Mitochondrial Dysfunction and Diabetes: Is Mitochondrial Transfer a Friend or Foe?

Obesity, insulin resistance and type 2 diabetes are accompanied by a variety of systemic and tissue-specific metabolic defects, including inflammation, oxidative and endoplasmic reticulum stress, lipotoxicity, and mitochondrial dysfunction. Over the past 30 years, association studies and genetic manipulations, as well as lifestyle and pharmacological invention studies, have reported contrasting findings on the presence or physiological importance of mitochondrial dysfunction in the context of obesity and insulin resistance. It is still unclear if targeting mitochondrial function is a feasible therapeutic approach for the treatment of insulin resistance and glucose homeostasis. Interestingly, recent studies suggest that intact mitochondria, mitochondrial DNA, or other mitochondrial factors (proteins, lipids, miRNA) are found in the circulation, and that metabolic tissues secrete exosomes containing mitochondrial cargo. While this phenomenon has been investigated primarily in the context of cancer and a variety of inflammatory states, little is known about the importance of exosomal mitochondrial transfer in obesity and diabetes. We will discuss recent evidence suggesting that (1) ti