Systematic metabolomic studies identified adult adiposity biomarkers with acetylglycine associated with fat loss in vivo.

Obesity is associated with various adverse health outcomes. Body fat (BF) distribution is recognized as an important factor of negative health consequences of obesity. Although metabolomics studies, mainly focused on body mass index (BMI) and waist circumference, have explored the biological mechanisms involved in the development of obesity, these proxy composite measures are not accurate and cannot reflect BF distribution, and thus may hinder accurate assessment of metabolic alterations and differential risk of metabolic disorders among individuals presenting adiposity differently throughout the body. Thus, the exact relations between metabolites and BF remain to be elucidated. Here, we aim to examine the associations of metabolites and metabolic pathways with BF traits which reflect BF distribution. We performed systematic untargeted serum metabolite profiling and dual-energy X-ray absorptiometry (DXA) whole body fat scan for 517 Chinese women. We jointly analyzed DXA-derived four BF phenotypes to detect cross-phenotype metabolite associations and to prioritize important metabolomic factors. Topology-based pathway analysis was used to identify important BF-related biological processes. Finally, we explored the relationships of the identified BF-related candidate metabolites with BF traits in different sex and ethnicity through two independent cohorts. Acetylglycine, the top distinguished finding, was validated for its obesity resistance effect through in vivo studies of various diet-induced obese (DIO) mice. Eighteen metabolites and fourteen pathways were discovered to be associated with BF phenotypes. Six of the metabolites were validated in varying sex and ethnicity. The obesity-resistant effects of acetylglycine were observed to be highly robust and generalizable in both human and DIO mice. These findings demonstrate the importance of metabolites associated with BF distribution patterns and several biological pathways that may contribute to obesity and obesity-related disease etiology, prevention, and intervention. Acetylglycine is highlighted as a potential therapeutic candidate for preventing excessive adiposity in future studies.

Identification of PDXDC1 as a novel pleiotropic susceptibility locus shared between lumbar spine bone mineral density and birth weight.

An increasing number of epidemiological studies have suggested that birth weight (BW) may be a determinant of bone health later in life, although the underlying genetic mechanism remains unclear. Here, we applied a pleiotropic conditional false discovery rate (cFDR) approach to the genome-wide association study (GWAS) summary statistics for lumbar spine bone mineral density (LS BMD) and BW, aiming to identify novel susceptibility variants shared between these two traits. We detected 5 novel potential pleiotropic loci which are located at or near 7 different genes (NTAN1, PDXDC1, CACNA1G, JAG1, FAT1P1, CCDC170, ESR1), among which PDXDC1 and FAT1P1 have not previously been linked to these phenotypes. To partially validate the findings, we demonstrated that the expression of PDXDC1 was dramatically reduced in ovariectomized (OVX) mice in comparison with sham-operated (SHAM) mice in both the growth plate and trabecula bone. Furthermore, immunohistochemistry assay with serial sections showed that both osteoclasts and osteoblasts express PDXDC1, supporting its potential role in bone metabolism. In conclusion, our study provides insights into some shared genetic mechanisms for BMD and BW as well as a novel potential therapeutic target for the prevention of OP in the early stages of the disease development. KEY MESSAGES : We investigated pleiotropy-informed enrichment between LS BMD and BW. We identified genetic variants related to both LS BMD and BW by utilizing a cFDR approach. PDXDC1 is a novel pleiotropic gene which may be related to both LS BMD and BW. Elevated expression of PDXDC1 is related to higher BMD and lower ratio n-6/n-3 PUFA indicating a bone protective effect of PDXDC1.

Observation of the effect of one-to-one education on high-risk cases of diabetic foot.

BACKGROUND: Diabetes is a common chronic disease, and its global incidence is on the rise. The disease is directly attributed to insufficient insulin efficacy/secretion, and patients are often accompanied by multiple complications. Diabetic foot is one of the most common complications of diabetes. Diabetic feet have ulcers and infections, which can eventually lead to amputation. Basic nursing care, such as lowering blood pressure and preventing foot skin infections in clinical nursing work, has positive significance for the prevention and control of diabetic feet. AIM: To explore the positive significance of one-to-one education in high-risk cases of diabetic foot. METHODS: This observation included 98 high-risk cases of diabetic foot in our hospital during the period from August 2017 to October 2019, and these patients were randomly divided into the basic nursing group and the one-to-one education group with 49 patients per group. The basic nursing group only received routine basic nursing, while the one-to-one education group gave patients one-to-one education on the basis of basic nursing. After nursing, the self-care ability and compliance behavior of the two groups were evaluated and compared between these two groups. The knowledge mastery of the patient and the satisfaction of nursing were accounted. RESULTS: The assessment results of patients (self-care responsibility, self-care skills, self-concept and self-care knowledge) were significantly higher in the one-to-one education group than in the basic nursing group. The scores of compliance behaviors (foot bathing, shoes and socks selection, sports health care) in the one-to-one education group were significantly higher than those in the basic nursing group. Patients in the one-to-one education group had a significantly higher level of knowledge mastery and satisfaction of nursing than the basic nursing group. CONCLUSION: One-to-one education for high-risk cases of diabetic foot is helpful to improve the cognition and self-care ability of patients with diabetic foot, to ensure that patients follow the doctor's advice of self-care and to improve their nursing satisfaction.

Enhanced Identification of Novel Potential Variants for Appendicular Lean Mass by Leveraging Pleiotropy With Bone Mineral Density.

Strong relationships have been found between appendicular lean mass (ALM) and bone mineral density (BMD). It may be due to a shared genetic basis, termed pleiotropy. By leveraging the pleiotropy with BMD, the aim of this study was to detect more potential genetic variants for ALM. Using the conditional false discovery rate (cFDR) methodology, a combined analysis of the summary statistics of two large independent genome wide association studies (GWAS) of ALM (n = 73,420) and BMD (n = 10,414) was conducted. Strong pleiotropic enrichment and 26 novel potential pleiotropic SNPs were found for ALM and BMD. We identified 156 SNPs for ALM (cFDR <0.05), of which 74 were replicates of previous GWASs and 82 were novel SNPs potentially-associated with ALM. Eleven genes annotated by 31 novel SNPs (13 pleiotropic and 18 ALM specific) were partially validated in a gene expression assay. Functional enrichment analysis indicated that genes corresponding to the novel potential SNPs were enriched in GO terms and/or KEGG pathways that played important roles in muscle development and/or BMD metabolism (adjP <0.05). In protein-protein interaction analysis, rich interactions were demonstrated among the proteins produced by the corresponding genes. In conclusion, the present study, as in other recent studies we have conducted, demonstrated superior efficiency and reliability of the cFDR methodology for enhanced detection of trait-associated genetic variants. Our findings shed novel insight into the genetic variability of ALM in addition to the shared genetic basis underlying ALM and BMD.

Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women.

CONTEXT: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. OBJECTIVE: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. DESIGN AND METHODS: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. RESULTS: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 µM). CONCLUSIONS: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

[A novel method for quantitative measurement of orbital fat volume based on magnetic resonance images].

OBJECTIVE: To establish a new method for rapid and quantitative measurement of orbital fat volume based on magnetic resonance imaging (MRI) data. METHODS: We collected MRI data from normalized mold and patients with the diagnosis of thyroid-associated ophthalmopathy (TAO). The cross-sectional areas of the orbital fat on each MR image slice were measured to calculate the fat volume on each slice and then the total orbital fat volume. We recorded the time for completing the measurement and assessed the precision, reliability, repeatability and interoperator variations of the results. RESULTS: This MRI data-based method allowed precise measurement of the orbital fat volumes with an absolute value of the mean percentage difference <1%. This method was fast and the results showed a good repeatability (with CVs <1%), a high reliability (ICC=0.996, 95%CI: 0.985-0.999) and a high interoperator concordance (95%CI of the Bland-Altman: -0.54-0.90). CONCLUSION: The novel method we established for orbital fat volume measurement is rapid, accurate, reliable and reproducible with a low learning cost for clinical use.

[Calculation of orbital fat volumes for determining treatment timing for thyroid- associated ophthalmopathy].

OBJECTIVE: To analyze the relationship between orbital fat volume and the progression and prognosis of thyroid- associated ophthalmopathy (TAO) and determine the optimal treatment timing for TAO. METHODS: The clinical data were collected from 35 patients (70 orbits) with a definite diagnosis of TAO between January, 2016 and December, 2016. The correlation between orbital fat volume and the clinical parameters was evaluated. We also analyzed the correlation of the signal intensity ratio (SIR) of the extraocular muscles with the clinical parameters. The orbital fat volume was compared between patients with TAO and 12 control subjects. RESULTS: The orbital fat volume was significantly correlated with the duration of TAO (r=0.480, P<0.01), but showed no significant difference between patients with a disease course within 6 months and those with a disease course of 6 to 12 months (P=0.084). The patients with a disease course beyond 12 months had a significantly greater orbital fat volume than those with a disease course of 6 months (P<0.01) or 6 to 12 months (P<0.05). The orbital fat volume was correlated with the degree of proptosis (r=0.622, P<0.01), and an increase of exophthalmos by 1 mm was associated with a total orbital volume increment of 0.88 mL. The clinical activity score was correlated with the SIR of the extraorbital muscles (r=0.536, P<0.01) and levels of anti-thyroid-stimulating hormone receptor antibody (r=0.416,P<0.01). The orbital fat volume was significantly greater in TAO patients than in the healthy individuals (P<0.01). CONCLUSION: In patients with TAO, the peak increase of orbital fat volume occurs one year after the disease onset. Measurement of the orbital fat volume combined with SIR of the extraorbital muscles can serve as an indicator for determining the optimal timing for intervention of TAO and helps in the evaluation of prognosis of the patients.