Ob/
ob and
db/
db mice have different aberrations in leptin signaling that both lead to abnormalities in bone mineral density (BMD), and bone histological and histomorphometric outcomes. A few ...studies have directly compared bone metabolism in
ob/
ob and
db/
db mice, and biomechanical strength properties that are surrogate measures of fracture risk, have not been extensively studied. This study compared bone mineral content (BMC), BMD and biomechanical strength properties of femurs and lumbar vertebrae among 10 week old male
ob/
ob,
db/
db and C57Bl/6 wildtype (WT) mice. Femurs and lumbar vertebrae were specifically studied to determine if trabecular and cortical bone are regulated by leptin in a similar manner in
ob/
ob and
db/
db mice. Femurs of
ob/
ob and
db/
db mice had lower BMC, BMD and biomechanical strength properties, including peak load, compared to WT mice. In contrast, lumbar vertebrae BMC and BMD did not differ among genotypes, nor did the peak load from compression testing of an individual lumbar vertebra differ among groups. These findings suggest that leptin deficiency in adolescent male mice first results in changes in femurs, a representative long bone, and alterations in lumbar vertebrae may occur later in life.
Summary
Asthma is a complex heterogeneous disease of the airways characterized by lung inflammation, airway hyperreactivity (
AHR
), mucus overproduction, and remodeling of the airways. Group 2 ...innate lymphoid cells (
ILC
2s) play a crucial role in the initiation and propagation of type 2 inflammatory programs in allergic asthma models, independent of adaptive immunity. In response to allergen, helminths or viral infection, damaged airway epithelial cells secrete
IL
‐33,
IL
‐25, and thymic stromal lymphopoietin (
TSLP
), which activate
ILC
2s to produce type 2 cytokines such as
IL
‐5,
IL
‐13, and
IL
‐9. Furthermore,
ILC
2s coordinate a network of cellular responses and interact with numerous cell types to propagate the inflammatory response and repair lung damage.
ILC
2s display functional plasticity in distinct asthma phenotypes, enabling them to respond to very different immune microenvironments. Thus, in the context of non‐allergic asthma, triggered by exposure to environmental factors,
ILC
2s transdifferentiate to
ILC
1‐like cells and activate type 1 inflammatory programs in the lung. In this review, we summarize accumulating evidence on the heterogeneity, plasticity, regulatory mechanisms, and pleiotropic roles of
ILC
2s in allergic inflammation as well as mechanisms for their suppression in the airways.
Insulin resistance is a risk factor for colon cancer, but it is not clear which of its metabolic sequelae are involved. The objective of this study was to determine whether increased adiposity and ...elevated circulating lipids commonly seen in insulin resistance promote colon carcinogenesis independent of changes in insulin. We made use of muscle-specific insulin receptor knockout (MIRKO) mice that exhibit elevated serum triglycerides (TG), free fatty acids (FFA), and fat mass but have similar body weights, circulating glucose, and insulin and insulin sensitivity to their wild-type littermates used as controls. Seven-week-old male MIRKO mice and controls received four weekly intraperitoneal injections of either 5 mg/kg azoxymethane (AOM) to induce aberrant crypt foci (ACF) or 10 mg/kg AOM to induce tumors and were killed at 24 or 40 wk of age, respectively. The MIRKO mice displayed hyperinsulinemia at 7 wk of age and reduced insulin sensitivity at 16 wk of age compared with controls. The previously reported MIRKO phenotype developed between 16 and 24 wk of age. By 40 wk of age, however, MIRKO mice were again insulin resistant. ACF development did not differ between MIRKO mice and controls, but MIRKO mice developed significantly fewer colon tumors. Our results suggest that circulating TG and FFA are not promoters of colon tumor development. Indeed, we show that the cumulative effects of the metabolic changes that occur with knockout of the insulin receptor in muscle are associated with reduced susceptibility to colon tumorigenesis.
CLA inhibits mammary cancer and reduces body fat accumulation in rodents. It is not known whether uncoupling proteins (UCP), which are modulators of energy balance and metabolism, play a role in ...these actions of CLA. To determine the effects of dietary CLA on the expression of UCP in various tissues, 5‐wk‐old Sprague‐Dawley rats and C57BI/6 mice were fed diets containing 1% CLA for 3 wk. CLA treatment reduced adipose depot weights in both rats and mice but had no significant effects on body weight. There was a species‐specific effect of CLA on the expression of UCP. Whereas CLA did not affect the expression of UCP in most tissues in rats, mice fed CLA had increased expression of UCP2 in the mammary gland, brown adipose tissue (BAT), and white adipose tissue (WAT). Furthermore, UCP1 and UCP3 mRNA and protein levels in BAT were significantly lower in CLA‐fed mice compared to controls. Skeletal muscle UCP3 mRNA was unchanged, but UCP3 protein levels were significantly increased in mice, suggesting translational or posttranslational regulation of this protein. Results from this study suggest that alterations in the expression of UCP in mice may be related to the previously reported effects of dietary CLA in lowering adiposity and increasing FA oxidation. In rats, however, induction of UCP is not likely to be responsible for fat reduction or for the inhibitory action of CLA on mammary carcinogenesis.
Conjugated linoleic acid (CLA) is a potent inhibitor of the initiation and promotion of mammary carcinogenesis in animal models, but its role in colon carcinogenesis remains unclear. The objective of ...this study was to determine whether CLA inhibits the promotion of colon carcinogenesis. Forty male Sprague-Dawley rats were given a single dose of azoxymethane (20 mg/kg body wt ip). After 1 wk, the animals were randomized into two groups (n = 20) and fed a control AIN-93G diet or the control diet supplemented with 1% CLA at the expense of the soybean oil. After 12 wk, the animals were killed, and their colons were stained with methylene blue for aberrant crypt foci (ACF) analysis by light microscopy. The total number of ACF per animal did not differ between the control (174 ±11) and CLA (170 ± 10) groups. Furthermore, CLA did not affect the average crypt multiplicity (crypts/ACF) or the average number of ACF in any size category. However, rats fed the 1% CLA diet had significantly higher serum insulin levels at the time of sacrifice than those fed the control diet. Thus it is possible that the promoting effects of elevated serum insulin on colon carcinogenesis may have counteracted an inhibitory effect of CLA.
The objectives were to determine whether conjugated linoleic acid (CLA) inhibits the promotion phase of colon carcinogenesis and to investigate whether effects of CLA on uncoupling proteins (UCPs) ...mediate its known inhibition of mammary carcinogenesis. In the first study, AOM-treated rats were fed control or 1% CLA diets for 12 weeks and colons were analyzed for ACF. CLA-fed rats had no difference in total number or size of ACF but they had elevated serum insulin, which may have counteracted an inhibitory effect of CLA on colon carcinogenesis. In the second study, rats fed 1% CLA for 3 weeks had no changes in tissue UCP expression suggesting that UCPs are not involved in CLA's inhibition of rat mammary carcinogenesis. In mice, CLA caused increased expression of adipose UCP2 and skeletal muscle UCP3 suggesting that these proteins may be mediating the known effects of CLA on energy expenditure and energy storage.
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