lem. There are about one billion adults that are overweight with a body mass index (BMI) over 25, and 300 million are obese with a BMI over 30 (http://www.who.int). Today there are more people overweight than underweight. It causes costly health problems, reduces life expectancy, and is associated with stigma and discrimination, which has a major effect on the quality of life. Obesity and overweight substantially increase the risk of morbidity from hypertension, dyslipidemia, type 2 diabetes, and coronary heart disease. Obesity is also important for the development of obstructive sleep apnea and respiratory problems, gallbladder disease, osteoarthritis, and nonalcoholic fatty liver disease as well as endometrial, breast, prostate, and colon cancers.There are several genes associated with obesity on the human obesity map (1) such as the melanocortin 4 receptor (MC4R), leptin and the leptin receptor. However, the contribution of each specific gene to obesity is low, being highest for the MC4R gene ranging from 1-6% (2). The overall inheritability of BMI is estimated to be about 50 -60%. Recently, three reports have shown a strong association of a singlenucleotide polymorphism (SNP) in a gene called FTO with both childhood and adult obesity. Frayling and colleagues (3) performed a genome-wide association study for about 490,000 autosomal SNPs in a type 2 diabetes population in the United Kingdom. They found that SNP rs9939609 in the FTO gene was strongly associated with type 2 diabetes, but this allele was also strongly associated with an increased BMI. The association between this FTO SNP and type 2 diabetes was abolished by adjustment for the BMI, suggesting that it was due to the increased BMI. The association of this variant with the BMI was replicated in 13 cohorts with over 38,000 individuals. Interestingly, 16% of the adults who were homozygous for this SNP weighed about 3 kg more and had 1.67-fold increased odds of obesity. This association was observed from age 7 yr upward, and it reflects a specific increase in fat mass (3). Independently, Dina et al. (4) found another SNP, rs1121980, in the first intron of the FTO gene, that was strongly associated with severe (BMI Ͼ 40) adult obesity with odds ratio of 1.55 in a population of French individuals of European ancestry). Further genotyping showed a similarly strong association of several SNPs in a cohort of about 900 severely obese adults and 2700 nonobese French controls. Three of the four most significantly associated SNPs (rs17817449, rs3751812, and rs1421085) are puta-

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Our objective was to find out if central injection of neuropeptide Y (NPY) would alter brown fat thermogenesis and white fat lipoprotein lipase activity. The following three groups of Sprague-Dawley rats received five injections over 24 h into the right lateral ventricle: 1) NPY (5 micrograms/injection) and ad libitum food; 2) NPY (5 micrograms/injection) and food restricted to control intake; 3) saline injection and ad libitum food. The NPY ad libitum-fed group consumed more food than the saline controls or NPY food-restricted animals. Brown fat thermogenic activity, assessed by GDP binding, was decreased relative to saline controls in both NPY-treated groups. White fat lipoprotein lipase activity was greatly increased in both NPY treatment groups compared with saline controls. The NPY effects on brown and white fat were not explained by measures of serum insulin, glucagon, glucose, or other metabolites. In a follow-up experiment, we asked whether food was necessary for expression of the NPY effects. Brown fat mitochondrial GDP binding indicated NPY effect even when no food was ingested. We conclude that intracerebroventricular administration of NPY promotes white fat lipid storage and decreases brown fat thermogenesis in addition to its known effect of stimulating food intake.

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