RESUMEN
Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed the obese mouse phenotype. Moreover, obese human subjects showed lower expression of Par-4 relative to lean subjects, and in longitudinal studies, low baseline Par-4 levels denoted an increased risk of developing obesity later in life. These findings indicate that Par-4 suppresses p53 and its target c3 to regulate obesity.
RESUMEN
Over the past decade, the use of probiotics to modify the gut microbiome has become a public spotlight in reducing the severity of a number of chronic diseases such as autoimmune disease, diabetes, cancer and cardiovascular disease. Recently, the gut microbiome has been shown to play an important role in regulating bone mass. Therefore, targeting the gut microbiome may be a potential alternative avenue for those with osteopenia or osteoporosis. In this mini-review, we take the opportunity to delve into how the different components of the gut work together and how the gut-related diseases impact on bone health.