Central nervous system regulation of adipocyte metabolism

The white adipose tissue was initially largely known only as an energy storage tissue. It is now well recognized that white adipose tissue is a major endocrine and secretory organ, which releases a wide range of protein signals and factors termed adipokines. The regulation of adipocyte metabolism is an important factor for the understanding of obesity, and some mechanisms are still unknown. Many homeostatic processes, including appetite and food intake, are controlled by neuroendocrine circuits involving the central nervous system. There is substantial evidence demonstrating that the central nervous system also directly regulates adipocyte metabolism. In this review, we discuss the central actions of some peptides with an important role in energy balance regulation on adipocyte metabolism and the physiological relevance of these actions.     

Basal metabolic rate and autonomic nervous system dysfunction in men with spinal cord injury

Objectives: The purpose of this study was to determine the relationship between autonomic nervous system dysfunction and basal metabolic rate (BMR), and the effect of spasticity on basal metabolic rate. Research Method and Procedures: Twenty men (11 paraplegic and 9 tetraplegic) with American Spinal Injury Association (ASIA)‐A and ‐B grade chronic spinal cord injury (SCI) participated in this study. Total body fat mass and lean tissue mass were measured in all participants using DXA by standard methods. Patients were allocated into 2 groups to determine the effect of autonomic nervous system dysfunction on BMR: Group I (T6 and upper‐level injuries with history of autonomic dysreflexia) and Group II (T7 and lower‐level injuries without history of autonomic dysreflexia). Measurements of BMR were determined by indirect calorimetry under standardized conditions. Results: There were 13 patients in Group I and 7 patients in Group II and the difference between these two in terms of time since injury, BMI, age, weight, lean tissue mass, BMR, and BMR/kg were not significant. Conclusion: We concluded that autonomic nervous system dysfunction does not affect BMR, and it might be ignored in considering energy needs in spinal cord injury.     

PML tumour suppression and beyond: Therapeutic implications

Recognition of the tumour suppressive capacity of the Promyelocytic Leukemia protein (PML) has emerged beyond its identification through APL, to a broad spectrum of tumors. This ability has chiefly been linked to its role as a core component of dynamic structures termed PML Nuclear Bodies (PML-NBs). In response to a variety of stresses, key factors and their molecular modifiers are recruited to PML-NBs, where activating modifications are facilitated, leading to a cellular stress response. PML was also found to perform anti-tumourigenic functions through cytoplasmic activities. Surprisingly, important recent research defined growth promoting capabilities of PML, which significantly challenges the notion of a ‘classic’ tumour suppressor. Through metabolic reprogramming, PML can afford a selective advantage for tumor cells in certain settings. The multiple forms in which PML exists are the likely explanation of this functional diversity. This behavioral ambiguity however raises a significant challenge to the design of strategies to therapeutically target PML. In this review we discuss this change of paradigm in the PML field and its ramifications, particularly for tailoring cancer therapies.     

Central nervous system myelin proteins of the coelacanth Latimeria chalumnae: phylogenetic implications

Synopsis Myelin was isolated from the brain of a coelacanth. Its protein components were separated by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS-PAGE). A protein component of 25000 Dalton was predominant; it was not glycosylated but reacted moderately with anti-mammalian CNS myelin proteolipid protein (PLP) antibodies and weakly with anti-lungfish CNS myelin glycosylated proteolipid protein (gPLP) antibodies. A component equivalent to mammalian DM-20 was not detectable. Presumably due to autolysis myelin basic protein (MBP) was not discernible by protein staining but showed up as a single band of 17000 Dalton with anti-mammalian MBP antibodies. Wolfgram protein (WP) was not present upon immunoblotting and the values for the myelin-specific 2, 3-cyclic nucleotide 3-phosphodiesterase (CNPase) were extremely low. These results question a chondrichthyan association of the coelacanth but are strongly in favor of an Actinistia-Tetrapoda sister group relationship, with Dipnoi being most closely related to that combined group.     

Variation in scorpion metabolic rate and rate-temperature relationships: implications for the fundamental equation of the metabolic theory of ecology

The fundamental equation of the metabolic theory of ecology (MTE) indicates that most of the variation in metabolic rate are a consequence of variation in organismal size and environmental temperature. Although evolution is thought to minimize energy costs of nutrient transport, its effects on metabolic rate via adaptation, acclimatization or acclimation are considered small, and restricted mostly to variation in the scaling constant, b(0). This contrasts strongly with many conclusions of evolutionary physiology and life-history theory, making closer examination of the fundamental equation an important task for evolutionary biologists. Here we do so using scorpions as model organisms. First, we investigate the implications for the fundamental equation of metabolic rate variation and its temperature dependence in the scorpion Uroplectes carinatus following laboratory acclimation. During 22 days of acclimation at 25 degrees C metabolic rates declined significantly (from 127.4 to 78.2 microW; P = 0.0001) whereas mean body mass remained constant (367.9-369.1 mg; P = 0.999). In field-fresh scorpions, metabolic rate-temperature (MRT) relationships varied substantially within and among individuals, and therefore had low repeatability values (tau = 0.02) and no significant among-individual variation (P = 0.181). However, acclimation resulted in a decline in within-individual variation of MRT slopes which subsequently revealed significant differences among individuals (P = 0.0031) and resulted in a fourfold increase in repeatability values (tau = 0.08). These results highlight the fact that MRT relationships can show substantial, directional variation within individuals over time. Using a randomization model we demonstrate that the reduction in metabolic rate with acclimation while body mass remains constant causes a decline both in the value of the mass-scaling exponent and the coefficient of determination. Furthermore, interspecific comparisons of activation energy, E, demonstrated significant variation in scorpions (0.09-1.14 eV), with a mean value of 0.77 eV, significantly higher than the 0.6-0.7 eV predicted by the fundamental equation. Our results add to a growing body of work questioning both the theoretical basis and empirical support for the MTE, and suggest that alternative models of metabolic rate variation incorporating explicit consideration of life history evolution deserve further scrutiny.     

Central nervous system antiretroviral efficacy in HIV infection: a qualitative and quantitative review and implications for future research

Background  

There is conflicting information as to whether antiretroviral drugs with better central nervous system (CNS) penetration (neuroHAART) assist in improving neurocognitive function and suppressing cerebrospinal fluid (CSF) HIV RNA. The current review aims to better synthesise existing literature by using an innovative two-phase review approach (qualitative and quantitative) to overcome methodological differences between studies.     

MicroRNAs and epigenetic regulation in the mammalian inner ear: implications for deafness

Sensorineural hearing loss is the most common sensory disorder in humans and derives, in most cases, from inner-ear defects or degeneration of the cochlear sensory neuroepithelial hair cells. Genetic factors make a significant contribution to hearing impairment. While mutations in 51 genes have been associated with hereditary sensorineural nonsyndromic hearing loss (NSHL) in humans, the responsible mutations in many other chromosomal loci linked with NSHL have not been identified yet. Recently, mutations in a noncoding microRNA (miRNA) gene, MIR96, which is expressed specifically in the inner-ear hair cells, were linked with progressive hearing loss in humans and mice. Furthermore, additional miRNAs were found to have essential roles in the development and survival of inner-ear hair cells. Epigenetic mechanisms, in particular, DNA methylation and histone modifications, have also been implicated in human deafness, suggesting that several layers of noncoding genes that have never been studied systematically in the inner-ear sensory epithelia are required for normal hearing. This review aims to summarize the current knowledge about the roles of miRNAs and epigenetic regulatory mechanisms in the development, survival, and function of the inner ear, specifically in the sensory epithelia, tectorial membrane, and innervation, and their contribution to hearing.     

Evaluation of the role of AMP-activated protein kinase and its downstream targets in mammalian hibernation

Mammalian hibernation requires an extensive reorganization of metabolism that typically includes a greater than 95% reduction in metabolic rate, selective inhibition of many ATP-consuming metabolic activities and a change in fuel use to a primary dependence on the oxidation of lipid reserves. We investigated whether the AMP-activated protein kinase (AMPK) could play a regulatory role in this reorganization. AMPK activity and the phosphorylation state of multiple downstream targets were assessed in five organs of thirteen-lined ground squirrels (Spermophilus tridecemlineatus) comparing euthermic animals with squirrels in deep torpor. AMPK activity was increased 3-fold in white adipose tissue from hibernating ground squirrels compared with euthermic controls, but activation was not seen in liver, skeletal muscle, brown adipose tissue or brain. Immunoblotting with phospho-specific antibodies revealed an increase in phosphorylation of eukaryotic elongation factor-2 at the inactivating Thr56 site in white adipose tissue, liver and brain of hibernators, but not in other tissues. Acetyl-CoA carboxylase phosphorylation at the inactivating Ser79 site was markedly increased in brown adipose tissue from hibernators, but no change was seen in white adipose tissue. No change was seen in the level of phosphorylation of the Ser565 AMPK site of hormone-sensitive lipase in adipose tissues of hibernating animals. In conclusion, AMPK does not appear to participate in the metabolic re-organization and/or the metabolic rate depression that occurs during ground squirrel hibernation.     

乳酸菌生理功能的系统解析与代谢调控

作为工业化的细胞工厂,乳酸菌广泛应用于食品、农业和医药等行业。然而在乳酸菌的工业生产中以及作为益生菌在人体胃肠道系统中都会面临多种环境胁迫,这些胁迫环境严重影响乳酸菌的生理功能,从而影响食品微生物制造的效率。近年来,随着代谢工程和系统生物学的发展,为乳酸菌生理功能的改造带来了前所未有的机遇。本文综述了系统生物学和代谢工程在乳酸菌生理功能的优化和调控中的具体应用。     

NRSF与神经系统发育调控

神经系统发育全程中,基因表达模式处于不断变化。这一动态过程是受到机体的精密调控的,NRSF是参与调控的重要分子之一。NRSF是一种含有锌指结构的转录因子,它与神经限制性沉默元件（NRSE／RE-11结合后能募集一些协同作用蛋白,通过组蛋白去乙酰化等机制抑制NRSE下游基因的转录。很多神经特异性基因和一些神经发育调节相关分子的基因序列中载有NRSE,NRSF正是通过动态调控这些基因的表达来调节神经系统发育。由于NRSF靶基因表达模式的变化是神经系统发育进程的重要分子基础,近年来对NRSF与神经系统发育调控的研究备受关注,通过阻断NRSF的异常作用来治疗神经退行性疾病己成为新的研究热点。     

Central metabolic fluxes in the endosperm of developing maize seeds and their implications for metabolic engineering

1?C labeling experiments performed with kernel cultures showed that developing maize endosperm is more efficient than other non-photosynthetic tissues such as sunflower and maize embryos at converting maternally supplied substrates into biomass. To characterize the metabolic fluxes in endosperm, maize kernels were labeled to isotopic steady state using 13C-labeled glucose. The resultant labeling in free metabolites and biomass was analyzed by NMR and GC-MS. After taking into account the labeling of substrates supplied by the metabolically active cob, the fluxes through central metabolism were quantified by computer-aided modeling. The flux map indicates that 51-69% of the ATP produced is used for biomass synthesis and up to 47% is expended in substrate cycling. These findings point to potential engineering targets for improving yield and increasing oil contents by, respectively, reducing substrate cycling and increasing the commitment of plastidic carbon into fatty acid synthesis at the level of pyruvate kinase.     

瘦蛋白对摄食和能量平衡的调节及其在哺乳动物冬眠中的作用

白色脂肪合成和分泌的瘦蛋白(leptin)作用于下丘脑和外周的代谢产热器官,对摄食和能量平衡起调节作用。摄食和能量平衡的失调,如瘦蛋白抵抗,可以导致肥胖等一系列生理疾病。以体内贮存的脂肪为主要能源物质越冬的冬眠哺乳动物,体重的年周期波动幅度巨大,其摄食和能量平衡调节机制可能不同于一般的非冬眠物种,育肥阶段可能存在瘦蛋白抵抗机制。本文总结了瘦蛋白调节摄食和能量平衡的作用机制以及瘦蛋白对冬眠哺乳动物育肥和冬眠的影响,为进一步研究冬眠哺乳动物的能量平衡提供参考。