Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding.

Weight regain after caloric restriction results in accelerated fat storage in adipose tissue. This catch-up fat phenomenon is postulated to result partly from suppressed skeletal muscle thermogenesis, but the underlying mechanisms are elusive. We investigated whether the reduced rate of skeletal muscle contraction-relaxation cycle that occurs after caloric restriction persists during weight recovery and could contribute to catch-up fat. Using a rat model of semistarvation-refeeding, in which fat recovery is driven by suppressed thermogenesis, we show that contraction and relaxation of leg muscles are slower after both semistarvation and refeeding. These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers. These semistarvation-induced changes persisted during recovery and correlated with impaired expression of transcription factors involved in slow-twitch muscle development. We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility. These energy-sparing effects persist during weight recovery and contribute to catch-up fat.

A macro-ecological perspective on crassulacean acid metabolism (CAM) photosynthesis evolution in Afro-Madagascan drylands: Eulophiinae orchids as a case study.

Crassulacean acid metabolism (CAM) photosynthesis is an adaptation to water and atmospheric CO2 deficits that has been linked to diversification in dry-adapted plants. We investigated whether CAM evolution can be associated with the availability of new or alternative niches, using Eulophiinae orchids as a case study. Carbon isotope ratios, geographical and climate data, fossil records and DNA sequences were used to: assess the prevalence of CAM in Eulophiinae orchids; characterize the ecological niche of extant taxa; infer divergence times; and estimate whether CAM is associated with niche shifts. CAM evolved in four terrestrial lineages during the late Miocene/Pliocene, which have uneven diversification patterns. These lineages originated in humid habitats and colonized dry/seasonally dry environments in Africa and Madagascar. Additional key features (variegation, heterophylly) evolved in the most species-rich CAM lineages. Dry habitats were also colonized by a lineage that includes putative mycoheterotrophic taxa. These findings indicate that the switch to CAM is associated with environmental change. With its suite of adaptive traits, this group of orchids represents a unique opportunity to study the adaptations to dry environments, especially in the face of projected global aridification.

Retinoblastoma Protein Knockdown Favors Oxidative Metabolism and Glucose and Fatty Acid Disposal in Muscle Cells.

Deficiency in the retinoblastoma protein (Rb) favors leanness and a healthy metabolic profile in mice largely attributed to activation of oxidative metabolism in white and brown adipose tissues. Less is known about Rb modulation of skeletal muscle metabolism. This was studied here by transiently knocking down Rb expression in differentiated C2C12 myotubes using small interfering RNAs. Compared with control cells transfected with non-targeting RNAs, myotubes silenced for Rb (by 80-90%) had increased expression of genes related to fatty acid uptake and oxidation such as Cd36 and Cpt1b (by 61% and 42%, respectively), increased Mitofusin 2 protein content (∼2.5-fold increase), increased mitochondrial to nuclear DNA ratio (by 48%), increased oxygen consumption (by 65%) and decreased intracellular lipid accumulation. Rb silenced myotubes also displayed up-regulated levels of glucose transporter type 4 expression (∼5-fold increase), increased basal glucose uptake, and enhanced insulin-induced Akt phosphorylation. Interestingly, exercise in mice led to increased Rb phosphorylation (inactivation) in skeletal muscle as evidenced by immunohistochemistry analysis. In conclusion, the silencing of Rb enhances mitochondrial oxidative metabolism and fatty acid and glucose disposal in skeletal myotubes, and changes in Rb status may contribute to muscle physiological adaptation to exercise. J. Cell. Physiol. 231: 708-718, 2016. © 2015 Wiley Periodicals, Inc.

Erreurs innées du métabolisme: transition enfant-adulte [Inborn errors of metabolism: transition from childhood to adulthood].

Les erreurs innées du métabolisme (EIM) sont dues à des mutations de gènes codant pour des enzymes du métabolisme et sont classées selon trois grands groupes de maladies: 1) intoxications; 2) déficit énergétique et 3) déficit de synthèse ou catabolisme des maladies complexes. Le progrès thérapeutique des vingt dernières années a permis d'améliorer le pronostic des enfants atteints d'EIM. Ces enfants grandissent et doivent être pris en charge à l'adolescence et à l'âge adulte par des équipes spécialisées. Cette médecine métabolique pour adultes est une discipline relativement nouvelle avec une information limitée chez l'adulte. Les recommandations pédiatriques sont extrapolées à la prise en charge des adultes tout en intégrant les différentes étapes de vie (indépendance sociale, grossesse, vieillissement et éventuelles complications tardives). Inborn errors of metabolism (IEM) are due to mutations of genes coding for enzymes of intermediary metabolism and are classified into 3 broad categories: 1) intoxication, 2) energy defect and 3) cellular organelles synthesis or catabolism defect. Improvements of therapy over these last 20 years has improved prognosis of children with IEM. These children grow up and should have their transition to specialized adult care. Adult patients with IEM are a relatively new phenomenon with currently only limited knowledge. Extrapolated pediatric guidelines are applied to the adult population taking into account adult life stages (social independence, pregnancy, aging process and potential long-term complications).

Iron metabolism and incidence of metabolic syndrome.

BACKGROUND AND AIMS: Whether iron metabolism affects metabolic syndrome (METS) is debated. We assessed the association between several markers of iron metabolism and incidence of METS. METHODS AND RESULTS: Data from 3271 participants (1870 women, 51.3 ± 10.4 years), free of METS at baseline and followed for 5.5 years. The association of serum iron, ferritin and transferrin with incident METS was assessed separately by gender. Incidence of METS was 22.6% in men and 16.5% in women (p < 0.001). After multivariate adjustment, a positive association was found between transferrin and incident METS in men: odds ratio (OR) and 95% confidence interval for the fourth relative to the first quartile 1.55 (1.04-2.31), p for trend = 0.03, while no association was found for iron OR = 0.81 (0.53-1.24), p for trend = 0.33 and ferritin OR = 1.30 (0.88-1.92), p for trend = 0.018. In women, a negative association was found between iron and incident METS: OR for the fourth relative to the first quartile 0.51 (0.33-0.80), p for trend<0.03; the association between transferrin and incident METS was borderline significant: OR = 1.45 (0.97-2.17), p for trend = 0.07 and no association was found for ferritin: OR = 1.11 (0.76-1.63), p for trend = 0.58. CONCLUSION: Transferrin, not ferritin, is independently associated with an increased risk of incident METS; the protective effect of iron in women should be further explored.

Markers of iron metabolism and metabolic syndrome in Swiss adults

Plusieurs études populationnelles ont montré l'existence d'une association entre des taux sanguins élevés de transferrine et le syndrome métabolique (SM). Bien que cette association soit bien établie, restent encore à être décrites les associations entre le SM et les autres marqueurs sanguins du métabolisme du fer, tels que le fer, la transferrine (Tsf), la capacité totale de fixation de la transferrine (CTF) ou la saturation de la transferrine (SaTsf) sanguins. Le but de notre étude a été d'identifier les associations entre les différents marqueurs du métabolisme du fer (fer, ferritine, Tsf, CTF et SaTsf) et le SM. Les données de l'étude CoLaus, récoltées entre 2003 et 2006, ont été utilisées. Le SM était défini selon les critères du National Cholesterol Education Program Adult Panel III. L'analyse statistique a été faite en stratifiant selon le genre ainsi que le status ménopausal chez les femmes. Des 6733 participants, 1235 (18%) ont été exclus de fait d'absence de données concernant les variables qui nous intéressaient, ou chez qui nous avons soupçonné une possible hémochromatose non diagnostiquée (SaTsf> 50%). Des 5498 participants restant (âge moyen ± écart-type: 53 ± 11 ans), 2596 étaient des hommes, 1285 des femmes pré- et 1617 des femmes postménopausées. La prévalence du SM était de 29,4% chez les hommes, 8,3% et 25,5% chez les femmes pré- et postménopausées, respectivement. Dans les trois groupes, la prévalence du SM était la plus haute dans les quartiles les plus élevés de ferritine, Tsf et CTF, ainsi que dans le quartile le plus bas de SaTsf. Après ajustement sur l'âge, l'indice de masse corporelle, la protéine C réactive, la consommation de tabac et/ou d'alcool, la prise de suppléments en fer et les marqueurs hépatiques, l'appartenance au quartile le plus élevé de ferritine, Tsf ou CTF était associée à un risque plus important de SM chez les hommes et les femmes postménopausées : Odds ratio (OR) et [intervalle de confiance à 95%] pour la ferritine 1.44 [1.07-1.94] et 1.47 [0.99-2.17]; pour la Tsf et la CTF, OR=1.43 [1.06-1.91] et 2.13 [1.44-3.15] pour les hommes et les femmes postménopausées, respectivement. Au contraire, l'appartenance au quartile le plus élevé de la SaTsf était associé à un risque moins important de SM: OR=0.77 [0.57-1.05] et 0.59 [0.39-0.90] pour les hommes et les femmes postménopausées, respectivement. Il n'y avait aucune association entre les marqueurs sanguins du métabolisme du fer et le SM chez les femmes préménopausées, ni entre le fer sanguin et le SM chez les trois groupes. En conclusion, la majorité des marqueurs sanguins du métabolisme du fer, mais pas le fer lui-même, sont associés de manière indépendante au SM chez les hommes et les femmes postménopausées. -- Context: Excessive iron storage has been associated with metabolic syndrome (MS). Objective: To assess the association between markers of iron metabolism and MS in a healthy population. Design: Cross-sectional study conducted between 2003 and 2006. Setting: Population-based study in Lausanne, Switzerland. Patients: 5,498 participants aged 35-75 years, stratified by sex and menopausal status. Participants with transferrin saturation (TSAT) >50% were excluded. Intervention: None. Main Outcome Measures: serum iron, ferritin, transferrin, total iron binding capacity (TIBC) and TSAT. MS was defined according to ATP-III criteria. Results: Prevalence of MS was 29.4% in men, 8.3% in premenopausal and 25.5% in postmenopausal women. On bivariate analysis, the highest prevalence of MS occurred in the highest quartiles of serum ferritin, transferrin and TIBC, and in the lowest quartile of TSAT. After multivariate adjustment for age, body mass index, C-reactive protein, smoking, alcohol, liver markers and iron supplementation, men and postmenopausal women in the highest quartile of serum ferritin, transferrin and TIBC had a higher risk of presenting with MS: for ferritin, Odds ratio and [95% CI]=1.44 [1.07-1.94] for men and 1.47 [0.99-2.17] for postmenopausal women; for transferrin and TIBC, OR=1.43 [1.06-1.91] and 2.13 [1.44-3.15], Participants in the highest quartile of TSAT had a lower risk of MS: OR=0.77 [0.57-1.05] for men and 0.59 [0.39-0.90] for postmenopausal women. No association was found between iron and MS and between markers of iron metabolism and MS in premenopausal women. Conclusion: Ferritin, transferrin, TIBC are positively and TSAT is negatively associated with MS in men and postmenopausal women.

Cerebral Lactate Metabolism After Traumatic Brain Injury.

Cerebral energy dysfunction has emerged as an important determinant of prognosis following traumatic brain injury (TBI). A number of studies using cerebral microdialysis, positron emission tomography, and jugular bulb oximetry to explore cerebral metabolism in patients with TBI have demonstrated a critical decrease in the availability of the main energy substrate of brain cells (i.e., glucose). Energy dysfunction induces adaptations of cerebral metabolism that include the utilization of alternative energy resources that the brain constitutively has, such as lactate. Two decades of experimental and human investigations have convincingly shown that lactate stands as a major actor of cerebral metabolism. Glutamate-induced activation of glycolysis stimulates lactate production from glucose in astrocytes, with subsequent lactate transfer to neurons (astrocyte-neuron lactate shuttle). Lactate is not only used as an extra energy substrate but also acts as a signaling molecule and regulator of systemic and brain glucose use in the cerebral circulation. In animal models of brain injury (e.g., TBI, stroke), supplementation with exogenous lactate exerts significant neuroprotection. Here, we summarize the main clinical studies showing the pivotal role of lactate and cerebral lactate metabolism after TBI. We also review pilot interventional studies that examined exogenous lactate supplementation in patients with TBI and found hypertonic lactate infusions had several beneficial properties on the injured brain, including decrease of brain edema, improvement of neuroenergetics via a "cerebral glucose-sparing effect," and increase of cerebral blood flow. Hypertonic lactate represents a promising area of therapeutic investigation; however, larger studies are needed to further examine mechanisms of action and impact on outcome.

Enzymes of yeast polyphosphate metabolism: structure, enzymology and biological roles.

Inorganic polyphosphate (polyP) is found in all living organisms. The known polyP functions in eukaryotes range from osmoregulation and virulence in parasitic protozoa to modulating blood coagulation, inflammation, bone mineralization and cellular signalling in mammals. However mechanisms of regulation and even the identity of involved proteins in many cases remain obscure. Most of the insights obtained so far stem from studies in the yeast Saccharomyces cerevisiae. Here, we provide a short overview of the properties and functions of known yeast polyP metabolism enzymes and discuss future directions for polyP research.