Citations

OBJECTIVE—Diminished daily physical activity explains, in part, why obesity and diabetes have become worldwide epidemics. In particular, chair use has replaced ambulation, so that obese individuals tend to sit for ∼2.5 h/day more than lean counterparts. Here, we address the hypotheses that free-living daily walking distance is decreased in obesity compared with lean subjects and that experimental weight gain precipitates decreased daily walking. RESEARCH DESIGN AND METHODS—During weight-maintenance feeding, we measured free-living walking using a validated system that captures locomotion and body movement for 10 days in 22 healthy lean and obese sedentary individuals. These measurements were then repeated after the lean and obese subjects were overfed by 1,000 kcal/day for 8 weeks. RESULTS—We found that free-living walking comprises many (∼47) short-duration (<15 min), low-velocity (∼1 mph) walking bouts. Lean subjects walked 3.5 miles/day more than obese subjects (n = 10, 10.3 ± 2.5 vs. n = 12, 6.7 ± 1.8 miles/day; P = 0.0009). With overfeeding, walking distance decreased by 1.5 miles/day compared with baseline values (−1.5 ± 1.7 miles/day; P = 0.0005). The decrease in walking that accompanied overfeeding occurred to a similar degree in the lean (−1.4 ± 1.9 miles/day; P = 0.04) and obese (−1.6 ± 1.7 miles/day; P = 0.008) subjects. CONCLUSIONS—Walking is decreased in obesity and declines with weight gain. This may represent a continuum whereby progressive increases in weight are associated with progressive decreases in walking distance. By identifying walking as pivotal in weight gain and obesity, we hope to add credence to an argument for an ambulatory future.

A prospective multicenter trial was conducted to evaluate the safety and feasibility of granulocyte colony-stimulating factor (G-CSF)–primed bone marrow (G-BM) in children receiving allogeneic bone marrow transplantation (BMT). A total of 42 children with a median age of 9.8 years (range, 0.8-17 years) were enrolled. Donors with median age of 9.2 years (range, 1.1-22 years) received 5 μg/kg per day of subcutaneous G-CSF for 5 consecutive days. BM was harvested on the fifth day. No donor experienced complications related to G-CSF administration or marrow har-vest. Median nucleated (NC) and CD34 cells infused was 6.7 × 108/kg (range, 2.4-18.5 × 108/kg) and 7.4 × 106/kg (range, 2-27.6 × 106/kg), respectively. Neutrophil and platelet engraftment was at a median of 19 days (range, 13-28 days) and 20 days (range, 9-44 days), respectively. A total of 13 (32%) patients developed grade 2 graft-versus-host disease (GVHD), and 5 (13%) of 40 evaluable patients developed chronic GVHD (3 limited and 2 extensive). Higher cell dose was not associated with increased risk of acute or chronic GVHD. Overall survival and event-free survival at 2 years were 81% and 69%, respectively. Collection of G-BM from pediatric donors is safe, and can result in high NC and CD34 cell doses that facilitate engraftment after myeloablative BMT without a discernable increase in the risk of GVHD.

ABSTRACT Obesity is one of the major health problems of our times. Elucidating the signaling mechanisms by which high‐fat caloric diet induces obesity is critical for the understanding of this condition and for the development of therapeutic strategies for its treatment. Here, we demonstrate a novel role for protein CD38 as a regulator of body weight during a high‐fat diet. CD38 is a ubiquitous enzyme that catalyzes the synthesis of second messengers and has been implicated in the regulation of a wide variety of signaling pathways. We report that CD38‐deficient mice are pro‐tected against high‐fat diet‐induced obesity owing to enhanced energy expenditure. In fact, calorimetric studies indicate that CD38‐deficient animals have a higher metabolic rate compared to control mice. Analysis of the mechanism revealed that this resistance to diet‐induced obesity is mediated at least in part via a NAD‐dependent activation of SIRT‐PGC1α axis, a well‐established cascade, involved in the regulation of mito‐chondrial biogenesis and energy homeostasis. Thus, together these results identify a novel pathway regulating body weight and clearly show that CD38 is a nearly obligatory component of the cellular cascade that led to diet‐induced obesity.—Barbosa, M. T. P., Soares, S. M., Novak, C. M., Sinclair, D., Levine, J. A., Aksoy, P., Chini, E. N. The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet‐induced obesity. FASEB J. 21, 3629–3639 (2007)

Abstract Several types of adrenocortical tumors that lead to Cushing syndrome may be caused by aberrant cyclic AMP (cAMP) signaling. We recently identified patients with micronodular adrenocortical hyperplasia who were carriers of inactivating mutations in the 2q-located phosphodiesterase 11A (PDE11A) gene. We now studied the frequency of two missense substitutions, R804H and R867G, in conserved regions of the enzyme in several sets of normal controls, including 745 individuals enrolled in a longitudinal cohort study, the New York Cancer Project. In the latter, we also screened for the presence of the previously identified PDE11A nonsense mutations. R804H and R867G were frequent among patients with adrenocortical tumors; although statistical significance was not reached, these variants affected significantly enzymatic function in vitro with variable increases in cAMP and/or cyclic guanosine 3′,5′-monophosphate levels in HeLa and HEK293 cells. Adrenocortical tissues carrying the R804H mutation showed 2q allelic losses and higher cyclic nucleotide levels and cAMP-responsive element binding protein phosphorylation. We conclude that missense mutations of the PDE11A gene that affect enzymatic activity in vitro are present in the general population; protein-truncating PDE11A mutations may also contribute to a predisposition to other tumors, in addition to their association with adrenocortical hyperplasia. We speculate that PDE11A genetic defects may be associated with adrenal pathology in a wider than previously suspected clinical spectrum that includes asymptomatic individuals. (Cancer Res 2006; 66(24): 11571-5)

OBJECTIVE. We examined the effect of activity-enhancing screen devices on children's energy expenditure compared with performing the same activities while seated. Our hypothesis was that energy expenditure would be significantly greater when children played activity-promoting video games, compared with sedentary video games. METHODS. Energy expenditure was measured for 25 children aged 8 to 12 years, 15 of whom were lean, while they were watching television seated, playing a traditional video game seated, watching television while walking on a treadmill at 1.5 miles per hour, and playing activity-promoting video games. RESULTS. Watching television and playing video games while seated increased energy expenditure by 20 ± 13% and 22 ± 12% above resting values, respectively. When subjects were walking on the treadmill and watching television, energy expenditure increased by 138 ± 40% over resting values. For the activity-promoting video games, energy expenditure increased by 108 ± 40% with the EyeToy (Sony Computer Entertainment) and by 172 ± 68% with Dance Dance Revolution Ultramix 2 (Konami Digital Entertainment). CONCLUSIONS. Energy expenditure more than doubles when sedentary screen time is converted to active screen time. Such interventions might be considered for obesity prevention and treatment.

The older population is growing faster than the population as a whole. Paid work is the main mechanism for physical activity in humans. We, therefore, wanted to ascertain whether work practices (such as employment status and the types of tasks workers perform) follow the biological decline in physical activity that occurs with aging in humans and many other species. We recorded work practices in 3352 adults in the Ivory Coast to establish how work burdens are distributed across different age groups in a community that is minimally fettered by legal constraints. We found a decrease in the amount of work performed with increasing age, and we found that elderly persons performed more skilled, less exothermic tasks than younger workers. These data mirror global workforce distribution trends expressed by age. If the trend continues, a major portion of the population will be unlikely to contribute to the labor force in the near future, producing potentially adverse economic consequences in some populations. Although the problem might be averted or at least minimized by implementing different employment policies, biological factors could overlay and supervene any economic planning.