Mitochondria are small sub-cellular organelles often referred to as the powerhouse of cells as they produce more than 95% of the energy required by cells. Mitochondria are essential to our survival and are responsible for many other essential metabolic processes including lipid and carbohydrate metabolism. Mitochondria are unique as they contain their own genome that codes for 13 proteins involved in energy production. The mitochondrial genome is regulated by a family of RNA-binding proteins known as pentatricopeptide repeat (PPR) proteins. Defects in the regulation of mitochondrial gene expression can arise due to mutations and environmental factors such as a high caloric diet and sedentary lifestyle. Such defects lead to mitochondrial dysfunction which can result in diminished energy production and consequently metabolic disease, including insulin resistance, obesity and type 2 diabetes. Little is known about how defects in mitochondrial gene expression can lead to changes in energy metabolism observed in metabolic disease. Here we investigated the link between a specific mitochondrial RNA-binding protein and the development and onset of metabolic disease via the characterization of a unique mouse model. We show that the mitochondrial RNA-binding protein is essential for the regulation of gene expression. Reduction of this protein leads to mitochondrial dysfunction and consequently the development of an age-induced metabolic syndrome. We further show the molecular mechanisms that potentiate different cellular pathways which provides insight into the onset and development of disease in this mouse model. We conclude that reduction of the mitochondrial RNA-binding protein is a predisposing factor for the development of a metabolic syndrome and this novel mouse model provides a useful tool for the study of metabolic disease.