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861.
Xiaoyan Hui Weidong Zhu Yu Wang Karen S. L. Lam Jialiang Zhang Donghai Wu Edward W. Kraegen Yixue Li Aimin Xu 《The Journal of biological chemistry》2009,284(21):14050-14057
Major urinary protein-1 (MUP-1) is a low molecular weight secreted protein
produced predominantly from the liver. Structurally it belongs to the
lipocalin family, which carries small hydrophobic ligands such as pheromones.
However, the physiological functions of MUP-1 remain poorly understood. Here
we provide evidence demonstrating that MUP-1 is an important player in
regulating energy expenditure and metabolism in mice. Both microarray and
real-time PCR analysis demonstrated that the MUP-1 mRNA abundance in the liver
of db/db obese mice was reduced by ∼30-fold compared
with their lean littermates, whereas this change was partially reversed by
treatment with the insulin-sensitizing drug rosiglitazone. In both dietary and
genetic obese mice, the circulating concentrations of MUP-1 were markedly
decreased compared with the lean controls. Chronic elevation of circulating
MUP-1 in db/db mice, using an osmotic pump-based protein
delivery system, increased energy expenditure and locomotor activity, raised
core body temperature, and decreased glucose intolerance as well as insulin
resistance. At the molecular level, MUP-1-mediated improvement in metabolic
profiles was accompanied by increased expression of genes involved in
mitochondrial biogenesis, elevated mitochondrial oxidative capacity, decreased
triglyceride accumulation, and enhanced insulin-evoked Akt signaling in
skeletal muscle but not in liver. Altogether, these findings raise the
possibility that MUP-1 deficiency might contribute to the metabolic
dysregulation in obese/diabetic mice, and suggest that the beneficial
metabolic effects of MUP-1 are attributed in part to its ability in increasing
mitochondrial function in skeletal muscle.The liver is the primary organ for carbohydrate and lipid metabolism,
including gluconeogenesis, glycogenesis, cholesterol biosynthesis, and
lipogenesis (1,
2). These metabolic events in
the liver are tightly controlled by several pancreatic hormones including
insulin and glucagon. In addition, the liver itself is one of the largest
endocrine organs in the body, secreting numerous humoral factors involved in
the regulation of systemic glucose and lipid homeostasis. The importance of
the liver-derived humoral factors in maintaining glucose metabolism is
highlighted by the observation that glucose uptake by skeletal muscle is
severely impaired by surgical or pharmacological blockade of hepatic
parasympathetic nerves (3). In
the past several years, a number of liver-derived humoral metabolic factors,
including bone morphogenetic protein-9 (BMP-9)
(4), fibroblast growth factor
21 (FGF21)
(5–7),
retinol-binding protein 4 (RBP4)
(8,
9), adropin
(10), and angiopoietin-like
proteins (Angptl) 3, 4, and 6
(11–13),
have been identified, and their roles in glucose and lipid metabolism have
been characterized in great detail. Noticeably, BMP-9, FGF21, and Angptl6
exhibit potent insulin-sensitizing and glucose-lowering effects in animal
models, and they have been proposed as potential candidates for the treatment
of insulin resistance and type II diabetes
(4,
6,
7,
13).To search for novel liver-derived secretory factors involved in the
regulation of glucose homeostasis, we used microarray analysis as a global
screening for systematic identification of genes differentially expressed in
the liver of C57BLKS db/db mice (a genetically inherited
diabetic mouse model that is characterized by severe insulin resistance and
hyperglycemia) and their lean littermates. We found that the mRNA level of
mouse major urinary protein-1
(MUP-1)2 was markedly
down-regulated in db/db mice, and the change was largely
normalized upon treatment with the PPARγ agonist rosiglitazone. MUP-1 is
a small molecular weight secreted protein abundantly expressed in the liver
(14). Its expression in the
liver is enhanced by administration of the hepatotoxic agent
dimethylnitrosamine (15) but
is reduced by interleukin 6-induced acute phase response in mice
(16). Like other members of
the MUP family, MUP-1 has been proposed to act as a pheromone-binding protein
in urine (17), thereby
accelerating puberty and promoting aggressive behavior in male mice. However,
the precise functions of MUPs have yet to be determined.MUP-1 belongs to the lipocalin superfamily, the members of which share a
common tertiary structure with a cup-shaped hydrophobic ligand binding pocket
surrounded by an eight-stranded β-barrel
(18,
19). This structure confers
upon lipocalins the ability to bind and transport a wide variety of small
lipophilic substances, including fatty acids, cholesterols, prostaglandins,
and pheromones. Noticeably, several members of the lipocalin family, including
RBP4, lipocalin-2, and adipocyte fatty acid-binding protein (A-FABP), have
recently been shown to be important mediators of obesity-related insulin
resistance and glucose intolerance
(8,
20–22).
Unlike MUP-1, the expression of RBP4, lipocalin-2, and A-FABP are elevated in
obesity and diabetes (9,
20,
23).In this study, we investigated the metabolic role of MUP-1 in mice. Our
results demonstrated that MUP-1 was abundantly present in the circulation. In
genetic and dietary obese mouse models, the serum and urine concentrations of
MUP-1 were remarkably decreased. Replenishment of recombinant MUP-1 led to
improved glucose tolerance and insulin sensitivity, as well as increased
energy expenditure and locomotor activity in db/db diabetic
mice. Our data suggest that MUP-1 not only serves as a circulating biomarker,
negatively correlated with obesity-related metabolic disorders, but also plays
an active role in regulating energy homeostasis and insulin sensitivity in
mice. 相似文献
862.
Using the ecosystem services approach for better planning and conservation of urban green spaces: a Finland case study 总被引:6,自引:0,他引:6
Jari Niemelä Sanna-Riikka Saarela Tarja Söderman Leena Kopperoinen Vesa Yli-Pelkonen Seija Väre D. Johan Kotze 《Biodiversity and Conservation》2010,19(11):3225-3243
Ecosystem services are vital for humans in urban regions. However, urban development poses a great risk for the ability of
ecosystems to provide these services. In this paper we first address the most important ecosystem services in functional urban
regions in Finland. Well accessible and good quality recreational ecosystem services, for example, provided by urban nature,
are an important part of a high-quality living environment and important for public health. Vegetation of urban regions can
have a role in carbon dioxide sequestration and thus in climate change mitigation. For instance, estimates of carbon sinks
can be compared to total CO2 emissions of an urban region, and the municipality can aim at both increasing carbon sinks and decreasing CO2 emissions with proper land-use planning. Large and contiguous core nature areas, smaller green areas and ecological connections
between them are the essence of regional ecological networks and are essential for maintaining interconnected habitats for
species and thus biological diversity. Thus, both local and regional level ecological networks are vital for maintaining ecosystem
services in urban regions. The impacts of climate change coupled with land-use and land cover change will bring serious challenges
for maintaining ecosystem services in urban areas. Although not yet widely used in planning practices, the ecosystem services
approach can provide an opportunity for land-use planning to develop ecologically sustainable urban regions. Currently, information
on ecosystem services of urban regions is lacking and there is a need to improve the knowledge base for land-use planning. 相似文献
863.
Stefan Vogt-Geisse 《Journal of molecular modeling》2016,22(5):110
With increasing computational capabilities, an ever growing amount of data is generated in computational chemistry that contains a vast amount of chemically relevant information. It is therefore imperative to create new computational tools in order to process and extract this data in a sensible way. Kudi is an open source library that aids in the extraction of chemical properties from reaction paths. The straightforward structure of Kudi makes it easy to use for users and allows for effortless implementation of new capabilities, and extension to any quantum chemistry package. A use case for Kudi is shown for the tautomerization reaction of formic acid. Kudi is available free of charge at www.github.com/stvogt/kudi 相似文献
864.
作者对新疆维吾尔自治区的9个市、县进行了药用延胡索的资源调查,采集植物标本70余份,弄清药用种类主要是3种,即Corydalis glaucescens Regel,C.ledebouriana Kir.et Kar.和C.schanginii(Pall.)Fedtsch.;初步了解了3种药用延胡索植物的分布状况,并对块茎中总生物碱的含量作了分析。 相似文献
865.
866.
Semantic integration to identify overlapping functional modules in protein interaction networks 总被引:4,自引:0,他引:4
Background
The systematic analysis of protein-protein interactions can enable a better understanding of cellular organization, processes and functions. Functional modules can be identified from the protein interaction networks derived from experimental data sets. However, these analyses are challenging because of the presence of unreliable interactions and the complex connectivity of the network. The integration of protein-protein interactions with the data from other sources can be leveraged for improving the effectiveness of functional module detection algorithms. 相似文献867.
Background
Paulinella chromatophora is a freshwater filose amoeba with photosynthetic endosymbionts (chromatophores) of cyanobacterial origin that are closely related to free-living Prochlorococcus and Synechococcus species (PS-clade). Members of the PS-clade of cyanobacteria contain a proteobacterial form 1A RubisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase) that was acquired by horizontal gene transfer (HGT) of a carboxysomal operon. In rDNA-phylogenies, the Paulinella chromatophore diverged basal to the PS-clade, raising the question whether the HGT occurred before or after the split of the chromatophore ancestor. 相似文献868.
Jack Lee David Nordsletten Andrew Cookson Simone Rivolo Nicolas Smith 《Biomechanics and modeling in mechanobiology》2016,15(6):1535-1555
Coronary wave intensity analysis (cWIA) is a diagnostic technique based on invasive measurement of coronary pressure and velocity waveforms. The theory of WIA allows the forward- and backward-propagating coronary waves to be separated and attributed to their origin and timing, thus serving as a sensitive and specific cardiac functional indicator. In recent years, an increasing number of clinical studies have begun to establish associations between changes in specific waves and various diseases of myocardium and perfusion. These studies are, however, currently confined to a trial-and-error approach and are subject to technological limitations which may confound accurate interpretations. In this work, we have developed a biophysically based cardiac perfusion model which incorporates full ventricular–aortic–coronary coupling. This was achieved by integrating our previous work on one-dimensional modelling of vascular flow and poroelastic perfusion within an active myocardial mechanics framework. Extensive parameterisation was performed, yielding a close agreement with physiological levels of global coronary and myocardial function as well as experimentally observed cumulative wave intensity magnitudes. Results indicate a strong dependence of the backward suction wave on QRS duration and vascular resistance, the forward pushing wave on the rate of myocyte tension development, and the late forward pushing wave on the aortic valve dynamics. These findings are not only consistent with experimental observations, but offer a greater specificity to the wave-originating mechanisms, thus demonstrating the value of the integrated model as a tool for clinical investigation. 相似文献
869.
不同光强下高锰对黄瓜光合作用特性的影响 总被引:10,自引:2,他引:10
采用营养液培养的方法,研究了不同光强下高锰对黄瓜植株生长、叶绿素含量、叶绿素荧光参数和光合作用的影响.结果表明,高锰处理抑制了黄瓜植株的生长,与弱光处理相比强光下抑制幅度更加显著.强光下,高锰处理显著降低叶绿素含量,但降低光强却增加其含量.强光下,高锰处理显著降低原初光能转换效率(Fv/Fm)、光合电子传递量子效率(ΦPSII)和光化学猝灭系数(qP);弱光下,高锰处理对Fv/Fm和qP无显著影响.高锰处理使净光合速率(Pn)和气孔导度(Gs)下降.尤其是在强光下下降幅度更大.高锰处理使细胞间CO2浓度(Ci)在强光下升高,而在弱光下则下降.与Ci相反,高锰处理使气孔限制值(Ls)在强光下下降,而在弱光下上升.因此,强光下高锰胁迫使净光合速率下降可能是由非气孔限制引起的,而弱光下高锰处理使净光合速率下降可能是由气孔因子限制引起的. 相似文献
870.