Murine Sickle Cell Bone Disease and Reprograms Adipogenesis
Maria Teresa Valenti1, Alessandro Mattè1, Enrica Federti1
1Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, 37128 Verona, Italy.
Insights
Omega-3 fatty acids (fish oil) show promise in treating sickle cell bone disease (SBD). This dietary intervention improves bone health and reduces inflammation in mouse models of sickle cell disease (SCD).
Area of Science:
- Biomedical Science
- Nutritional Science
- Hematology
Background:
- Sickle cell disease (SCD) causes chronic hemolytic anemia and organ damage.
- Sickle cell bone disease (SBD) is a prevalent complication leading to disability, pain, and fractures.
Purpose of the Study:
- To evaluate the effects of omega-3 (fish oil-based, FD) versus omega-6 (soybean oil-based, SD) diets on murine sickle cell bone disease (SBD).
- To investigate the impact of these diets on bone metabolism and adipogenesis in sickle cell disease (SCD) models.
Main Methods:
- Murine models of sickle cell disease (SCD) were exposed to recurrent hypoxia/reoxygenation (rec H/R) to simulate SBD.
- Dietary supplementation with omega-3 (FD) or omega-6 (SD) was administered.
- Osteoblastogenesis, osteoclast activity, inflammation, and adipogenesis were assessed.
Main Results:
- In rec H/R SCD mice, the omega-3 enriched diet (FD) improved osteoblastogenesis and osteogenic activity by downregulating osteoclast activity via miR205 modulation.
- FD reduced both systemic and local inflammation in the rec H/R SCD mouse model.
- FD reduced and reprogramed adipogenesis from white to brown adipose tissue (BAT) in bone compartments, evidenced by increased uncoupling protein 1 (UCP1) and miR455 expression.
Conclusions:
- Omega-3 fatty acid supplementation demonstrates a beneficial effect on the pathogenesis of sickle cell bone disease (SBD).
- FD's mechanism involves enhancing osteogenesis, reducing inflammation, and promoting brown adipogenesis in bone.
- Omega-3 fatty acid dietary supplementation is a potential complementary therapeutic strategy for individuals with sickle cell disease (SCD).
Abstract:
Sickle cell disease (SCD) is a genetic disorder of hemoglobin, leading to chronic hemolytic anemia and multiple organ damage. Among chronic organ complications, sickle cell bone disease (SBD) has a very high prevalence, resulting in long-term disability, chronic pain and fractures. Here, we evaluated the effects of ω-3 (fish oil-based, FD)-enriched diet vs. ω-6 (soybean oil-based, SD)- supplementation on murine SBD. We exposed SCD mice to recurrent hypoxia/reoxygenation (rec H/R), a consolidated model for SBD. In rec H/R SS mice, FD improves osteoblastogenesis/osteogenic activity by downregulating osteoclast activity via miR205 down-modulation and reduces both systemic and local inflammation. We also evaluated adipogenesis in both AA and SS mice fed with either SD or FD and exposed to rec H/R. FD reduced and reprogramed adipogenesis from white to brown adipocyte tissue (BAT) in bone compartments. This was supported by increased expression of uncoupling protein 1(UCP1), a BAT marker, and up-regulation of miR455, which promotes browning of white adipose tissue. Our findings provide new insights on the mechanism of action of ω-3 fatty acid supplementation on the pathogenesis of SBD and strengthen the rationale for ω-3 fatty acid dietary supplementation in SCD as a complementary therapeutic intervention.
