Is skeletal muscle mitochondrial dysfunction a cause or an indirect consequence of insulin resistance in humans?

The precise cause of insulin resistance and type 2 diabetes is unknown. However, there is a strong association between insulin resistance and lipid accumulation — and, in particular, lipotoxic fatty acid metabolites — in insulin-target tissues. Such accumulation is known to cause insulin resistance, particularly in skeletal muscle, by reducing insulin-stimulated glucose uptake. Reduced fat-oxidation capacity appears to cause such lipid accumulation and, over the past few years, many studies have concluded that decreased mitochondrial oxidative phosphorylation could be the initiating cause of lipid deposition and the development of insulin resistance. The aim of this review is to summarize the latest findings regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance in humans. At present, there are too few studies to definitively conclude that, in this context, mitochondria are functionally impaired (dysfunction in the respiratory chain). Indeed, insulin resistance could also be related to a decrease in the number of mitochondria or to a combination of this and mitochondrial dysfunction. Finally, we also consider whether or not these aberrations could be the cause of the development of the disease or whether mitochondrial dysfunction may simply be the consequence of an insulin-resistant state

Thyroxine Therapy in Euthyroid Patients Does Not Affect Body Composition or Muscular Function

OBJECTIVE:The main objective of the study was to evaluate the effects of small increments in thyroxine (T4) levels following levothyroxine (L-T4) administration on the body composition of women patients. The secondary objective was to assess the effect of the therapy on energy expenditure and muscular function. METHODS: The prospective, randomized study consisted of a 12-month follow-up of 37 women with thyroid nodules. The patients were divided into two groups for comparison, one treated with L-T4 (20 women) and the other untreated (17 women). L-T4 dose was individually adjusted to obtain a serum thyroid-stimulating hormone in the lower portion of the normal range. Multiple tests, including bioelectrical impedance analysis, dual-energy X-ray absorptiometry, air displacement plethysmography, measurement of waist circumference, and skinfold anthropometry, were used to investigate the muscular, fat, and water compartments; energy expenditure and muscular function were assessed by cycle ergometry. RESULTS: There were no significant differences in body composition, heart rate, energy metabolism, or muscular function between the group of women treated with L-T4 and the untreated group. CONCLUSION: The controlled increase of circulating T4 does not appear to modify the body composition or muscular function in women patients

Erratum. Maternal ageing impairs mitochondrial DNA kinetics during early embryogenesis in mice

STUDY QUESTION: Does ageing affect the kinetics of the mitochondrial pool during oogenesis and early embryogenesis? SUMMARY ANSWER: While we found no age-related change during oogenesis, the kinetics of mitochondrial DNA content and the expression of the factors involved in mitochondrial biogenesis appeared to be significantly altered during embryogenesis. WHAT IS KNOWN ALREADY: Oocyte mitochondria are necessary for embryonic development. The morphological and functional alterations of mitochondria, as well as the qualitative and quantitative mtDNA anomalies, observed during ovarian ageing may be responsible for the alteration of oocyte competence and embryonic development. STUDY DESIGN, SIZE, DURATION: The study, conducted from November 2016 to November 2017, used 40 mice aged 5-8 weeks and 45 mice aged 9-11 months (C57Bl6/CBA F(1)). A total of 488 immature oocytes, with a diameter ranging from 20 μm to more than 80 μm, were collected from ovaries, and 1088 mature oocytes or embryos at different developmental stages (two PN, one-cell, i.e. syngamy, two-cell, four-cell, eight-cell, morula and blastocyst) were obtained after ovarian stimulation and, for embryos, mating. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mitochondrial DNA was quantified by quantitative PCR. We used quantitative reverse transcriptase PCR (RT-PCR) (microfluidic method) to study the relative expression of three genes involved in the key steps of embryogenesis, i.e. embryonic genome activation (HSPA1) and differentiation (CDX2 and NANOG), two mtDNA genes (CYB and ND2) and five genes essential for mitochondrial biogenesis (PPARGC1A, NRF1, POLG, TFAM and PRKAA). The statistical analysis was based on mixed linear regression models applying a logistic link function (STATA v13.1 software), with values of P < 0.05 being considered significant. MAIN RESULTS AND THE ROLE OF CHANCE: During oogenesis, there was a significant increase in oocyte mtDNA content (P < 0.0001) without any difference between the two groups of mice (P = 0.73). During the first phase of embryogenesis, i.e. up to the two-cell stage, embryonic mtDNA decreased significantly in the aged mice (P < 0.0001), whereas it was stable for young mice (young/old difference P = 0.015). The second phase of embryogenesis, i.e. between the two-cell and eight-cell stages, was characterized by a decrease in embryonic mtDNA for young mice (P = 0.013) only (young/old difference P = 0.038). During the third phase, i.e. between the eight-cell and blastocyst stage, there was a significant increase in embryonic mtDNA content in young mice (P < 0.0001) but not found in aged mice (young/old difference P = 0.002). We also noted a faster expression of CDX2 and NANOG in the aged mice than in the young mice during the second (P = 0.007 and P = 0.02, respectively) and the third phase (P = 0.01 and P = 0.008, respectively) of embryogenesis. The expression of mitochondrial genes CYB and ND2 followed similar kinetics and was equivalent for both groups of mice, with a significant increase during the third phase (P < 0.01). Of the five genes involved in mitochondrial biogenesis, i.e. PPARGC1A, NRF1, POLG, TFAM and PRKAA, the expression of three genes decreased significantly during the first phase only in young mice (NRF1, P = 0.018; POLGA, P = 0.002; PRKAA, P = 0.010), with no subsequent difference compared to old mice. In conclusion, during early embryogenesis in the old mice, we suspect that the lack of a replicatory burst before the two-cell stage, associated with the early arrival at the minimum threshold value of mtDNA, together with the absence of an increase of mtDNA during the last phase, might potentially deregulate the key stages of early embryogenesis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Because of the ethical impossibility of working on a human, this study was conducted only on a murine model. As superovulation was used, we cannot totally exclude that the differences observed were, at least partially, influenced by differences in ovarian response between young and old mice. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest a pathophysiological explanation for the link observed between mitochondria and the deterioration of oocyte quality and early embryonic development with age. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the University of Angers, France, by the French national research centres INSERM and the CNRS and, in part, by PHASE Division, INRA. There are no competing interests

The mitochondrial DNA content of cumulus cells may help predict embryo implantation

PURPOSE: The quantification of mtDNA in cumulus granulosa cells (CGCs) surrounding an oocyte has been positively linked with morphological embryonic quality. In the present study, we evaluated the link between the amount of mtDNA in CGCs surrounding an oocyte and the chances for the corresponding embryo of implanting and leading to an ongoing pregnancy. METHODS: This is an observational study, performed on 84 oocyte-cumulus-complexes (OCCs) having led to the replacement of an embryo in the maternal uterus, retrieved from 71 patients undergoing IVF with intracytoplasmic sperm. The OCCs were classified in two groups, one including 26 OCCs having led to an implanted embryo and the other including 58 OCCs having led to a non-implanted embryo. The average mtDNA content of CGCs was assessed by using a quantitative real-time PCR technique. RESULTS: Significantly higher mtDNA copy numbers in CGCs were associated with implanted embryos than with non-implanted embryos (mean 215 [sd 375] and 59 [sd 72], respectively; p < 10). Multivariate analysis, taking into account the women\u27s age, the embryo quality, and the AMH level, suggests an independent relationship between the mtDNA content of CGCs and the potential of embryo implantation. CONCLUSION: During in vitro fertilization (IVF) procedures, the probability of the implantation of the embryo appears to be closely correlated to the mtDNA copy numbers in the CGCs. Our results highlight the interest of mtDNA quantification in GCGs as a biomarker of the potential of embryo implantation

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Dégradation des MESFETs GaAs : mécanismes liés à l'interface GaAs/SiO2

Nous montrons que les dérives à long terme observées sur des MESFETs GaAs de puissance, protégés avec une couche de SiO2, sont dues à une dégradation de l'interface GaAs/SiO2. La mise en oeuvre de microanalyses Auger (taille du faisceau ≃ 0,1-0,2 μm), nous a permis d'identifier une exodiffusion de gallium, induite lors du dépôt de silice, ainsi qu'un mécanisme d'oxydation de GaAs pendant le fonctionnement. Ces réactions modifient les propriétés électriques de la surface dans les zones d'accès, expliquant ainsi les dérives observées sur les paramètres statiques et hyperfréquences

Dégradation des MESFETs GaAs : mécanismes liés à l'interface GaAs/SiO2

Long term degradation of GaAs power MESFET's protected with a SiO2 layer is shown to be surface-induced. Using micro-Auger analysis (beam spot size ≃ 0.1-0.2 μm), we have identified a gallium outdiffusion induced by the SiO2 surface protection deposition and a GaAs oxidation mechanism during electrical operation. These reactions modify the electrical surface properties in the access regions thus explaining the static and microwave performance degradations.Nous montrons que les dérives à long terme observées sur des MESFETs GaAs de puissance, protégés avec une couche de SiO2, sont dues à une dégradation de l'interface GaAs/SiO2. La mise en oeuvre de microanalyses Auger (taille du faisceau ≃ 0,1-0,2 μm), nous a permis d'identifier une exodiffusion de gallium, induite lors du dépôt de silice, ainsi qu'un mécanisme d'oxydation de GaAs pendant le fonctionnement. Ces réactions modifient les propriétés électriques de la surface dans les zones d'accès, expliquant ainsi les dérives observées sur les paramètres statiques et hyperfréquences