Around 15 years ago, the lab of David Kelley, MD, then at the University of Pittsburgh, had a hunch that what really matters for metabolic health might be the cell's ability to select the right fuel for the right physiological setting (i.e. fasting or feeding, exercise or not). They found that in individuals who where obese or had type II diabetes, their mitochondria had lost the capacity to make this decision. In other words, mitochondria were unable to efficiently direct traffic. This is known as metabolic inflexibility and it has been linked with numerous ailments such as obesity, heart disease, and disorders of the liver and ovaries.