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.

Inhibition of autophagy with chloroquine dysregulates mitochondrial quality control and energetics in adipocytes.

Autophagy is a complex degradation pathway through which damaged or dysfunctional proteins and organelles are removed. Its pharmacological modulators have been extensively used in a wide range of basic research and preclinical studies. However, the effects of these inhibitors on metabolism, in addition to autophagy inhibition, are not fully elucidated. Chloroquine is a clinically relevant compound that inhibits autophagy by preventing the fusion of autophagosomes with lysosomes. In this study, we aimed to examine the effect of chloroquine on mitochondrial quality control and respiratory function by utilizing 3T3-L1 mouse adipocytes treated with chloroquine at various time points. We found that chloroquine could disturb genes related to mitochondrial fission, biogenesis, and mitophagy, leading to mitochondrial DNA damage. Although the inhibition of autophagy by chloroquine resulted in an increased prohibitin expression, respiratory function was downregulated in a time-dependent manner. Moreover, chloroquine treatment induced oxidative stress, apoptosis, and metabolic dysregulation. These data demonstrated that chloroquine significantly affected mitochondrial respiratory function and metabolism, which was consistent with impaired mitochondrial quality associated with autophagy inhibition.

(E)-ß-borylstyrene in the Diels-Alder reaction with 3,5-dibromo-2-pyrone for the syntheses of (±)-1-epi-pancratistatin and (±)- pancratistatin.

New synthetic routes to (±)-1-epi-pancratistatin and (±)-pancratistatin were devised using (E)-ß-borylstyrene as a dienophile for the key Diels-Alder reaction with 3,5-dibromo-2-pyrone. The boronate in the cycloadduct was oxidized to provide the pivotal C1-hydroxyl group of the titled compounds.