Differential Association of Glycation Products with Bone Mineral Density and Fat Mass in Healthy and Diabetes Type 2 Subjects from Mexican Southeastern: A Cross Sectional Study.

Background: Glycation products have been linked to decreased bone mineral density (BMD) in a number of clinical settings. This study examined the correlation between early glycation products (HbA1c and glycated albumin (ALB-g)) and advanced glycation end products (pentosidine (PTD)) with BMD in two groups of participants: those with type 2 diabetes mellitus (DM2) and those without diabetes or any other comorbidities (noDM). All of the participants had resided in southeastern Mexico for a minimum of 10 years. Material and Methods: This study included 204 participants: 112 (55%) with DM2 and 92 (45%) healthy subjects. We utilized dual X-ray absorptiometry (DXA) to measure both the total and segment-specific BMD and adipose mass. In addition, the fasting blood glucose, HbA1c, PTD, and ALB-g parameters were measured. Correlation and logistic regression analyses were conducted. Results: There was an inverse correlation between PTD and BMD in all anatomical regions among postmenopausal women (PMW) in the DM2 group, whereas in non-PMW, only the waist-to-height ratio was statistically significant. A negative correlation was observed between HbA1c levels and BMD in the arms and legs of DM2 individuals. However, in the noDM group, a negative correlation was found between HbA1c levels and BMD in the pelvis, while a positive association was observed between HbA1c and indicators of adipose tissue. ALB-g, demonstrated a negative correlation with fat mass. After performing binary logistic regressions, the following odds ratios (OR) for osteopenia/osteoporosis risk were determined: PTD OR 1.1 (p = 0.047) for DM2 PMW, HbA1c OR 1.4 (p = 0.048), and fat mass content OR 1.011 (p = 0.023) for the entire sample. Conclusions: Glycation products are associated with BMD differentially depending on the analyzed anatomical segment, but PTD, HbA1c, and fat mass are significant predictors of low bone mass. In prospective studies, this association could be determined using other techniques involving three-dimensional analysis of bone architecture to evaluate bone architecture.

c-Fos induction by gut hormones and extracellular ATP in osteoblastic-like cell lines.

It is widely accepted that the c-Fos gene has a role in proliferation and differentiation of bone cells. ATP-induced c-Fos activation is relevant to bone homeostasis, because nucleotides that are present in the environment of bone cells can contribute to autocrine/paracrine signalling. Gut hormones have previously been shown to have an effect on bone metabolism. In this study, we used the osteoblastic Saos-2 cell line transfected with a c-Fos-driven reporter stimulated with five gut hormones: glucose inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), ghrelin and obestatin, in the presence or absence of ATP. In addition, TE-85 cells were used to determine the time course of c-Fos transcript induction following stimulation with GLP-1, and GLP-2 with or without ATP, using reverse transcription qPCR. The significant results from the experiments are as follows: higher level of c-Fos induction in presence of GIP, obestatin (p = 0.019 and p = 0.011 respectively), and GIP combined with ATP (p < 0.001) using the luciferase assay; GLP-1 and GLP-2 combined with ATP (p = 0.034 and p = 0.002, respectively) and GLP-2 alone (p < 0.001) using qPCR. In conclusion, three of the gut peptides induced c-Fos, providing a potential mechanism underlying the actions of these hormones in bone which can be directed or enhanced by the presence of ATP.

Differential effects of adiponectin in osteoblast-like cells.

The skeleton should maintain an adequate volume, vigour and strength to carry out the role for which it is designed: to hold the whole soft tissue mass that shapes the body and to protect the vital organs. To fulfil this task a satisfactory food intake is required and regulators that are released in the feeding and fasting states, among other signals indicate how much soft mass needs to be built up. Those signals include the secretion of adipocytokines which could represent a relevant link between soft mass (adipose tissue) and skeleton. We studied the presence of adiponectin receptors (AdipoR1, AdipoR2) and its direct effects in osteosarcoma cell line Saos-2. The results indicated that adiponectin receptors were present in the osteoblastic cells with a higher expression of AdipoR1. Human recombinant globular adiponectin was able to increase viability levels and decrease cytotoxicity rates in cell cultures. Also, adiponectin significantly inhibited alkaline phosphatase activity in supernatants. Osteoprotegerin mRNA expression was significantly reduced after 72 h treatment. The FOS induction was studied and the results exhibited a significant increase caused by adiponectin. In conclusion, all these observations suggest that adiponectin influences bone metabolism decreasing the levels of bone formation. Regulators of adiponectin or its receptors could be circulating to modulate the activities of this peptide.

Potential effects of cannabidiol as a wake-promoting agent.

Over the last decades, the scientific interest in chemistry and pharmacology of cannabinoids has increased. Most attention has focused on ∆(9)-tetrahydrocannabinol (∆(9)-THC) as it is the psychoactive constituent of Cannabis sativa (C. sativa). However, in previous years, the focus of interest in the second plant constituent with non-psychotropic properties, cannabidiol (CBD) has been enhanced. Recently, several groups have investigated the pharmacological properties of CBD with significant findings; furthermore, this compound has raised promising pharmacological properties as a wake-inducing drug. In the current review, we will provide experimental evidence regarding the potential role of CBD as a wake-inducing drug.

Adiponectin receptors are present in RANK-L-induced multinucleated osteoclast-like cells.

Adiponectin is an adipokine that has been related to bone metabolism. Data on adiponectin receptors (AdipoR1, -R2) in osteoclasts have shown discrepancies. In this study we carried out observations of AdipoR1, -R2 in peripheral blood mononuclear cells that were induced to differentiate into osteoclasts. AdipoR1, -R2 were screened using reverse transcription and quantitative PCR and immunofluorescence. Acid phosphatase and Cathepsin-K were evaluated as osteoclastic markers. Results showed that acid phosphatase was expressed from day 1 whereas Cathepsin-K started from day 7. AdipoR1 and -R2 showed expression from day 1, with greater expression for AdipoR1 than AdipoR2. The immunofluorescent patterns were observed in the cells cultured under three different conditions: non-supplemented medium, added M-CSF, or medium with M-CSF, and RANK-L. The non-supplemented control did not display specific fluorescence whereas specific and strong signals were detected in cells cultured with combined M-CSF and RANK-L from day 7. The fluorescence patterns were detected mainly at the periphery of the cells, and in the cytoplasm, showing a localized patchy pattern for both receptors. In contrast, a diffuse fluorescent pattern was detected in the cytoplasm of the cells with M-CSF alone. In summary, AdipoR1 and -R2 were detected by quantitative PCR and immunofluorescence. The immunofluorescence patterns suggest that adiponectin receptors are located, or re-located, in the plasma membrane with distribution in the cytoplasm when mononuclear cells are committed to differentiate to osteoclasts. These findings could be a reasonable explanation for the controversy found in the published literature regarding the role of adiponectin in bone metabolism.

Association between fibromyalgia syndrome clinical severity and body composition. A principal component analysis.

INTRODUCTION: The type of body composition modulates the severity of some musculoskeletal conditions, in fibromyalgia syndrome (FMS), this type of association remains relatively unexplored. OBJECTIVE: To analyze the association between the type of body composition and FMS using Principal Component Analysis (PCA). The FMS clinical outcome measures were: Symptom Severity Scale (SSS), Widespread Pain Index (WPI; and Fibromyalgia Impact Questionnaire (FIQ). METHODS: Forty-three women with FMS (ACR 2010 criteria) were clinically and anthropometrically evaluated. The anthropometric data were integrated into two indicators using a PCA methodology (PCA-Fat and PCA-muscle). Additionally, the patients were classified into high and low categories for each clinical indicator, which were used as dependent variables in binomial logistic regression (BLR) models. RESULTS: We found a positive correlation between PCA-Fat with WPI (r=0.326, P=.043) and FIQ (r=0.325, P=.044), and negative correlation (r=-0.384, P=.013) between PCA-muscle and SSS. In the BLR analysis, PCA-Fat was a significant predictor for high WPI (OR=2.477, P=.038); while for high SSS, PCA-muscle (OR=0.303, P=.009) was an inversely significant predictor. CONCLUSIONS: The results suggest that the volume of fat mass can negatively modulate the severity of FMS. We propose that the evaluation of body composition should be a basic element for the clinical approach of patients with FMS.

Receptors and effects of gut hormones in three osteoblastic cell lines.

BACKGROUND: In recent years the interest on the relationship of gut hormones to bone processes has increased and represents one of the most interesting aspects in skeletal research. The proportion of bone mass to soft tissue is a relationship that seems to be controlled by delicate and subtle regulations that imply "cross-talks" between the nutrient intake and tissues like fat. Thus, recognition of the mechanisms that integrate a gastrointestinal-fat-bone axis and its application to several aspects of human health is vital for improving treatments related to bone diseases. This work analysed the effects of gut hormones in cell cultures of three osteoblastic cell lines which represent different stages in osteoblastic development. Also, this is the first time that there is a report on the direct effects of glucagon-like peptide 2, and obestatin on osteoblast-like cells. METHODS: mRNA expression levels of five gut hormone receptors (glucose-dependent insulinotropic peptide [GIP], glucagon-like peptide 1 [GLP-1], glucagon-like peptide 2 [GLP-2], ghrelin [GHR] and obestatin [OB]) were analysed in three osteoblastic cell lines (Saos-2, TE-85 and MG-63) showing different stages of osteoblast development using reverse transcription and real time polymerase chain reaction. The responses to the gut peptides were studied using assays for cell viability, and biochemical bone markers: alkaline phosphatase (ALP), procollagen type 1 amino-terminal propeptides (P1NP), and osteocalcin production. RESULTS: The gut hormone receptor mRNA displayed the highest levels for GIP in Saos-2 and the lowest levels in MG-63, whereas GHR and GPR39 (the putative obestatin receptor) expression was higher in TE-85 and MG-63 and lower in Saos-2. GLP-1 and GLP-2 were expressed only in MG-63 and TE-85. Treatment of gut hormones to cell lines showed differential responses: higher levels in cell viability in Saos-2 after GIP, in TE-85 and MG-63 after GLP-1, GLP-2, ghrelin and obestatin. ALP showed higher levels in Saos-2 after GIP, GHR and OB and in TE-85 after GHR. P1NP showed higher levels after GIP and OB in Saos-2. Decreased levels of P1NP were observed in TE-85 and MG-63 after GLP-1, GLP-2 and OB. MG-63 showed opposite responses in osteocalcin levels after GLP-2. CONCLUSIONS: These results suggest that osteoblast activity modulation varies according to different development stage under different nutrition related-peptides.

Evaluation of Anthropometric Indices and Lipid Parameters to Predict Metabolic Syndrome Among Adults in Mexico.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of conditions that increases the risk of cardiovascular disease (CVD) and is related to genetic background, dietary habits, and lifestyle. Anthropometric indices and lipid parameters have been shown to be simple and useful tools in clinical practice for predicting MetS. The aim of the present study was to evaluate the differential magnitudes of anthropometric characteristics (waist circumference and body mass index [BMI]) and lipid parameters, namely, lipid accumulation product (LAP), cardiometabolic index (CMI), and Castelli Risk Index (CRI-I), to estimate MetS, usingappropriate cut-off values, among adults from a public hospital in Yucatan, Mexico. METHODS: A cross-sectional study among 250 adults (77 men, 173 women) was carried out in the Regional High Speciality Hospital of the Yucatan Peninsula (HRAEPY) in Merida, Yucatan. MetS was diagnosed using standard criteria (central obesity, arterial hypertension, hyperglycemia, and dyslipidemia), and derived parameters (LAP, CMI, and CRI-I) were calculated. Binary logistic regression analysis-based receiver operating characteristics (ROC) curves were used to predict MetS. RESULTS: Of the 250 participants, 48% had MetS. High prevalences of overweight (35.2%) and obesity (48.8%) were found in the sample. The CMI and LAP were found to be the best parameters in the prediction of MetS in men and women. The optimal cut-off values of the parameters were higher in men and decreased with advancing age. CONCLUSION: The CMI and LAP were shown to be the most effective indicators to diagnose MetS among adults from Yucatan, Mexico.

Association between Overweight/Obesity and Clinical Activity in Rheumatoid Arthritis. / Asociación entre sobrepeso/obesidad y estado clínico en artritis reumatoide.

INTRODUCTION: The effect of overweight/obesity on clinical status in rheumatoid arthritis (RA) is still a controversial topic. AIM: To assess the association between body composition and clinical status in RA patients. METHODS: A prospective, comparative, cross-sectional study was performed on 123 (98.4% women, 86.3% FR+, 9.3±8.7 duration years) RA patients diagnosed according to ACR/EULAR 2010 criteria who were assessed for inflammatory activity (DAS 28), functional status (HAQ-Di), and type of treatment. Body composition was evaluated by BMI, waist, hip, and middle arm girths, waist/hip ratio, skin fold measurements, and bioelectrical impedance analysis. RESULTS: The prevalence of overweight and obesity (BMI-WHO cut-off points) was 30.9% and 45.5% respectively. Using Stavropoulos-Kalinoglou cut-off points, each corresponding prevalence increased to 31.7% and 58.5%, respectively. Pooled patients in the overweight/obesity classification (Stavropoulos-Kalinoglou classification) exhibited a significantly higher number of swollen joints as compared to subnormal/normal body composition subjects (3.8±3.3 vs. 1.9±2.5; p=.02). Swollen joint count showed significant positive correlation with 6 out of 11 body composition parameters: BMI; arm and hip girths, triceps skin fold, body fat average determined by bioelectrical impedance analysis, and skin fold measurements. CONCLUSIONS: Prevalence of obesity in RA varies according to BMI cut-off points. Overweight and obesity were associated with higher inflammatory activity characterized by a higher count of tender and swollen joints. A positive correlation was found between swollen joint amount and the majority of the body fat mass indicators assessed. Body composition assessment/improvement should be an important part of the routine care of RA patients.

Smoking index, lifestyle factors, and genomic instability assessed by single-cell gel electrophoresis: a cross-sectional study in subjects from Yucatan, Mexico.

BACKGROUND: It is widely accepted that genomic instability is associated with several mechanisms involving oxidative stress, which can increase the rate of DNA breaks. Such factors include smoking, impairments in body composition, an unhealthy lifestyle, and a hereditary history of cancer. The aim was to evaluate the degree of association of genomic instability in smokers and non-smokers, and how the risk could change depending on the lifestyle and other causes. For this purpose, a survey of tobacco consumption, dietary patterns, physical activity, antecedents of cancer, and body composition assessment was carried out. Genomic instability was evaluated through a single-cell gel electrophoresis using peripheral blood mononuclear cells in three different conditions of oxidative stress. The analysis of genomic damage degree was performed through a dimension reduction procedure (principal component analysis) from 16 parameters per treatment (adding up 48 parameters of genomic damage per subject) and a binary logistic regression model for DNA fragmentation risk. RESULTS: The sample consisted of 82 participants, divided into three age groups: young adults (18-35 years), adults (36-59 years), and older adults (60-95 years). As expected, the results showed a significant positive correlation of age with genomic damage rates, represented by 2 PCA groups (p = 0.027, p = 0.004). There were consistent significant positive associations of genomic damage rates with smoking index and three PCA groups (p = 0.007, p = 0.004, p = 0.009). The smoking status and age group analysis revealed that there were significant differences for adult smokers with the same aforementioned PCA groups (p = 0.002, p = 0.001, p = 0.010). In addition, higher DNA damage rates were found in subjects with incorrect diet patterns, long sitting hours, and previous exposure to radiation. The analysis with binary logistic regression displayed two models in which lifestyles (age, diet, and/or sedentarism) did not change the significance of smoking index for DNA fragmentation risk; however, when physical activity was present in the model, the smoking index was not a significant factor for DNA damage risk. CONCLUSIONS: Although it is well known that smoking affects human health in different ways, DNA fragmentation can be analyzed by a damage phenotypic analysis and integrate a risk analysis reshaped by diet and lifestyle in general.

Association between body composition and disease activity in rheumatoid arthritis. A systematic review. / Asociación entre composición corporal y actividad inflamatoria en artritis reumatoide. Una revisión sistemática.

BACKGROUND: Reports regarding the association between body composition and inflammatory activity in rheumatoid arthritis (RA) have consistently yielded contradictory results. OBJECTIVE: To perform a systematic review on the association between overweight/obesity and inflammatory activity in RA. METHODS: FAST approach: Article search (Medline, EBSCO, Cochrane Library), followed by abstract retrieval, full text review and blinded assessment of methodological quality for final inclusion. Because of marked heterogeneity in statistical approach and RA activity assessment method, a meta-analysis could not be done. Results are presented as qualitative synthesis. RESULTS: One hundred and nineteen reports were found, 16 of them qualified for full text review. Eleven studies (8,147 patients; n range: 37-5,161) approved the methodological quality filter and were finally included. Interobserver agreement for methodological quality score (ICC: 0.93; 95% CI: 0.82-0.98; P<.001) and inclusion/rejection decision (k 1.00, P>.001) was excellent. In all reports body composition was assessed by BMI; however a marked heterogeneity was found in the method used for RA activity assessment. A significant association between BMI and RA activity was found in 6 reports having larger mean sample size: 1,274 (range: 140-5,161). On the other hand, this association was not found in 5 studies having lower mean sample size: 100 (range: 7-150). CONCLUSIONS: The modulation of RA clinical status by body fat mass is suggested because a significant association was found between BMI and inflammatory activity in those reports with a trend toward higher statistical power. The relationship between body composition and clinical activity in RA requires be approached with further studies with higher methodological quality.

Characterization of Mitogen-Activated Protein Kinase Expression in Nucleus Accumbens and Hippocampus of Rats Subjected to Food Selection in the Cafeteria Diet Protocol.

Obesity is a world-wide health problem that requires different experimental perspectives to understand the onset of this disease, including the neurobiological basis of food selection. From a molecular perspective, obesity has been related with activity of several endogenous molecules, including the mitogenactivated protein kinases (MAP-K). The aim of this study was to characterize MAP-K expression in hedonic and learning and memory brain-associated areas such as nucleus accumbens (AcbC) and hippocampus (HIPP) after food selection. We show that animals fed with cafeteria diet during 14 days displayed an increase in p38 MAP-K activity in AcbC if chose cheese. Conversely, a diminution was observed in animals that preferred chocolate in AcbC. Also, a decrease of p38 MAP-K phosphorylation was found in HIPP in rats that selected either cheese or chocolate. Our data demonstrate a putative role of MAP-K expression in food selection. These findings advance our understanding of neuromolecular basis engaged in obesity.

Intrahypothalamic Administration of Modafinil Increases Expression of MAP-Kinase in Hypothalamus and Pons in Rats.

Modafinil (MOD) it has to be considered as a wake-inducing drug to treat sleep disorders such as excessive sleepiness in narcolepsy, shift-work disorder, and obstructive/sleep apnea syndrome. Current evidence suggests that MOD induces waking involving the dopamine D1 receptor. However, little is known regarding the molecular elements linked in the wake-promoting actions of MOD. Since the D1 receptor activates the mitogen-activated protein kinase (MAP-K) cascade, it raises the interesting possibility that effects of MOD would depend upon the activation of MAP-K. Here we tested the expression of MAP-K in hypothalamus as well as pons after the microinjection of MOD (10 or 20 µg/1 µL) in rats into anterior hypothalamus, a wake-inducing brain area. Intrahypothalamic injections of MOD promoted MAP-K phosphorylation in hypothalamus and pons. Taken together, these results suggest that the wake-inducing compound MOD promotes the MAP-K phosphorylation.

The emerging role of the endocannabinoid system in the sleep-wake cycle modulation.

The endocannabinoid system comprises amides, esters and ethers of long chain polyunsaturated fatty acids. Narachidonoylethanolamide (anandamide; ANA) and 2-arachidonoylglycerol (2-AG) are endogenous cannabinoids (endocannabinoids) ligands for the cannabinoid family of G-protein-coupled receptors named CB1 and CB2. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and behave as retrograde signaling messengers, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters systems. The two principal enzymes that are responsible for the metabolism of ANA and 2-AG are fatty acid amide hydrolase and monoacylglycerol lipase, respectively. Pharmacological experiments have shown that the administration of endocannabinoids induce cannabimimetic effects, including sleep promotion. This review will focus on some of the current evidence of the pharmacological potential of the endocannabinoid system on sleep modulation.