| 1. |
- Barbarroja, Nuria, et al.
(författare)
-
Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function
- 2015
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:4, s. 1180-1192
-
Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue dysfunction is an important determinant of obesity-associated, lipid-induced metabolic complications. Ceramides are well-known mediators of lipid-induced insulin resistance in peripheral organs such as muscle. DEGS1 is the desaturase catalyzing the last step in the main ceramide biosynthetic pathway. Functional suppression of DEGS1 activity results in substantial changes in ceramide species likely to affect fundamental biological functions such as oxidative stress, cell survival, and proliferation. Here, we show that degs1 expression is specifically decreased in the adipose tissue of obese patients and murine models of genetic and nutritional obesity. Moreover, loss-of-function experiments using pharmacological or genetic ablation of DEGS1 in preadipocytes prevented adipogenesis and decreased lipid accumulation. This was associated with elevated oxidative stress, cellular death, and blockage of the cell cycle. These effects were coupled with increased dihydroceramide content. Finally, we validated in vivo that pharmacological inhibition of DEGS1 impairs adipocyte differentiation. These data identify DEGS1 as a new potential target to restore adipose tissue function and prevent obesity-associated metabolic disturbances.
|
|
| 2. |
- Delgado-Lista, Javier, et al.
(författare)
-
Top Single Nucleotide Polymorphisms Affecting Carbohydrate Metabolism in Metabolic Syndrome : From the LIPGENE Study
- 2014
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 99:2, s. E384-E389
-
Tidskriftsartikel (refereegranskat)abstract
- Rationale: Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Objectives: Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. Methods: A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. Findings: From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). Conclusions: We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.
|
|
| 3. |
- Perez-Martinez, Pablo, et al.
(författare)
-
Gene-nutrient interactions on the phosphoenolpyruvate carboxykinase influence insulin sensitivity in metabolic syndrome subjects
- 2013
-
Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 32:4, s. 630-635
-
Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Genetic background may interact with habitual dietary fat composition, and affect development of the metabolic syndrome (MetS). The phosphoenolpyruvate carboxykinase gene (PCK1) plays a significant role regulating glucose metabolism, and fatty acids are key metabolic regulators, which interact with transcription factors and influence glucose metabolism. We explored genetic variability at the PCK1 gene locus in relation to degree of insulin resistance and plasma fatty acid levels in MetS subjects. Moreover, we analyzed the PCK1 gene expression in the adipose tissue of a subgroup of MetS subjects according to the PCK1 genetic variants. Methods: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma concentrations of C-peptide, fatty acid composition and three PCK1 tag-single nucleotide polymorphisms (SNPs) were determined in 443 MetS participants in the UPGENE cohort. Results: The rs2179706 SNP interacted with plasma concentration of n - 3 polyunsaturated fatty acids (n - 3 PUFA), which were significantly associated with plasma concentrations of fasting insulin, peptide C, and HOMA-IR. Among subjects with n - 3 PUFA levels above the population median, carriers of the C/C genotype exhibited lower plasma concentrations of fasting insulin (P = 0.036) and HOMA-IR (P = 0.019) as compared with C/C carriers with n - 3 PUFA below the median. Moreover, homozygous C/C subjects with n - 3 PUFA levels above the median showed lower plasma concentrations of peptide C as compared to individuals with the T-allele (P = 0.006). Subjects carrying the T-allele showed a lower gene PCK1 expression as compared with carriers of the C/C genotype (P = 0.015). Conclusions: The PCK1 rs2179706 polymorphism interacts with plasma concentration of n - 3 PUFA levels modulating insulin resistance in MetS subjects.
|
|
| 4. |
- Tavares, Julia, et al.
(författare)
-
Basin-wide variation in tree hydraulic safety margins predicts the carbon balance of Amazon forests
- 2023
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 617:7959, s. 111-117
-
Tidskriftsartikel (refereegranskat)abstract
- Tropical forests face increasing climate risk(1,2), yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, ?(50)) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk(3-5), little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters ?(50) and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both ?(50) and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM(50 )forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon(6,7), with strong implications for the Amazon carbon sink.
|
|
| 5. |
- Belyaev, Alexander S., et al.
(författare)
-
A to Z of the muon anomalous magnetic moment in the MSSM with Pati-Salam at the GUT scale
- 2016
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2016:6
-
Tidskriftsartikel (refereegranskat)abstract
- We analyse the low energy predictions of the minimal supersymmetric standard model (MSSM) arising from a GUT scale Pati-Salam gauge group further constrained by an A4 × Z5 family symmetry, resulting in four soft scalar masses at the GUT scale: one left-handed soft mass m0 and three right-handed soft masses m1, m2, m3, one for each generation. We demonstrate that this model, which was initially developed to describe the neutrino sector, can explain collider and non-collider measurements such as the dark matter relic density, the Higgs boson mass and, in particular, the anomalous magnetic moment of the muon (g − 2)μ. Since about two decades, (g − 2)μ suffers a puzzling about 3σ excessoftheexperimentallymeasuredvalueoverthetheoreticalprediction,whichour model is able to fully resolve. As the consequence of this resolution, our model predicts specific regions of the parameter space with the specific properties including light smuons and neutralinos, which could also potentially explain di-lepton excesses observed by CMS and ATLAS.
|
|
| 6. |
- Camargo-Molina, José Eliel, et al.
(författare)
-
All one-loop scalar vertices in the effective potential approach
- 2016
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2016:8
-
Tidskriftsartikel (refereegranskat)abstract
- Using the one-loop Coleman-Weinberg effective potential, we derive a general analytic expression for all the derivatives of the effective potential with respect to any number of classical scalar fields. The result is valid for a renormalisable theory in four dimensions with any number of scalars, fermions or gauge bosons. This result corresponds to the zero-external momentum contribution to a general one-loop diagram with N scalar external legs. We illustrate the use of the general result in two simple scalar singlet extensions of the Standard Model, to obtain the dominant contributions to the triple couplings of light scalar particles under the zero external momentum approximation.
|
|
| 7. |
- Camargo-Molina, José Eliel, et al.
(författare)
-
On a radiative origin of the Standard Model from trinification
- 2016
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; 2016:9
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, we present a trinification-based grand unified theory incorporating a global SU(3) family symmetry that after a spontaneous breaking leads to a left-right symmetric model. Already at the classical level, this model can accommodate the matter content and the quark Cabbibo mixing in the Standard Model (SM) with only one Yukawa coupling at the unification scale. Considering the minimal low-energy scenario with the least amount of light states, we show that the resulting effective theory enables dynamical breaking of its gauge group down to that of the SM by means of radiative corrections accounted for by the renormalisation group evolution at one loop. This result paves the way for a consistent explanation of the SM breaking scale and fermion mass hierarchies.
|
|
| 8. |
- Camargo-Molina, José Eliel, et al.
(författare)
-
On a radiative origin of the standard model in non-supersymmetric trinification with global SU(3)F
- 2016
-
Ingår i: Proceedings of Science. - 1824-8039. ; Part F128560
-
Tidskriftsartikel (refereegranskat)abstract
- We present a trinification-based grand unified theory incorporating a global SU(3)F family symmetry, that after spontaneous symmetry breaking leads to a left-right symmetric model. In addition to unification of gauge couplings, the model unifies Yukawa interactions and contains equivalent representations in the scalar and fermion sectors at high energy scales. Considering the minimal low-energy scenario with the least amount of light states, we show that the resulting effective theory enables dynamical breaking of its gauge group to that of the Standard Model by means of radiative corrections accounted for by the renormalisation group evolution at leading order. This result paves the way for a possible explanation of the SM breaking scale and fermion mass hierarchies.
|
|
| 9. |
- Camargo-Molina, José E., et al.
(författare)
-
Reviving trinification models through an E6 -extended supersymmetric GUT
- 2017
-
Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 2470-0010. ; 95:7
-
Tidskriftsartikel (refereegranskat)abstract
- We present a supersymmetric (SUSY) model based on trinification [SU(3)]3 and family SU(3)F symmetries embedded into a maximal subgroup of E8, where the sectors of light Higgs bosons and leptons are unified into a single chiral supermultiplet. The common origin of gauge trinification and of the family symmetry from E8 separates the model from other trinification-based GUTs, as it protects, in particular, the Standard Model fermions from gaining mass until the electroweak symmetry is broken. Furthermore, it allows us to break the trinification symmetry via vacuum expectation values in SU(3)-adjoint scalars down to a left-right symmetric theory. Simultaneously, it ensures the unification of the gauge and Yukawa couplings as well as proton stability. Although the low-energy regime (e.g., mass hierarchies in the scalar sector determined by a soft SUSY-breaking mechanism) is yet to be established, these features are one key to revive the once very popular trinification-based GUTs.
|
|
| 10. |
- Camargo-Molina, José E., et al.
(författare)
-
Scale hierarchies, symmetry breaking, and particle spectra in SU(3)-family extended SUSY trinification
- 2019
-
Ingår i: Physical Review D. - 2470-0010. ; 99:3
-
Tidskriftsartikel (refereegranskat)abstract
- A unification of left-right SU(3)L×SU(3)R, color SU(3)C, and family SU(3)F symmetries in a maximal rank-8 subgroup of E8 is proposed as a landmark for future explorations beyond the Standard Model (SM). We discuss the implications of this scheme in a supersymmetric (SUSY) model based on the trinification gauge [SU(3)]3 and global SU(3)F-family symmetries. Among the key properties of this model are the unification of SM Higgs and lepton sectors, a common Yukawa coupling for chiral fermions, the absence of the μ problem, gauge couplings unification, and proton stability to all orders in perturbation theory. The minimal field content consistent with a SM-like effective theory at low energies is composed of one E6 27-plet per generation as well as three gauge and one family SU(3) octets inspired by the fundamental sector of E8. The details of the corresponding (SUSY and gauge) symmetry-breaking scheme, multiscale gauge couplings' evolution, and resulting effective low-energy scenarios are discussed.
|
|
