To investigate the feasibility of trkB agonism as a therapeutic approach for human obesity, we conducted a series of experiments using NT4, BDNF and TrkB agonistic antibody in 3-Methylsalicylic acid several species of non-human primates. Both NT4 and BDNF, when delivered into the brain directly, suppressed food consumption in the lean monkeys. Contrary to our expectation, however, NT4 and TrkB agonistic antibody significantly increased food intake, body weight, fat mass and circulating leptin levels in the lean monkeys and even in the obese Cefdinir baboons. Further analysis suggested a novel, peripherally accessible, orexigenic TrkB system, which when activated can counter-balance the central, anorexigenic TrkB system. The findings described here suggest the existence in the primates of a novel, peripherally accessible, orexigenic and proobesity TrkB axis that opposes the traditional, centrally located anorexigenic TrkB axis. Both arms of the system utilize the TrkB signaling pathway and the metabolic end result would be determined by the relative strength of differentially localized TrkB signals. To our knowledge, this represents the first example in primates of diametrically opposite metabolic and behavioral outcomes mediated by the same signaling pathway via spatial compartmentalization. The anatomical sites of action for the peripherally accessible, orexigenic TrkB signal are currently unknown, but may include the enteric nervous system, the pancreatic and gut neuro-endocrine system, the vagal nerve and/or the circumventricular organs. The default state of the TrkB system in the whole body appears to be anorexigenic as indicated by the fact that rodents or humans carrying a loss of function allele of BDNF or TrkB locus exhibited early onset obesity and hyperphagia. However, the anorexigenic TrkB stimulus, which is mediated by BDNF in the VMH, is under dietary control and was shown to be suppressed following fasting in mice.he AhpC-GFP fusion contained only 36 residues of AhpC, and CC3691-GFP contained 28 residues of CC3691, yet each of these fusions was localized in the same pattern as the full-length proteins. It has been demonstrated that short peptides, or locons, can target an exogenous protein to a precise location in a bacterial cell. These data indicate that endogenous proteins use locon signals as well.