Efeito do tratamento com restrição calórica na saúde óssea de camundongos obesos alimentados com dieta rica em gordura

Obesity involves excessive secretion of pro-inflammatory adipokines by adipocytes and macrophages due to increased adiposity. This triggers events that negatively affect glycemic and cardiovascular parameters, as well as bone metabolism. Caloric restriction (CR) is a strategy widely used as a treatment for obesity, since caloric deficit is one of the key factors for weight loss. However, the effects of caloric restriction on bone health are complex and present contradictory aspects. The aim of this study was to evaluate the effect of caloric restriction as a dietary treatment on bone health in mice with obesity induced by a high-fat diet (HF). For this purpose, male C57BL/6 mice were divided into: (i) mice fed a Labina® diet (control) and (ii) mice fed a HF diet - 45% of the total calories of the diet. Upon reaching 40 grams, some animals from the HF group were directed to the third group: (iii) mice fed a HF diet, followed by dietary intervention through CR. This intervention included replacing the HF diet with the Labina® diet, and they were subjected to this protocol for a period of 35 days. At the end of the intervention, a glucose tolerance test was performed. The animals were euthanized and adipose tissue, femur and tibia were collected. Histology, micro-computed tomography (MicroCT), serum measurement of bone/metabolic markers and gene expression by real-time PCR were performed. The results showed that the HF diet induced an increase in the adiposity index and adipocyte area, associated with metabolic changes, such as increased fasting serum glucose and worsening oral glucose tolerance. In bone microarchitecture, an increase in the percentage of bone volume (BV/TV) and an increase in the number of trabeculae (T.Sp) were observed, associated with changes in histology, showing a lower number of osteoblasts and osteoclasts. This effect does not seem beneficial due to the adverse consequences on metabolic health and the increase in adiposity induced by the HF diet. In contrast, CR has shown to be a valid treatment strategy for obesity, completely reversing the increase in adiposity and changes in glycemic metabolism induced by the HF diet. In the bone context, CR showed an increased RANKL/OPG ratio, with an increase in osteoblasts and osteoclasts. In bone microarchitecture, CR induced a return to baseline parameters, with a reduction in bone mineral density (BMD), BV/TV and T.Sp, suggesting a reduction proportional to weight loss. Therefore, treatment with caloric restriction appears to reverse the metabolic and bone changes resulting from the consumption of the HF diet. However, it is still crucial to further investigate this CR-induced bone reversal to determine its real impact on bone health, despite its benefits, especially in individuals with bone alterations resulting from obesity.

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