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Purpose: This study was designed to explore age-related changes in trabecular bone score (TBS) and bone mineral density (BMD) in Chinese men through cross-sectional and longitudinal studies. Patients and Methods: We included adult men who had at least twice TBS and BMD examinations in our hospital between January 2013 and December 2020. All men were divided into an age subgroup per 10 years, comparing differences in baseline lumbar spine (LS) TBS and BMD at various parts between each age group and analyzing age-related changes in TBS and BMD during follow-up. Results: Baseline data showed that in men aged 36 to 85 years, BMD in the hip region showed a decreasing trend with age (P for trend < 0.01). However, TBS reached a high value around the age of 50, after which it decreased with age (P for trend = 0.03). During a mean follow-up of 3 years, the average annual change rate at TBS was − 0.17% in men aged 36 to 85 years, with the fastest decrease rate − 1.08% at 66 to 75 years (P < 0.05). The mean annual rate of change in LS BMD in different age subgroups increased with age (P for trend = 0.001). There was no significant decrease in mean annual change in BMD in hip regions. Conclusion: In men aged 36∼ 85 years, the trend of TBS was inconsistent with BMD. Men experience a high value of LS TBS around age 50, later than the commonly believed age of peak BMD, which may reflect developmental differences between bone microstructure and bone minerals. The TBS may be used as a better indicator of changes in bone strength than BMD in adult men at short-term follow-up. The rapid loss of TBS at age 66 to 75 may have implications for the prevention and medication of osteoporosis in men. [ABSTRACT FROM AUTHOR]

Objective: Given the rising prevalence of central obesity and the discovery that beige cells appear within white adipose tissue, strategies to enhance these energy-expending adipocytes or "browning" within white adipose depots have become of therapeutic interest to combat obesity and its associated disorders. This study focused on, the role of microRNA (miRNA)-27b-3p in human visceral adipose tissue (VAT) browning.Methods: Expression of miR-27b-3p and UCP1 in VAT and serum of humans was measured. MiR-27b-3p was overexpressed or suppressed in human visceral stromal fraction cells to analyze the potential role of miR-27b-3p.Results: UCP1 expression in human VAT decreased with elevated BMI and waist-hip ratio, whereas expression of miR-27b-3p was found to correlate positively with BMI and waist-hip ratio. High expression of miR-27b-3p was associated with reduced browning ability of human visceral adipocytes. Antagonism of miR-27b-3p led to the enhancement of browning ability in human visceral adipocytes.Conclusions: These findings highlight the decreased browning ability of VAT from humans with obesity and the role of miR-27b-3p in regulating browning of human visceral adipocytes. They suggest that miR-27b-3p should be further explored as a potential target for the treatment of central obesity. [ABSTRACT FROM AUTHOR]

Calorie restriction ( CR) increases average and maximum lifespan and exhibits an apparent beneficial impact on age-related diseases. Several studies have shown that CR initiated either in middle or old age could improve ischemic tolerance and rejuvenate the aging heart; however, the data are not uniform when initiated in young. The accurate time to initiate CR providing maximum benefits for cardiac remodeling and function during aging remains unclear. Thus, whether a similar degree of CR initiated in mice of different ages could exert a similar effect on myocardial protection was investigated in this study. C57 BL/6 mice were subjected to a calorically restricted diet (40% less than the ad libitum diet) for 3 months initiated in 3, 12, and 19 months. It was found that CR significantly reversed the aging phenotypes of middle-aged and old mice including cardiac remodeling (cardiomyocyte hypertrophy and cardiac fibrosis), inflammation, mitochondrial damage, telomere shortening, as well as senescence-associated markers but accelerated in young mice. Furthermore, whole-genome microarray demonstrated that the AMP-activated protein kinase ( AMPK)-Forkhead box subgroup 'O' ( FOXO) pathway might be a major contributor to contrasting regulation by CR initiated in different ages; thus, increased autophagy was seen in middle-aged and old mice but decreased in young mice. Together, the findings demonstrated promising myocardial protection by 40% CR should be initiated in middle or old age that may have vital implications for the practical nutritional regimen. [ABSTRACT FROM AUTHOR]

Age‐related alterations in whole body composition, particularly, reduced fat free mass (FFM) and increased fat mass (FM), lead to a progressive decline in resting energy expenditure (REE). Similarly, regional body composition and fat distribution changes with age might also contribute to an overall lower REE. This study investigated the influence of age on REE, regional body composition and fat distribution, including subcutaneous fat (SF) and visceral fat (VF), in a Chinese Han population as well as their contributions to age‐related changes in REE. One hundred and two males aged 31–83 years old underwent dual‐energy X‐ray absorptiometry (DXA) which measured whole body and regional FM and FFM. SF and VF were measured by magnetic resonance imaging (MRI) and REE by indirect calorimetry. Age was significantly negatively correlated with REE (r = −0.37), total FFM (r = −0.25), upper limbs FFM (r = −0.32), lower limbs FFM (r = −0.34) and showed positive association with trunk FFM (β=0.926). FM, SF and VF decreased in older age groups after an initial rise up to 55–65 years. REE correlated positively to FM, FFM, SF, VF and showed significant association with age (β = −0.254) independent of age‐associated changes in body composition. The regional alterations in body composition with age were explained by changes in trunk FFM (β = 0.926). Age‐related decline in REE were not solely due to alterations in FM and FFM. Therefore, the changes in regional body composition, fat distribution and REE which occur during aging could be explained by disparities in race, ethnicity, diet, physical activity, and lower specific metabolic rates of FFM components. Aging was associated with a significant decrease in resting energy expenditure (REE) and fat free mass (FFM). A decline in whole body and regional fat mass (FM) was observed with advancing age. Age‐related decline in REE was associated to a decrease in FM and FFM. Age was the main determinant of REE. [ABSTRACT FROM AUTHOR]

Sarcopenia, a progressive and systemic skeletal muscle disorder, is closely related with the incidence of cardiovascular disease (CVD) and CVD-related mortality, but its association with cardiac structure and function during aging remains unclear, particularly in the absence of serious cardiovascular diseases. This study aimed to investigate the correlation of muscle mass and muscle strength, the main components of sarcopenia, with left ventricular mass and function in Chinese subjects.A total of 265 men and 70 women (aged 25-95 years) without serious diseases that could have pronounced impact on muscle and/or cardiovascular system were included. Left ventricular mass and function were assessed by echocardiography and muscle mass and grip strength were evaluated by dual-energy X-ray absorptiometry and a Jamar hand dynamometer, respectively.Grip strength and left ventricular diastolic function, rather than left ventricular mass, demonstrated age-dependent decline in both genders. Muscle mass in males and left ventricular systolic function in females declined with age. In the multivariate-adjusted model, grip strength rather than the relative appendicular skeletal muscle mass (RASM) was positively associated with E/A ratio (r = 0.154, P = 0.019) and e´-av (r = 0.175, P = 0.008), but was negatively correlated with E/e´-av ratio (r = -0.136, P = 0.038). No significant correlation was observed between RASM, grip strength and left ventricular mass, left ventricular ejection fraction or left ventricular fractional shortening. Higher grip strength is independently associated with better left ventricular diastolic function in Chinese during aging.

Objective: Whether sarcopenia is detrimental to depression is still controversial, which may be due to the three components of the sarcopenia. Our objective was to define the correlation between depression and sarcopenia in older Chinese community dwellers., Design: The study has a cross-sectional design., Setting: The study was conducted in Jiangsu, China., Participants: A total of 101 men and 149 women aged 60 years or older were recruited., Outcome Measures: Lean tissue mass was measured by dual-energy X-ray absorptiometry. Muscle strength in the upper and lower limbs was measured by a handheld dynamometer and a chair stand test, respectively. Physical performance was assessed by gait speed and standing balance tests. Depressive mood was assessed using the Geriatric Depression Scale-30 (range 0-30)., Results: Participants in the sarcopenia group had a higher mean depression score than the normal group (p=0.002). Pearson's correlation analysis showed that depression was negatively associated with muscle strength (handgrip strength: R=-0.170, p=0.028 for women, R=-0.196, p=0.048 for men; chair stand test performance: R=0.252, p=0.002 for women, R=0.311, p=0.001 for men) and physical performance (gait speed: R=-0.200, p=0.009, standing balance test performance: R=-0.224, p=0.006, Short Physical Performance Battery (SPPB): R=-0.218, p=0.007 for women; SPPB: R=-0.252, p=0.01 for men). Multiple linear regression models revealed that depressive mood was inversely associated with chair stand test (β = 0.325, p<0.001), gait speed (β = -0.009, p=0.041) and standing balance test (β=-0.24, p=0.016) after adjusting for confounding factors, while no significant correlation was observed between depressive mood and muscle mass., Conclusion: The diagnostic components of sarcopenia-strength of the leg muscles (chair stand test) and physical performance (gait speed and standing balance test)-were associated with depressive mood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Brown adipose tissue (BAT) increases energy expenditure and is an attractive therapeutic target for obesity. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), an amplifier of local glucocorticoid activity, has been shown to modulate white adipose tissue (WAT) metabolism and function. In this study, we investigated the roles of 11β-HSD1 in regulating BAT function. We observed a significant increase in the expression of BAT-specific genes, including UCP1, Cidea, Cox7a1, and Cox8b, in BVT.2733 (a selective inhibitor of 11β-HSD1)-treated and 11β-HSD1-deficient primary brown adipocytes of mice. By contrast, a remarkable decrease in BAT-specific gene expression was detected in brown adipocytes when 11β-HSD1 was overexpressed, which effect was reversed by BVT.2733 treatment. Consistent with the in vitro results, expression of a range of genes related to brown fat function in high-fat diet-fed mice treated with BVT.2733. Our results indicate that 11β-HSD1 acts as a vital regulator that controls the expression of genes related to brown fat function and as such may become a potential target in preventing obesity.

Pharmacologic glucocorticoids (GCs) inhibit osteoblast function and induce osteoporosis. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may play a role in osteoporosis as it regulates GC action at a pre-receptor level by converting inactive GC to its active form. Further, 11β-HSD1 was found increasingly expressed in bone with age. In spite of these observations, its function in senile osteoporosis remains uncertain. In this study we constructed a lentiviral vector overexpressing mouse 11β-HSD1 and then MC3T3-E1 preosteoblast cells were infected by the negative control lentivirus and 11β-HSD1-overexpressing lentivirus, respectively. The mRNA and protein levels of 11β-HSD1 were significantly increased in MC3T3-E1 cells that were infected by 11β-HSD1-overexpressing lentivirus compared to the cells infected by the negative control lentivirus. The osteogenic differentiation of MC3T3-E1 preosteoblast cells was dramatically suppressed by 11β-HSD1 overexpression under the reductase substrate dehydrocorticosterone (DHC). The inhibition effect was similar to the inhibition of osteogenesis by over-dose GCs, including ALP activity, the ultimate calcium nodus formation as well as the expression of the osteogenic genes such as ALP, BSP, OPN and OCN. However, with addition of BVT.2733, a selective inhibitor of 11β-HSD1, all of the above osteogenic repression effects by 11β-HSD1 overexpression were reversed. Furthermore, a GC receptor antagonist RU486 also showed the similar effect, preventing inhibition of osteogenesis by 11β-HSD1 overexpression. These results demonstrated that the specific 11β-HSD1 inhibitor BVT.2733 can reverse the suppression effect towards osteogenic differentiation in 11β-HSD1 overexpressed MC3T3-E1 cells. Inhibition of 11β-HSD1 can be a new therapeutic strategy for senile osteoporosis.

Background: Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is being pursued as a new therapeutic approach for the treatment of obesity and metabolic syndrome. Therefore, there is an urgent need to determine the effect of 11β-HSD1 inhibitor, which suppresses glucocorticoid action, on adipose tissue inflammation. The purpose of the present study was to examine the effect of BVT.2733, a selective 11β-HSD1 inhibitor, on expression of pro-inflammatory mediators and macrophage infiltration in adipose tissue in C57BL/6J mice., Methodology/principal Findings: C57BL/6J mice were fed with a normal chow diet (NC) or high fat diet (HFD). HFD treated mice were then administrated with BVT.2733 (HFD+BVT) or vehicle (HFD) for four weeks. Mice receiving BVT.2733 treatment exhibited decreased body weight and enhanced glucose tolerance and insulin sensitivity compared to control mice. BVT.2733 also down-regulated the expression of inflammation-related genes including monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α) and the number of infiltrated macrophages within the adipose tissue in vivo. Pharmacological inhibition of 11β-HSD1 and RNA interference against 11β-HSD1 reduced the mRNA levels of MCP-1 and interleukin-6 (IL-6) in cultured J774A.1 macrophages and 3T3-L1 preadipocyte in vitro., Conclusions/significance: These results suggest that BVT.2733 treatment could not only decrease body weight and improve metabolic homeostasis, but also suppress the inflammation of adipose tissue in diet-induced obese mice. 11β-HSD1 may be a very promising therapeutic target for obesity and associated disease.

Current pharmacological treatments for obesity and metabolic syndrome have various limitations. Recently, adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of obesity and metabolic syndrome. Nevertheless, there is no adipose tissue-targeted 11β-HSD1 inhibitor available now. We sought to develop a new 11β-HSD1 pharmacological inhibitor that homes specifically to the white adipose tissue and aimed to investigate whether adipose tissue-targeted 11β-HSD1 inhibitor might decrease body weight gain and improve glucose tolerance in diet-induced obesity mice. BVT.2733, an 11β-HSD1 selective inhibitor was connected with a peptide CKGGRAKDC that homes to white fat vasculature. CKGGRAKDC-BVT.2733 (T-BVT) or an equimolar mixture of CKGGRAKDC and BVT.2733 (NT-BVT) was given to diet-induced obesity mice for two weeks through subcutaneous injection. T-BVT decreased body weight gain, improved glucose tolerance and decreased adipocyte size compared with vehicle treated mice. In adipose tissue T-BVT administration significantly increased adiponectin, vaspin mRNA levels; In liver T-BVT administration decreased the mRNA level of phosphoenolpyruvate carboxykinase (PEPCK), increased the mRNA levels of mitochondrial carnitine palmi-toyltransferase-I (mCPT-I) and peroxisome proliferator-activated receptorα(PPARα). No significant differences in adipocyte size and hepatic gene expression were observed after treatment with NT-BVT compared with vehicle treated mice, though NT-BVT also decreased body weight gain, improved glucose tolerance, and increased uncoupling protein-2 (UCP-2) mRNA levels in muscle. These results suggest that an adipose tissue-targeted pharmacological inhibitor of 11β-HSD1 may prove to be a new approach for the treatment of obesity and metabolic syndrome.

Studies on the relationship between obesity and bone have recently become widespread. The aim of this study was to investigate the effect of obesity on bone, utilizing a diet-induced obese mouse model, and to explore the role of free fatty acids (FFAs) in the osteogenesis/adipogenesis of mouse bone marrow-derived mesenchymal stem cells (BMSCs). An obese mouse model was established by a high-fat diet (HFD). Proximal femurs were collected at sacrifice, and bone mineral density (BMD) in the proximal femurs was measured by dual-energy X-ray absorptiometry. Bone histomorphometry was performed using undecalcified sections of the proximal femurs. The effect of obesity on the differentiation of mouse BMSCs was assessed by colony formation assays and gene expression analysis. In vitro, various osteogenic and adipogenic genes were determined by real-time quantitative PCR in mouse BMSCs after exposure to conditioned medium (CM) from FFA-treated 3T3-L1 adipocytes. Western blotting was further performed to analyze the representative protein expression of PPARγ and Runx2. BMD and trabecular thickness were significantly greater in the HFD mice than in the control mice. CFU-osteo assay showed significantly increased osteogenesis of BMSCs. The mRNA level of Runx2 was significantly higher, while PPARγ and Pref-1 were significantly lower in BMSCs from the HFD mice compared to the control mice. In mouse BMSCs, the Sox9 and Runx2 genes were significantly up-regulated after exposure to CM from FFA-treated adipocytes, while PPARγ and CEBP-α were significantly down-regulated. Osteogenesis was significantly increased, while adipogenesis was significantly decreased. In conclusion, HFD-induced obesity may play a protective role in bone formation by concomitantly promoting osteogenic and suppressing adipogenic differentiation of BMSCs through factors secreted by FFA-treated adipocytes.