The role of hypoleptinemia in the psychological and behavioral adaptation to starvation: Implications for anorexia nervosa

The ob gene product, leptin, is an important circulating signal for the regulation of body weight. To identify high affinity leptin-binding sites, we generated a series of leptin-alkaline phosphatase (AP) fusion proteins as well as [125I]leptin. After a binding survey of cell lines and tissues, we identified leptin-binding sites in the mouse choroid plexus. A cDNA expression library was prepared from mouse choroid plexus and screened with a leptin-AP fusion protein to identify a leptin receptor (OB-R). OB-R is a single membrane-spanning receptor most related to the gp130 signal-transducing component of the IL-6 receptor, the G-CSF receptor, and the LIF receptor. OB-R mRNA is expressed not only in choroid plexus, but also in several other tissues, including hypothalamus. Genetic mapping of the gene encoding OB-R shows that it is within the 5.1 cM interval of mouse chromosome 4 that contains the db locus.

Striding bipedalism is a key derived behaviour of hominids that possibly originated soon after the divergence of the chimpanzee and human lineages. Although bipedal gaits include walking and running, running is generally considered to have played no major role in human evolution because humans, like apes, are poor sprinters compared to most quadrupeds. Here we assess how well humans perform at sustained long-distance running, and review the physiological and anatomical bases of endurance running capabilities in humans and other mammals. Judged by several criteria, humans perform remarkably well at endurance running, thanks to a diverse array of features, many of which leave traces in the skeleton. The fossil evidence of these features suggests that endurance running is a derived capability of the genus Homo, originating about 2 million years ago, and may have been instrumental in the evolution of the human body form.

Morbidity and mortality rates in patients with eating disorders are thought to be high, but exact rates remain to be clarified. To systematically compile and analyze the mortality rates in individuals with anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS). A systematic literature search, appraisal, and meta-analysis were conducted of the MEDLINE/PubMed, PsycINFO, and Embase databases and 4 full-text collections (ie, ScienceDirect, Ingenta Select, Ovid, and Wiley-Blackwell Interscience). English-language, peer-reviewed articles published between January 1, 1966, and September 30, 2010, that reported mortality rates in patients with eating disorders. Primary data were extracted as raw numbers or confidence intervals and corrected for years of observation and sample size (ie, person-years of observation). Weighted proportion meta-analysis was used to adjust for study size using the DerSimonian-Laird model to allow for heterogeneity inclusion in the analysis. From 143 potentially relevant articles, we found 36 quantitative studies with sufficient data for extraction. The studies reported outcomes of AN during 166 642 person-years, BN during 32 798 person-years, and EDNOS during 22 644 person-years. The weighted mortality rates (ie, deaths per 1000 person-years) were 5.1 for AN, 1.7 for BN, and 3.3 for EDNOS. The standardized mortality ratios were 5.86 for AN, 1.93 for BN, and 1.92 for EDNOS. One in 5 individuals with AN who died had committed suicide. Individuals with eating disorders have significantly elevated mortality rates, with the highest rates occurring in those with AN. The mortality rates for BN and EDNOS are similar. The study found age at assessment to be a significant predictor of mortality for patients with AN. Further research is needed to identify predictors of mortality in patients with BN and EDNOS.