How the duration of energy deficit in mice model affects the body composition, bone phenotype, and bone marrow stromal cell differentiation capacity?

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Avilkina, Viktorija | Leterme, Damien | Falgayrac, Guillaume | Marchandise, Pierre | Miellot, Flore | Gauthier, Véronique | Chauveau, Christophe | Ghali Mhenni, Olfa

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International audience. Background/Introduction: Anorexia nervosa is known to induce changes in bone parameters that depend on the duration and seriousness of the disease. Many studies using mouse models showed that bone parameters are altered in response to extended caloric restriction (CR) as described in anorectic patients. Sirtuin Type 1 (Sirt1), a histone deacetylase (HDAC), was shown to have pro-osteoblastic and anti-adipogenic effects by deacetylating transcription factors. We recently demonstrated that a 10-week Separation-Based Anorexia (SBA) protocol, which causes a 18% body weight loss and bone alterations, is associated with a significant decreased Sirt1 expression in Bone Marrow Stromal Cells (BMSCs) from female mice.Purpose: Thus, we hypothesised that this decrease is involved in changing BMSC differentiation capacity and therefore inducing bone alterations.Methods: To test this hypothesis, we compared SBA mice after 10 and 4 weeks of protocol, to determine if alterations of bone, BMSC differentiation and Sirt1 expression levels could be disconnected.Results: Concerning body composition, 4-week and 10-week SBA protocols induced a significant decrease in subcutaneous and visceral adipose tissues as well as a shortened tibia length. Analysis of bone parameters showed that these two SBA protocols led to a reduction in BV/TV and trabecular thickness. However, a significant decrease in cortical thickness is only observed in 10-week protocol. Interestingly, only the 10-week SBA protocol induced a significant and lasting decline in Sirt1 mRNA level, accompanied with an increase in adipogenesis at the expense of osteogenesis.Conclusion(s): In conclusion, our study showed that energy deficit duration is involved in changes in body composition, bone parameters, BMSC differentiation and Sirt1 expression. It also showed that BMSC differentiation and cortical bone phenotype were associated to Sirt1 expression. The prospects are now to determine the molecular mechanisms responsible for decreased Sirt1 expression by epigenetic and RNA sequencing approaches.

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