No abstract

a high-fat diet (HFd) or obesity-promoting diet is closely associated with metabolic diseases and intestinal tumors, particularly in middle-aged individuals (typically 45-64 years old). The intestinal epithelium constitutes a barrier that separates the host from the food and microbiota in the gut, and thus, a dysfunctional epithelium is associated with a number of diseases. However, the changes caused to the function of intestinal epithelium in response to an HFd have not been well-studied to date. in the present study, middle-aged female mice (12 months old) fed an HFd for a period of 14 weeks were used to determine the effects of HFd on the intestine. characteristics including the body weight, fat deposition, glucose metabolism, inflammatory state and intestinal morphology were assessed, while the intestinal stem cell (iSc) counts and the ability of isolated intestinal crypts to form organoid bodies in 3d culture were examined. intestinal epithelial barrier function, including secretory defense, tight junctions and cell apoptosis, were also studied. Morphologically, the HFd resulted in a mild reduction in the length of villi of the small intestine, the colon length and the depth of colon crypts. in addition, the iSc counts were increased in the small intestine and colon in HFd-fed mice. The ability of crypts to grow into organoids (mini-guts) was also increased in crypts obtained from mice fed an HFd, while HFd compromised the epithelial barrier function of the colon. These results demonstrated how an HFd affects the intestinal epithelium and highlighted the need to carefully consider dietary patterns.

Clinical evidence shows that visceral fat accumulation decreases whereas sc fat increases in patients treated with thiazolidinediones (TZDs), a type of peroxisome proliferator-activated receptor (PPAR)γ agonist. To clarify the molecular mechanism of the differential effects of PPARγ agonists on sc and visceral adipose, we investigated expression profiling of PPARγ-regulated micro-RNAs (miRNAs) using miRNA microarray. The level of 182 miRNAs changed in human sc adipose treated with pioglitazone, whereas only 46 miRNAs changed in visceral adipose. Among these miRNAs, 27 miRNAs changed in both human sc and visceral adipocytes. Specifically, 7 miRNAs changed at the same direction in sc and visceral adipocytes, whereas 20 miRNAs changed at opposite directions in these two fat depots. Bioinformatics analysis showed that these miRNAs and the predicted target genes were involved in TGF-β-, Wnt/β-catenin-, and insulin-signaling pathways and related to metabolic regulation or cell cycle. Among the miRNAs changed at the same direction in sc and visceral adipocytes, miR-378, located in the first intron of PPARγ coactivator 1β (PGC1β), was coordinately expressed with PGC1β during adipogenesis. Moreover, miR-378 and PGC1β were both up-regulated by PPARγ agonist. We also provided evidence that miR-378 promoted adipogenesis in sc fat, but not in visceral fat. These results display miRNAs expression profiling altered in sc and visceral adipogenesis regulated by PPARγ and suggest a potential mechanism underlying the differential effects of TZDs on the 2 fat depot accumulations.

ObjectiveWhether 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.DesignThe study has a cross-sectional design.SettingThe study was conducted in Jiangsu, China.ParticipantsA total of 101 men and 149 women aged 60 years or older were recruited.Outcome measuresLean 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).ResultsParticipants 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.ConclusionThe 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.

SummaryCalorie 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. C57BL/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.

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.

Physiological levels of glucocorticoids (GCs) are required for proper metabolic control, and excessive GC action has been linked to a variety of pandemic metabolic diseases. MicroRNA (miRNA)-19b plays a critical role in the pathogenesis of GC-induced metabolic diseases. This study explored the potential of miRNA-based therapeutics targeting adipose tissue. Our results showed that overexpressed miR-19b in stromal vascular fraction (SVF) cells derived from subcutaneous adipose tissue had the same effects as dexamethasone (DEX) treatment on the inhibition of adipose browning and oxygen consumption rate. The inhibition of miR-19b blocked DEX-mediated suppression of the expression of browning marker genes as well as the oxygen consumption rate in differentiated SVF cells derived from subcutaneous and brown adipose tissue. Overexpressed miR-19b in SVF cells derived from brown adipose tissue had the same effects as DEX treatment on the inhibition of brown adipose differentiation and energy expenditure. Glucocorticoids transcriptionally regulate the expression of miR-19b via a GC receptor-mediated direct DNA binding mechanism. This study confirmed that miR-19b is an essential target for GC-mediated control of adipose tissue browning. It is hoped that the plasticity of the adipose organ can be exploited in the next generation of therapeutic strategies to combat the increasing incidence of metabolic diseases, including obesity and diabetes.

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.