A New Probe of the Molecular Gas in Galaxies: Application to M101

Recent studies of nearby spiral galaxies suggest that photodissociation regions (PDRs) are capable of producing much of the observed HI in galaxy disks. In that case, measurements of the HI column density and the far-ultraviolet (FUV) photon flux provide a new probe of the volume density of the local underlying H_2. We develop the method and apply it to the giant Scd spiral M101 (NGC 5457). We find that, after correction for the best-estimate gradient of metallicity in the ISM of M101 and for the extinction of the ultraviolet emission, molecular gas with a narrow range of density from 30-1000 cm^-3 is found near star- forming regions at all radii in the disk of M101 out to a distance of 12' (approximately 26 kpc), close to the photometric limit of R_25 = 13.5'. In this picture, the ISM is virtually all molecular in the inner parts of M101. The strong decrease of the HI column density in the inner disk of the galaxy at R_G < 10 kpc is a consequence of a strong increase in the dust-to-gas ratio there, resulting in an increase of the H_2 formation rate on grains and a corresponding disappearance of hydrogen in its atomic form.Comment: accepted for publication in The Astrophysical Journal (1 August 2000); 29 pages including 20 figures (7 gif); AAS LaTex; contact authors for full resolution versions of gif figure

Regulation of Lean Mass, Bone Mass, and Exercise Tolerance by the Central Melanocortin System

Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO). We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO) wild type mice with equivalent fat mass. To examine potential sources of the increased lean mass in MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters increase with age in MC4RKO mice, which likely contributes to increases in lean body mass. We functionally characterized the increased lean mass in MC4RKO mice by examining their capacity for treadmill running. MC4R deficiency results in a decrease in exercise performance. No changes in the ratio of oxidative to glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly reduced heart rate, which may underlie their impaired exercise performance. The reduced exercise capacity we report in the MC4RKO mouse has potential clinical ramifications, as efforts to control body weight in humans with melanocortin deficiency may be ineffective due to poor tolerance for physical activity

Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic–pituitary–adrenal axis

Systemic and CNS-delimited inflammation triggers skeletal muscle catabolism in a manner dependent on glucocorticoid signaling

Maternal High Fat Diet Is Associated with Decreased Plasma n–3 Fatty Acids and Fetal Hepatic Apoptosis in Nonhuman Primates

To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6∶n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6∶n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate