Metabolic Regulation

When I prepared the second edition of this book, published in 2003, it seemed that

there had been quite a revolution in metabolism since the first edition. A major discov-
ery had been the hormone leptin, and with it recognition of the role of adipose tissue

as an endocrine organ. As I started work on this third edition, I had the feeling that not
so much had changed. However, I soon came to realize that this was not true. In part
through the increasing use of genetically-engineered mice, especially those that lack a
particular gene, we have been led to a new appreciation of several metabolic pathways

that we thought were well understood. Adipose tissue again provides a perfect exam-
ple. Fat mobilization, when I wrote the second edition, was thought to depend on

the enzyme hormone-sensitive lipase (HSL). Then several researchers produced mice
lacking HSL: and, to everyone’s surprise, they were relatively normal. This led to the
discovery of another enzyme involved in fat mobilization, adipose triglyceride lipase.
Bernard Thorens (University of Lausanne) has challenged my understanding of liver
metabolism by producing a mouse lacking the glucose transporter GLUT2. Glucose
release from the hepatocytes is relatively normal. There are many more examples,
mostly now also shown to translate into human metabolism.