Body composition changes and inhibition of fat development in vivo implicates androgen in regulation of stem cell lineage allocation

Androgens regulate body composition in youth and declining testosterone that occurs with aging is associated with muscle wasting, increased fat mass and osteopenia. Transgenic mice with targeted androgen receptor (AR) over-expression in mesenchymal stem cells (MSC) were generated to explore the role of androgen signaling in the regulation of body composition. Transgenic males, but not females, were shorter and have reduced body weight and visceral fat accumulation. Dual-energy X-ray absorptiometry (DXA) revealed significant reductions in fat mass with a reciprocal increase in lean mass, yet no difference in food consumption or locomotor activity was observed. Adipose tissue weight was normal in brown fat but reduced in both gonadal and perirenal depots, and reduced hyperplasia was observed with smaller adipocyte size in visceral and subcutaneous white adipose tissue. Although serum leptin, adiponectin, triglyceride, and insulin levels were no different between the genotypes, intraperitoneal glucose tolerance testing (IPGTT) showed improved glucose clearance in transgenic males. High levels of the AR transgene are detected in MSCs but not in mature fat tissue. Reduced fibroblast colony forming units indicate fewer progenitor cells resident in the marrow in vivo. Precocious expression of glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT enhancer-binding protein α (C/EBPα) was observed in proliferating precursor cultures from transgenic mice compared to controls. In more mature cultures, there was little difference between the genotypes. We propose a mechanism where enhanced androgen sensitivity can alter lineage commitment in vivo to reduce progenitor number and fat development, while increasing the expression of key factors to promote smaller adipocytes with improved glucose clearance.     

中国乡村汉族脂肪质量指数与瘦体质量指数的地理性分布

2009-2013年测量了中国36个汉族乡村族群的体质数据值,计算了脂肪质量指数和瘦体质量指数,进行了乡村汉族人的脂肪质量指数、瘦体质量指数与纬度的相关分析。研究结果表明:男性瘦体质量指数与纬度呈正相关(P0.05)。女性的脂肪质量指数、瘦体质量指数与纬度均呈正相关(P<0.01)。从南方到北方,男性瘦体质量指数呈线性增长是导致男性体质量指数与纬度相关的原因。女性瘦体质量指数、脂肪质量指数均呈线性增长,共同导致女性体质量指数与纬度的相关。     

Age variations in the relation of body mass indices to estimates of body fat and muscle mass

In some chronic disease studies, distinctions have been made regarding the importance of body mass index (BMI) as a risk factor in younger versus older men and women. In order to determine the significance of these differences in BMI-disease associations, we determined the extent of age-dependent variations in the relation of BMIs to body composition in large probability samples of U.S. men and women from the First and Second U.S. National Health and Nutrition Examination Surveys (NHANES I and II). BMIs are more highly correlated with estimates of body fat in younger than in older men and women, and with muscle mass in older than in younger adults. Caution should be exercised in interpreting the significance of BMI as a risk factor for chronic disease, particularly in comparison of age groups.     

Enhanced UV‐B radiation during pupal stage reduce body mass and fat content,while increasing deformities,mortality and cell death in female adults of solitary bee Osmia bicornis

The effects of enhanced UV‐B radiation on the oogenesis and morpho‐anatomical characteristics of the European solitary red mason bee Osmia bicornis L. (Hymenoptera: Megachilidae) were tested under laboratory conditions. Cocooned females in the pupal stage were exposed directly to different doses (0, 9.24, 12.32, and 24.64 kJ/m²/d) of artificial UV‐B. Our experiments revealed that enhanced UV‐B radiation can reduce body mass and fat body content, cause deformities and increase mortality. Following UV exposure at all 3 different doses, the body mass of bees was all significantly reduced compared to the control, with the highest UV dose causing the largest reduction. Similarly, following UV‐B radiation, in treated groups the fat body index decreased and the fat body index was the lowest in the group receiving the highest dose of UV radiation. Mortality and morphological deformities, between untreated and exposed females varied considerably and increased with the dose of UV‐B radiation. Morphological deformities were mainly manifested in the wings and mouthparts, and occurred more frequently with an increased dose of UV. Cell death was quantified by the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (DNA fragmentation) during early stages of oogenesis of O. bicornis females. The bees, after UV‐B exposure exhibited more germarium cells with fragmented DNA. The TUNEL test indicated that in germarium, low doses of UV‐B poorly induced the cell death during early development. However, exposure to moderate UV‐B dose increased programmed cell death. In females treated with the highest dose of UV‐B the vast majority of germarium cells were TUNEL‐positive.     

Combining anticancer agents photodynamic therapy and LCL85 leads to distinct changes in the sphingolipid profile, autophagy, caspase-3 activation in the absence of cell death, and long-term sensitization

Two anticancer agents, LCL85 and photodynamic therapy (PDT) were combined to test whether the combination PDT/LCL85 evokes changes in the sphingolipid (SL) profile and promotes cell death. Treatment of SCCVII mouse squamous carcinoma cells using the silicone phthalocyanine Pc 4 for PDT induced increases in the prodeath global ceramides/dihydroceramides (DHceramides), and no changes in the prosurvival sphingosine-1-phosphate (S1P). In contrast, after LCL85, the levels of most ceramides and DHceramides were reduced, whereas the levels of S1P were increased. After PDT/LCL85 the levels of global ceramides and DHceramides, and of S1P, were restored to resting levels. PDT/LCL85 also enhanced the levels of C18-, C20-, and C20:1-ceramide, and C18-DHceramide. Treatment with PDT, with or without LCL85, led to substantial reductions in sphingosine levels. PDT/LCL85 induced enhanced autophagy and caspase-3 activation. None of the treatments affected short-term viability of cells. In contrast, long-term clonogenic survival was reduced not only after PDT or LCL85, but even more after PDT/LCL85. Overall, our data show that short-term exposure to PDT/LCL85 led to distinct signature effects on the SL profile, enhanced autophagy, and caspase-3 activation without cell death. Long-term exposure to PDT/LCL85 enhanced overall cell killing, supporting translational potential of PDT/LCL85.