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To examine the role of the brain stem melanocortin system in long-term energy regulation, we assessed the effects of overproduction of proopiomelanocortin (POMC) in the caudal brain stem of F344xBN rats with adult-onset obesity. Recombinant adeno-associated viral vector encoding POMC gene was delivered to the nucleus of solitary tract (NTS) in the hindbrain, and food intake, body weight, glucose and fat metabolism, brown adipose tissue thermogenesis, and mRNA levels of neuropeptides and melanocortin receptors were assessed. POMC delivery resulted in sustained reduction in food intake and body weight over 42 days and improved insulin sensitivity. At death, in recombinant adeno-associated viral vector-POMC-treated rats vs. control rats, ␣-melanocyte-stimulating hormone in NTS increased nearly 21-fold, whereas hypothalamic ␣-melanocyte-stimulating hormone remained unchanged. Visceral adiposity decreased by 37%; tissue triglyeride content diminished by 26% and 47% in liver and muscle, respectively; serum triglyeride and nonesterified fatty acids were reduced by 35% and 34%, respectively; phosphorylation of acetyl-CoA carboxylase was elevated by 63% in soleus muscle; brown adipose tissue uncoupling protein 1 increased by 30%; and melanocortin 3 receptor expression declined by 60%, whereas neuropeptide Y, agouti-related protein, and MC4 receptor mRNA levels were unchanged in the NTS. In conclusion, POMC overexpression in the NTS produces a characteristic unabated hypophagia that is uniquely different from the anorexic tachyphylaxis following POMC overexpression in the hypothalamus. The sustained anorectic response may result from absence of compensatory elements in the NTS, such as increased agouti-related protein expression, suggesting melanocortin activation of the brain stem may be a viable strategy to alleviate obesity.adult-onset obesity; proopiomelanocortin overexpression; gene delivery; brain stem THE BRAIN MELANOCORTIN PATHWAY is a key leptin target in the central nervous system and plays an essential role in the homeostatic regulation of body weight (6,8,28). Melanocortins are peptides cleaved from a common precursor, proopiomelanocortin (POMC). Rodents with POMC deficiency and humans with POMC mutations are hyperphagic and obese (15,35). The contribution of the central melanocortin system on the regulation of food intake and body weight has been attributed primarily to hypothalamic POMC neurons in the arcuate nucleus (ARC), which produce alpha-melanocyte-stimulating hormone (␣-MSH), the principal central melanocortin. ␣-MSH and its analog, melanotan II (MTII), inhibit food intake and enhance energy expenditure mainly through activation of melanocortin 3 (MC3R) and 4 (MC4R) receptors in the hypothalamus (5). However, the central melanocortin system is not limited to the hypothalamus. POMC neurons and ␣-MSH are both found within the commissural region of the nucleus of the solitary tract (NTS) in the brain stem (11,24) where MC4Rs are also expressed (14,22). Thus melanocortin signaling within the NTS may contr...

Mercury concentrations in size fractions of airborne particulate matter obtained from urban and suburban sites in Beijing in 2003 and 2004 are presented in this paper. The average concentrations of total particulate mercury were 1.1870.82 ng m À3 with a range of 0.18-3.51 ng m À3 at the urban site and 0.6870.62 ng m À3 with a range of 0.13-2.40 ng m À3 at the suburban site. This is much higher than what is found in Europe and Northern America. The results implie that significant anthropogenic sources in Beijing contribute to the concentration of particulate mercury in air and therefore, to the mercury deposition in this region. There are clear seasonal variations in concentration of particulate mercury with highest concentrations in winter at urban and suburban sites. This illustrates the important contribution from coal burning to particulate mercury during the heating season. The mercury concentration in each size fraction of airborne particulates was closely related to its size range. The highest mercury concentration was found in the size fraction less than 1.1 mm with average concentrations of 0.5970.50 and 0.2970.26 ng m À3 at the urban and suburban sites, respectively. The mercury in this size fraction accounts for 45.779.5% and 41.978.2% of the total particulate mercury, respectively. This implies that a large fraction of the particulate mercury in this area can be transported long range before it becomes deposited. Based on the concentrations of size-fractionated particulate mercury in ambient air, the dry deposition fluxes of mercury were estimated to 407 mg m À2 a À1 at the urban site and 270 mg m À2 a À1 at the suburban site. More than 90% of the deposition flux came from particles larger than 1.1 mm despite a substantial fraction of the Hg found in particles less than 1.1 mm.