Circulating microRNAs (miRNAs) are emerging biomarkers for type 2 diabetes mellitus (T2DM). However, a comprehensive characterization of the serum miRNA profile in patients with T2DM-associated microvascular disease (T2DMC) has rarely been reported. In this study, we obtained serum samples from 184 T2DM patients (92 with microvascular complications and 92 free of complications) and 92 age/gender-matched controls. The levels of 754 miRNAs were initially analyzed using a TaqMan Low Density Array (TLDA) in three pooled samples from 24 T2DM patients, 24 T2DMC patients and 24 controls. Markedly upregulated miRNAs in the patients’ groups were subsequently validated individually by quantitative reverse-transcription PCR (RT-qPCR) in the same samples used for TLDA and further confirmed in another larger cohort consisting of 68 patients with T2DM, 68 patients with T2DMC and 68 controls. Five miRNAs were significantly upregulated in T2DM patients (p < 0.05) including miR-661, miR-571, miR-770-5p, miR-892b and miR-1303. Moreover, the levels of the five miRNAs were higher in patients with complications than in those without complications. Regression analyses revealed the five miRNAs were significantly correlated with microvascular complications (p < 0.05). The five serum miRNAs identified in our study hold potential as auxiliary biomarkers and novel risk factors for T2DM-associated microvascular complications.
Brown adipose tissue (BAT) increases energy expenditure and is an attractive therapeutic target for obesity. 11b-Hydroxysteroid dehydrogenase type 1 (11b-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 11b-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 11b-HSD1)-treated and 11b-HSD1-deficient primary brown adipocytes of mice. By contrast, a remarkable decrease in BAT-specific gene expression was detected in brown adipocytes when 11b-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 11b-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.
Whether fat is beneficial or detrimental to bones is still controversial, which may be due to inequivalence of the fat mass. Our objective is to define the effect of body fat and its distribution on bone quality in healthy Chinese men. A total of 228 men, aged from 38 to 89 years, were recruited. BMD, trabecular bone score (TBS), and body fat distribution were measured by dual-energy X-ray absorptiometry. Subcutaneous and visceral fat were assessed by MRI. In the Pearson correlation analysis, lumbar spine BMD exhibited positive associations with total and all regional fat depots, regardless of the fat distribution. However, the correlation disappeared with adjusted covariables of age, BMI, HDL-C, and HbA1c%. TBS was negatively correlated with fat mass. In multiple linear regression models, android fat (and not gynoid, trunk, or limbs fat) showed significant inverse association with TBS (β = −0.611, P < 0.001). Furthermore, visceral fat was described as a pathogenic fat harmful to TBS, even after adjusting for age and BMI (β = −0.280, P = 0.017). Our findings suggested that body fat mass, especially android fat and visceral fat, may have negative effects on bone microstructure; whereas body fat mass contributes to BMD through mechanical loading.
BackgroundInhibition 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 FindingsC57BL/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/SignificanceThese 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.
Background: Sarcopenia is typically defined as the loss of muscle mass, strength and low physical performance with aging. Ultrasound is a safe and easy method for evaluating muscle mass and quality by muscle thickness (MT) and pennation angle (PA), respectively. Although the positive correlations between MT and muscle mass and handgrip strength were observed, the relationship between MT, PA and physical performance remains unclear. Purpose: This study aimed to investigate the correlation of aforementioned ultrasound parameters with muscle mass, muscle strength and physical performance and explore the utility of ultrasound in predicting sarcopenia. Patients and methods: A total of 265 elderly Chinese community dwellers were included. MT of both forearm and lower leg as well as PA of gastrocnemius was assessed by ultrasound. Muscle mass was assessed by dual-energy X-ray absorptiometry. Muscle strength was measured by a Jamar hand dynamometer. Physical performance was assessed by the Short Physical Performance Battery (SPPB). Results: Anterior radial MT in men and regional MTs except posterior fibula in women were negatively correlated with the age. No significant correlation was observed between PA and the age in both genders. Posterior tibial MT and posterior fibula MT were positively correlated with the relative appendicular skeletal muscle mass in men and women, respectively. Anterior ulnar MT was positively correlated with grip strength in both genders. Moreover, gastrocnemius medialis PA showed a positive association with gait speed and SPPB in women but not in men. Conclusion: A combination of posterior fibula MT, anterior ulnar MT and gastrocnemius medialis PA measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly women. In addition, a combination of posterior tibial MT and anterior ulnar MT measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly men.
BackgroundAs the general population is aging worldwide, the incidence of sarcopenia and osteoporosis is also rapidly increasing. Studies have found the link between sarcopenia and osteoporosis, but the relationship between sarcopenia and osteoporosis, especially bone microarchitecture, remains unclear.AimsTo investigate the relationship between components of sarcopenia (muscle mass, handgrip strength, and gait speed) and components of osteoporosis [bone mass measured by bone mineral density (BMD) and bone microarchitecture measured by trabecular bone score (TBS)] in Chinese subjects.Methods318 Chinese men and 203 Chinese women were included in our study. Muscle mass and BMD were measured by dual-energy X-ray absorptiometry (DXA). TBS iNsight® software was used for TBS. Jamar hydraulic hand dynamometer was used to assess muscle strength, and gait speed was used to assess physical performance.ResultsWe found that the relative appendicular skeletal muscle mass (RASM) in both genders and handgrip strength in women correlated positively with TBS, RASM in men and handgrip strength in women correlated positively with BMDs. In the multiple linear regression model, RASM was positively associated with TBS in both genders, but no significant association was observed between RASM and BMDs. Interestingly, handgrip strength showed positive association with all evaluated BMDs and TBS in women, but not in men. Women with sarcopenia had lower TBS and BMDs at all evaluated sites. Men with sarcopenia had lower BMDs only at femur neck and total hip.ConclusionsThe reduction of muscle mass and strength was significantly associated with decreased bone mass and deteriorated bone microarchitecture. More importantly, low muscle mass is an independent risk factor for bone microarchitecture in Chinese subjects.
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