Correlation between serum advanced glycation end products and dietary intake of advanced glycation end products estimated from home cooking and food frequency questionnaires

Abstract Background & aims: To our knowledge the association between dietary advanced glycation end-products (dAGEs) and cardiometabolic disease is limited. Our aim was to examine the association between dAGEs and serum concentration of carboxymethyl-lysine (CML) or soluble receptor advanced glycation end-products (sRAGEs), and to assess the difference on dAGEs and circulating AGEs according to lifestyle and biochemical measures. Methods and results: 52 overweight or obese adults diagnosed with type 2 diabetes were included in this cross-sectional analysis. dAGEs were estimated from a Food Frequency Questionnaire (FFQ) or from a FFQ þ Home Cooking Frequency Questionnaire (HCFQ). Serum concentrations of CML and sRAGEs were measured by ELISA. Correlation tests were used to analyze the association between dAGEs derived from the FFQ or FFQ þ HCFQ and concentrations of CML or sRAGEs. Demographic characteristics, lifestyle factors and biochemical measures were analyzed according to sRAGEs and dAGEs using student t-test and ANCOVA. A significant inverse association was found between serum sRAGEs and dAGEs estimated using the FFQ þ HCFQ (r Z 0.36, p Z 0.010), whereas no association was found for dAGEs derived from the FFQ alone. No association was observed between CML and dAGEs. dAGEs intake estimated from the FFQ þ HCFQ was significantly higher among younger and male participants, and in those with higher BMI, higher Hb1Ac levels, longer time with type 2 diabetes, lower adherence to Mediterranean diet, and higher use of culinary techniques that generate more AGEs (all p values p < 0.05). Conclusions: These results show knowledge on culinary techniques is relevant to derive the association between dAGEs intake and cardiometabolic risk factors

Dietary Fat Intake and the Risk of Depression: The SUN Project

Emerging evidence relates some nutritional factors to depression risk. However, there is a scarcity of longitudinal assessments on this relationship. Objective: To evaluate the association between fatty acid intake or the use of culinary fats and depression incidence in a Mediterranean population. Material and Methods: Prospective cohort study (1999–2010) of 12,059 Spanish university graduates (mean age: 37.5 years) initially free of depression with permanently open enrolment. At baseline, a 136-item validated food frequency questionnaire was used to estimate the intake of fatty acids (saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), trans unsaturated fatty acids (TFA) and monounsaturated fatty acids (MUFA) and culinary fats (olive oil, seed oils, butter and margarine) During follow-up participants were classified as incident cases of depression if they reported a new clinical diagnosis of depression by a physician and/or initiated the use of antidepressant drugs. Cox regression models were used to calculate Hazard Ratios (HR) of incident depression and their 95% confidence intervals (CI) for successive quintiles of fats. Results: During follow-up (median: 6.1 years), 657 new cases of depression were identified. Multivariable-adjusted HR (95% CI) for depression incidence across successive quintiles of TFA intake were: 1 (ref), 1.08 (0.82–1.43), 1.17 (0.88–1.53), 1.28 (0.97–1.68), 1.42 (1.09–1.84) with a significant dose-response relationship (p for trend = 0.003). Results did not substantially change after adjusting for potential lifestyle or dietary confounders, including adherence to a Mediterranean Dietary Pattern. On the other hand, an inverse and significant dose-response relationship was obtained for MUFA (p for trend = 0.05) and PUFA (p for trend = 0.03) intake. Conclusions: A detrimental relationship was found between TFA intake and depression risk, whereas weak inverse associations were found for MUFA, PUFA and olive oil. These findings suggest that cardiovascular disease and depression may share some common nutritional determinants related to subtypes of fat intake

Correction to: Dimensions of leisure-time physical activity and risk of depression in the “Seguimiento Universidad de Navarra” (SUN) prospective cohort

After publication of our article [1] we have been notified that Table 2 was incorrectly formatte

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P &lt; 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Quaternary structure of a G-protein coupled receptor heterotetramer in complex with Gi and Gs

Background: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results: We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions: The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects