SignificanceThe only known homeostatic regulator of fat mass is the leptin system. We hypothesized that there is a second homeostat regulating body weight with an impact on fat mass. In this study we have added and removed weight loads from experimental animals and measured the effects on the biological body weight. The results demonstrate that there is a body weight homeostat that regulates fat mass independently of leptin. As the body weight-reducing effect of increased loading was dependent on osteocytes, we propose that there is a sensor for body weight in the long bones of the lower extremities acting as “body scales.” This is part of a body weight homeostat, “gravitostat,” that keeps body weight and body fat mass constant.
Using polyimide as host in a guest-host thin film we demonstrate the first poled-polymer electro-optic response stable at temperatures up to 150 °C (samples poled and cured at 250 °C). A coplanar-electrode poling geometry is used so that the molecular alignment of the guest dye between the electrodes is coincident with the free volume of the host. We hypothesize that ‘‘high’’ temperature poling during the imidization process, when the polyimide forms rings and densifies, accounts for the excellent poled response stability.
Wingless-type MMTV integration site family (WNT)16 is a key regulator of bone mass with high expression in cortical bone, and Wnt16 −/− mice have reduced cortical bone mass. As Wnt16 expression is enhanced by estradiol treatment, we hypothesized that the bone-sparing effect of estrogen in females is WNT16-dependent. This hypothesis was tested in mechanistic studies using two genetically modified mouse models with either constantly high osteoblastic Wnt16 expression or no Wnt16 expression. We developed a mouse model with osteoblast-specific Wnt16 overexpression (Obl-Wnt16). These mice had several-fold elevated Wnt16 expression in both trabecular and cortical bone compared with wild type (WT) mice. OblWnt16 mice displayed increased total body bone mineral density (BMD), surprisingly caused mainly by a substantial increase in trabecular bone mass, resulting in improved bone strength of vertebrae L 3 . Ovariectomy (ovx) reduced the total body BMD and the trabecular bone mass to the same degree in Obl-Wnt16 mice and WT mice, suggesting that the bone-sparing effect of estrogen is WNT16-independent. However, these bone parameters were similar in ovx OblWnt16 mice and sham operated WT mice. The role of WNT16 for the bone-sparing effect of estrogen was also evaluated in Wnt16 −/− mice. Treatment with estradiol increased the trabecular and cortical bone mass to a similar extent in both Wnt16 −/− and WT mice. In conclusion, the bone-sparing effects of estrogen and WNT16 are independent of each other. Furthermore, loss of endogenous WNT16 results specifically in cortical bone loss, whereas overexpression of WNT16 surprisingly increases mainly trabecular bone mass. WNT16-targeted therapies might be useful for treatment of postmenopausal trabecular bone loss.WNT16 | estrogen | cortical bone | trabecular bone | transgenic mice B oth estrogen and wingless-type MMTV integration site family (WNT)16 are crucial regulators of bone mass in women (1-5). The bone-sparing effect of estrogen is primarily mediated via estrogen receptor-α (ERα) (6). Estrogen-deficiency leads to rapid bone loss and contributes significantly to the development of postmenopausal osteoporosis that can be prevented by estradiol treatment. However, this treatment is associated with side effects such as breast cancer and thromboembolism (7,8).The WNTs are a family of secreted glycoproteins that consists of 19 members in mammals, and which mediates autocrine and paracrine effects by binding to frizzled (Fzd) receptors and LDL-related protein 5/6 (LRP5/6) coreceptors (9). During the last decade, several lines of clinical and preclinical evidence have indicated that WNT signaling is critical in bone development and in the regulation of adult bone homeostasis (10-20) and modulation of WNT signaling has emerged as a promising strategy for increasing bone mass (21-23). Crosstalk and synergy between ERα signaling and the WNT pathways have been described (24-26). In the brain, estrogen signaling activates WNT by down-regulating dickkopf-1 (Dkk1), a WNT antagonist, to pr...
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