1. The Role of CNS Fuel Sensing in Energy and Glucose Regulation
Daniela Cota, Karine Proulx, Randy J. Seeley 
Gastroenterology 
Volume 132, Issue 6, Pages (May 2007)
DOI: /j.gastro
Copyright © 2007 AGA Institute Terms and Conditions

2. Figure 1
The regulation of energy balance by currently available and stored fuels. In the periphery, fuels derived from recently ingested food are sensed by fuel-sensing mechanisms and stored in the form of fat in the adipose tissue. Adiposity signals, such as leptin and insulin, together with nutrients, are also sensed in the CNS, specifically in the hypothalamus. Hypothalamic sensors that detect adiposity signals and available fuels integrate this information leading to the modulation of intracellular signaling pathways that can regulate both the neuronal firing rate and the transcription of effector molecules. As a result, food intake and energy expenditure are regulated in order to maintain energy balance.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

3. Figure 2
Convergence of metabolic and hormonal signals on common hypothalamic intracellular signaling cascades. Nutrients, such as glucose, free fatty acids and branched-chain amino acids like leucine, together with hormones, such leptin and insulin, use the same hypothalamic intracellular pathways to determine anorexia and inhibition of hepatic glucose production. Hypothalamic mTOR may be regulated by nutrients directly or indirectly through the modulation of AMPK. AMPK also negatively affects the ACC-FAS pathway and the production of malonyl CoA. The downstream mediators of mTOR-induced anorexia have yet to be identified. Insulin and leptin inhibit AMPK and might regulate mTOR activity via the PI3K pathway. PI3K is also involved in modulating KATP channel activity, the function of which can be affected by nutrients, such as glucose and oleic acid. Finally, leptin-dependent activation of STAT3 represents a crucial event for the effect of leptin on food intake.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions

4. Randy Seeley, MD, PhD
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2007 AGA Institute Terms and Conditions