ENERGY BALANCE. S. Zahedi Endocrine Research Center Research Institute for Endocrine Sciences Shaheed Beheshti University of Medical Sciences 2 nd obesity Congress 29-30- Oct. 2009 Tehran-Iran.
Endocrine Research Center
Research Institute for Endocrine Sciences
ShaheedBeheshti University of Medical Sciences
2nd obesity Congress
29-30- Oct. 2009
Barry R. Bloom (2000)
Each individual has his or her predetermined energy ration= if some body uses slowly, lasts longer
(many genes, each with small effect)
Basal metabolism: energy expenditure of a subject relaxed and at rest, at thermoneutrality, 8–12 hours after last food ingestion.
Adaptive thermogenesis: energy dissipated as heat in response to environmental changes.
Control systems in the body
ARC: arcuate nucleus, PVN: paraventricular nucleus, PFA: perfornical area, FX: fornix, LHA: lateral hypothalamic area, VMN: ventromedial nucleus, DMN: dorsomedial nucleus, AM: amygdala, CC: corpus callosum, OC: optic chiasm, SE: septum, TH: thalamus, 3V: third ventricle
from POMC neurons
Metabolic activity increases to burn fat
Metabolic activity decreases limiting fat burning
AGRP from hunger neurons
Block MSH binding
SNPC: substantia nigra pars compacta
VTA: ventral tegmental area
Opioids and amphetamines remove a GABAnergic block on dopamine production. These drugs suppress appetite, and were initially used to treat obesity. In humans, BMI is anti-correlated with #D2 receptors in the striatum.
Arc destruction causes weight gain.
Response to weight loss bidirectional; weight gain unidirectional.
DMc4r=> weight gain whereas Dnpy=>no weight loss.
AgRP/Npy neurons are more sensitive to adiposity signals than Pomc/Cart neurons.
Anabolic pathways are required for intact responses to negative energy balance (IDDM causes negative energy balance in Npy-/- mice).
Anabolic pathways are required for response to decreased leptin (Npy-/- over ob/ob mice show reduced hyperphagia).
Orlistat (interferes with fatty acid hydrolysis); => moderate clinical effects; side effects include gas/diaharrea.
Sibutramine (central norepinephrine/serotonin RI); => moderate clinical effects; side effects include tachycardia and hypertension.
Roux-en-Y gastric bypass (absorption and hormonal).
4. Rimonabant (Acomplia; CR1 endocannabinoid antagonsist).
(Morash et al, 1999;Ur et al, 2002).
and shows a diurnal rhythm .