Persistent Organic Pollutants released from decomposed adipose tissue affect mitochondrial enzyme function in the brain and eyes other than the liver.

Persistent organic pollutants (POPs) are toxic chemicals that can accumulate in the human body, and particularly in adipose tissue. POPs can induce metabolic diseases via mitochondrial dysfunction and can also cause cancer, obesity, and cardiovascular and neurodegenerative diseases. Although the effects of POPs were studied by evaluating mitochondrial function, which is fundamental in investigating the etiologies of various metabolic diseases, the physiological impact of POPs released by the decomposition of fat in adipose tissue is barely understood. Therefore, to investigate the mitochondrial dysfunction caused by POPs released from adipose tissue to other organs, zebrafish were exposed to POPs and placed into four groups: control (C), obesity control (OC), obesity control with POPs (OP), and POP exposure with obesity and caloric restriction (OPR). Next, the activities of the mitochondrial respiratory complexes and the levels of ATP production, reactive oxygen species/reactive nitrogen species (ROS/RNS), and antioxidants, such as glutathione and superoxide dismutase, were measured in the brain, eyes, and liver, as these are the major organs most susceptible to metabolic diseases. POPs released from adipose tissue showed a stronger effect than the direct effects of obesity and POPs on mitochondrial enzyme activity in the brain and eye. Released POPs increased mitochondrial complex I activity and decreased mitochondrial complex II activity compared with normal, obesity, and POP-treated conditions in the brain and eyes. However, the mitochondrial complexes' activities in the liver were affected more by obesity and POPs. In the liver, the mitochondrial enzyme activities of the OPR group seemed to recover to the control level, but it was slightly lowered in the OC and OP groups. Independently, the ROS/RNS and antioxidant levels were not affected by obesity, POPs, or the released POPs in the brain, eye, and liver. The results indicate that POPs stored in adipose tissue and released during fat decomposition did not affect oxidative stress but could affect mitochondrial respiratory enzymes in organ dependent manner. This study is meaningful in that it provides experimental evidence that stored POPs affect specific organs for prolonged periods and can be linked to various diseases in advance.