dc.description.abstract
Control of energy metabolism is crucial for optimal functioning of organs and tissues.
Amongst all nutrients, glucose is the principal energy source for most cells and, therefore,
minimum blood glucose levels must be guaranteed. Alterations in glycaemia can lead to
hyperglycaemic states (producing protein glycosylation and toxicity in glucose-sensitive
cells) or hypoglycaemic states (that can affect brain function), both harmful. Therefore,
mechanisms must exist to keep glycaemia in a narrow physiological range (4-8 mM)
independently of the nutritional state. To achieve control of blood glucose levels, our body
has a complex, interorgan signaling system using nutrients (glucose, lipids, amino acids),
hormones (insulin, glucagon, ghrelin, etc.) and the autonomic nervous system. In response
to these signals, organs and tissues (mainly intestine, endocrine pancreas, liver, skeletal
muscle, adipose tissue, brain and adrenal glands) adapt their function to energetic
requirements.
The liver plays a pivotal role in the maintenance of glucose homeostasis by continuously
adapting its metabolism to energetic needs. In the fed state, when blood glucose levels are
high and there is insulin, liver takes-up part glucose to replenish glycogen stores. Besides,
when glucose stores are full, the liver has the capacity to synthesize lipids de novo from
glucose for-long term energy storage. Lipids are packaged in very low-density lipoprotein
(VLDL) particles and then transported to the adipose tissue. Conversely during starvation,
when glycaemia falls and glucagon increases, the liver produces glucose to maintain
circulating glucose levels by breaking down glycogen stores or by synthesizing glucose de
novo through gluconeogenesis. Gluconeogenesis, as an energy-consuming pathway, is
linked to -oxidation of fatty acids (fuel supplier pathway)...
