Mechanisms underlying current and future anti-obesity drugs Roger A.H. Adan  Trends in Neurosciences  Volume 36, Issue 2, Pages 133-140 (February 2013) DOI: 10.1016/j.tins.2012.12.001 Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 1 Simplified feeding neural circuitry. Hindbrain neural circuits (within the orange circle), including the dorsal motor nucleus of the vagus complex (DVC), the nucleus of the tractus solitarius (NTS), area postrema (AP), and parabrachial nucleus (PBN), control satiation. Amylin and pancreatic polypeptide (PP) affect satiation via their activity on the brain stem. Rostral brain areas modulate satiation via their projections on NTS and DVC [99]. In a satiated state, initiation of (palatable) food intake is elicited by injection of opioids in the ventral striatum [100] or by electrical stimulation of the lateral hypothalamus (LH) [101]. Green arrows indicate projections that stimulate feeding when activated. Red arrows indicate projections that inhibit feeding. Pro-opiomelanocortin (POMC) and neuropeptide Y (NPY)/Agouti-related protein (AgRP) neurons originate in the arcuate nucleus. Leptin, ghrelin, glucagon-like peptide 1 (Glp-1) and peptide YY3–36 (PYY3–36) act on these and other neurons. Serotonin (5HT) and noradrenalin (NOR) neurons originate in the brain stem. The mesolimbic dopamine system is shown in purple with some of its connections. Receptors are depicted in black. The hypothalamus is in green. The blue arrow indicates the mesolimbic dopamine projection. Abbreviations: D1, dopamine 1 receptor; D2, dopamine 2 receptor; HT1B, serotonin 1B receptor; HT2C, serotonin 2C receptor; HT3, serotonin 3 receptor; α1, α1 adrenoceptor; β2, β2 adrenoceptor; CB1, cannabinoid 1 receptor; μ, mu opioid receptor; κ, kappa opioid receptor; δ, delta opioid receptor. Trends in Neurosciences 2013 36, 133-140DOI: (10.1016/j.tins.2012.12.001) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure I Timeline indicating some of the main classes of anti-obesity drugs that have been introduced into the market. Trends in Neurosciences 2013 36, 133-140DOI: (10.1016/j.tins.2012.12.001) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure I Energy balance during a typical workday. Fluctuations in energy balance (with energy rising during feeding and decreasing on expenditure) during a workday for a man who spends most of his work at a desk, cycles to work, and eats three meals plus drinks and snacks during the day and in the evening. Colors in the figure on the left correspond to those in the bar graph on the right and indicate the relative amounts of energy taken in or spent. Trends in Neurosciences 2013 36, 133-140DOI: (10.1016/j.tins.2012.12.001) Copyright © 2012 Elsevier Ltd Terms and Conditions