The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions

Abstract

Manganese (Mn) is an essential element that is involved in the synthesis and activation of many enzymes and in the regulation of the metabolism of glucose and lipids in humans. In addition, Mn is one of the required components for Mn superoxide dismutase (MnSOD) that is mainly responsible for scavenging reactive oxygen species (ROS) in mitochondrial oxidative stress. Both Mn deficiency and intoxication are associated with adverse metabolic and neuropsychiatric effects. Over the past few decades, the prevalence of metabolic diseases, including type 2 diabetes mellitus (T2MD), obesity, insulin resistance, atherosclerosis, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and hepatic steatosis, has increased dramatically. Previous studies have found that ROS generation, oxidative stress, and inflammation are critical for the pathogenesis of metabolic diseases. In addition, deficiency in dietary Mn as well as excessive Mn exposure could increase ROS generation and result in further oxidative stress. However, the relationship between Mn and metabolic diseases is not clear. In this review, we provide insights into the role Mn plays in the prevention and development of metabolic diseases.

Figure 1

Physiological roles of Mn.

Figure 2

The mechanisms of Mn in metabolic diseases via oxidative stress. (a) Mn deficiency will cause a number of detrimental effects, such as impaired growth, poor bone formation and skeletal defects, reduced fertility and birth defects, abnormal glucose tolerance, and altered lipid and carbohydrate metabolism in both animals and humans. Therefore, Mn deficiency might lead to mitochondrial dysfunction or disorder via decreasing MnSOD level and altering lipid and carbohydrate metabolism. (b) Mn overloaded may disrupt normal mitochondrial function by increasing mitochondrial ROS, inhibiting ATP production, and altering membrane permeability; further result in mitochondrial dysfunction or disorder; and finally cause MetS or metabolic diseases. Excessive ROS and oxidative stress would lead to MetS or metabolic diseases directly. If MetS or metabolic diseases happen, it will in turn increase ROS production and oxidative stress and accelerate mitochondrial dysfunction or disorder.