http://precedings.nature.com/tags/metabolism Recently posted documents tagged with 'metabolism' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/3224/version/1 Aside from leptin, galectin-12 is the only other gene exclusively expressed in mouse adipose tissue, suggesting an important role in energy homeostasis. The breakdown of triglycerides, or lipolysis, is a tightly controlled process to tailor fat mobilization according to the body’s energy status. Lipolysis is stimulated by hormones that signal energy demand, and suppressed the satiety hormone insulin. However, much still remains to be learned about the intracellular control of lipolytic signaling in adipocytes. Here we show that galectin-12 functions as an intrinsic negative regulator of lipolysis by modulating cyclic adenosine monophosphate (cAMP) levels. Galectin-12 deficiency reduced adiposity of mice on regular chow, alleviated obesity in old ob/ob mice, and accelerated fasting-induced fat mobilization in mice that had been fed a high-fat diet. This study identifies a critical intracellular function for galectin-12 in lipid metabolism that could have important implications for future research of galectins and human metabolic disorders. http://precedings.nature.com/documents/3224/version/1 Wed, 06 May 2009 16:15:41 UTC Ablation of Galectin-12 Results in Enhanced Lipolysis and Reduced Adiposity in Mice hdl:10101/npre.2009.3224.1 2009-05-06 Ri-Yao Yang Nature Precedings 2009-05-06T16:15:41Z Manuscript Molecular Cell Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1856/version/2 1. After weaning, human hunter-gatherer juveniles receive substantial (≈3.5-7 MJ day-1), extended (≈15 years) and reliable (kin and nonkin food pooling) energy provision.2. The childhood (pediatric) and the adult human brain takes a very high share of both basal metabolic rate (BMR) (child: 50-70%; adult: ≈20%) and total energy expenditure (TEE) (child: 30-50%; adult: ≈10%).3. The pediatric brain for an extended period (≈4-9 years-of-age) consumes roughly 50% more energy than the adult one, and after this, continues during adolescence, at a high but declining rate. Within the brain, childhood cerebral gray matter has an even higher 1.9 to 2.2-fold increased energy consumption. 4. This metabolic expensiveness is due to (i) the high cost of synapse activation (74% of brain energy expenditure in humans), combined with (ii), a prolonged period of exuberance in synapse numbers (up to double the number present in adults). Cognitive development during this period associates with volumetric changes in gray matter (expansion and contraction due to metabolic related size alterations in glial cells and capillary vascularization), and in white matter (expansion due to myelination). 5. Amongst mammals, anatomically modern humans show an unique pattern in which very slow musculoskeletal body growth is followed by a marked adolescent size/stature spurt. This pattern of growth contrasts with nonhuman primates that have a sustained fast juvenile growth with only a minor period of puberty acceleration. The existence of slow childhood growth in humans has been shown to date back to 160,000 BP. 6. Human children physiologically have a limited capacity to protect the brain from plasma glucose fluctuations and other metabolic disruptions. These can arise in adults, during prolonged strenuous exercise when skeletal muscle depletes plasma glucose, and produces other metabolic disruptions upon the brain (hypoxia, hyperthermia, dehydration and hyperammonemia). These are proportional to muscle mass.7. Children show specific adaptations to minimize such metabolic disturbances. (i) Due to slow body growth and resulting small body size, they have limited skeletal muscle mass. (ii) They show other adaptations such as an exercise specific preference for free fatty acid metabolism. (iii) While children are generally more active than adolescents and adults, they avoid physically prolonged intense exertion. 8. Childhood has a close relationship to high levels of energy provision and metabolic adaptations that support prolonged synaptic neurodevelopment. http://precedings.nature.com/documents/1856/version/2 Fri, 31 Oct 2008 13:34:12 UTC Human metabolic adaptations and prolonged expensive neurodevelopment: A review hdl:10101/npre.2008.1856.2 2008-10-31 John R. Skoyles Nature Precedings 2008-10-31T13:34:12Z Manuscript Developmental Biology Neuroscience Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1724/version/2 Taken together the Islets of Langerhans form a nutrient sensing network spread throughout the pancreas. They are tightly connected to the source organ – the intestine – and the target organs – liver, muscle, and fat cells. The expression of a unique set of proteins enables β cells, the most frequent islet cell type, to detect elevated blood glucose levels and secrete insulin accordingly. Neighbouring β-cells achieve tighter regulation of glucose-induced insulin secretion by coordination through cell surface proteins. They also adjust their secretory pathway capacity and flow to avoid being damaged. The immediate reaction of the β cell to nutrients is regulated by translational mechanisms, while longer term adaptations involve changes in transcription. Glucose increases protein synthesis in the β cell overall and especially that of some secretory proteins including insulin. This effect may be mediated through recognition of RNA motifs in the untranslated regions of those messengers. Failure of essential molecular components of the nutrient sensing system due to mutation or weakness paired with cellular stress can lead to dysfunctions, which on a larger scale manifest as diseases like diabetes mellitus. http://precedings.nature.com/documents/1724/version/2 Mon, 09 Jun 2008 14:32:18 UTC Pancreas islets in metabolic signaling – focus on the β-cell hdl:10101/npre.2008.1724.2 2008-07-01 Jakob Suckale Nature Precedings 2008-06-09T14:32:18Z Manuscript Molecular Cell Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1856/version/1 1. After weaning, human hunter-gatherer juveniles receive substantial (≈3.5-7 MJ day-1), extended (≈15 years) and reliable (kin and nonkin food pooling) energy provision.2. The childhood (pediatric) and the adult human brain takes a very high share of both basal metabolic rate (BMR) (child: 50-70%; adult: ≈20%) and total energy expenditure (TEE) (child: 30-50%; adult: ≈10%).3. The pediatric brain for an extended period (≈4-9 years-of-age) consumes roughly 50% more energy than the adult one, and after this, continues during adolescence, at a high but declining rate. Within the brain, childhood cerebral gray matter has an even higher 1.9 to 2.2-fold increased energy consumption. 4. This metabolic expensiveness is due to (i) the high cost of synapse activation (74% of brain energy expenditure in humans), combined with (ii), a prolonged period of exuberance in synapse numbers (up to double the number present in adults). Cognitive development during this period associates with volumetric changes in gray matter (expansion and contraction due to metabolic related size alterations in glial cells and capillary vascularization), and in white matter (expansion due to myelination). 5. Amongst mammals, anatomically modern humans show an unique pattern in which very slow musculoskeletal body growth is followed by a marked adolescent size/stature spurt. This pattern of growth contrasts with nonhuman primates that have a sustained fast juvenile growth with only a minor period of puberty acceleration. The existence of slow childhood growth in humans has been shown to date back to 160,000 BP. 6. Human children physiologically have a limited capacity to protect the brain from plasma glucose fluctuations and other metabolic disruptions. These can arise in adults, during prolonged strenuous exercise when skeletal muscle depletes plasma glucose, and produces other metabolic disruptions upon the brain (hypoxia, hyperthermia, dehydration and hyperammonemia). These are proportional to muscle mass.7. Children show specific adaptations to minimize such metabolic disturbances. (i) Due to slow body growth and resulting small body size, they have limited skeletal muscle mass. (ii) They show other adaptations such as an exercise specific preference for free fatty acid metabolism. (iii) While children are generally more active than adolescents and adults, they avoid physically prolonged intense exertion. 8. Childhood has a close relationship to high levels of energy provision and metabolic adaptations that support prolonged synaptic neurodevelopment. http://precedings.nature.com/documents/1856/version/1 Mon, 05 May 2008 19:15:24 UTC Human metabolic adaptations and prolonged expensive neurodevelopment: A review hdl:10101/npre.2008.1856.1 2008-05-05 John R. Skoyles Nature Precedings 2008-05-05T19:15:24Z Manuscript Developmental Biology Ecology Neuroscience http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1724/version/1 Taken together the Islets of Langerhans form a nutrient sensing network spread throughout the pancreas. They are tightly connected to the source organ – the intestine – and the target organs – liver, muscle, and fat cells. The expression of a unique set of proteins enables β cells, the most frequent islet cell type, to detect elevated blood glucose levels and secrete insulin accordingly. Neighbouring β-cells achieve tighter regulation of glucose-induced insulin secretion by coordination through cell surface proteins. They also adjust their secretory pathway capacity and flow to avoid being damaged. The immediate reaction of the β cell to nutrients is regulated by translational mechanisms, while longer term adaptations involve changes in transcription. Glucose increases protein synthesis in the β cell overall and especially that of some secretory proteins including insulin. This effect may be mediated through recognition of RNA motifs in the untranslated regions of those messengers. Failure of essential molecular components of the nutrient sensing system due to mutation or weakness paired with cellular stress can lead to dysfunctions, which on a larger scale manifest as diseases like diabetes mellitus. http://precedings.nature.com/documents/1724/version/1 Thu, 27 Mar 2008 19:04:52 UTC Pancreas islets in metabolic signaling – focus on the β-cell hdl:10101/npre.2008.1724.1 2008-03-27 Jakob Suckale Nature Precedings 2008-03-27T19:04:52Z Manuscript Molecular Cell Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1246/version/1 Background. Previous epidemiological and experimental studies indicated cholesterol as a central player in Alzheimer disease (AD). Here, we utilized skin fibroblasts and PBMC as possible ex vivo models for the study of dysfunctions of cholesterol homeostasis which may be related to AD development. Methods. We analyzed cholesterol homeostasis using colorimetric, thin layer chromatography (TLC), and histologic technique in ex vivo cultures of skin fibroblasts and PBMCs from patients with probable AD and their first-degree relatives. Additionally, healthy age-matched individuals served as controls. Findings. As compared to controls, skin fibroblasts and PBMCs from AD patients, displayed an evident alteration of cholesterol metabolism; namely an anomalous accumulation of cholesterol esters in their cytoplasm. No change in intracellular free cholesterol was observed. Cellular overloading of cholesterol esters was dramatically increased after specific growth stimulation of the different cell types. Cholesterol ester accumulation was negatively correlated to plasma levels of high density lipoprotein cholesterol (HDL-C) and positively correlated with severity of cognitive symptoms measured by Mini-Mental State Examination (MMSE). Inhibitors of cholesterol esterification, such as progesterone and SaH, as well as a potent inhibitor of cell proliferation, RAD, were able to prevent accumulation of cholesterol esters. Interpretation. Changes of cholesterol esters in the peripheral compartment may be indicative of a systemic alteration of intracellular cholesterol homeostasis, which in turn might create a cellular milieu favourable to the production of ß-amyloid in the brain. Pathways that control cholesterol esterification might represent promising targets for novel diagnostic and therapeutic AD approaches. http://precedings.nature.com/documents/1246/version/1 Thu, 08 Nov 2007 10:41:33 UTC Changes in Cholesterol Metabolism in Peripheral Cells of Alzheimer Disease Patients and Their Relatives hdl:10101/npre.2007.1246.1 2007-11-08 Alessandra Pani Nature Precedings 2007-11-08T10:41:33Z Manuscript Molecular Cell Biology Neuroscience http://creativecommons.org/licenses/by/2.5/ http://precedings.nature.com/documents/858/version/1 BackgroundIt has been previously reported that most mammalian genes display a circadian oscillation in their baseline expression. Consequently, the phase and amplitude of each component of a signal transduction cascade has downstream consequences. ResultsWe report our analysis of alternative transcripts in the leptin signaling pathway which is responsible for the systemic regulation of macronutrient storage and energy balance. We focused on the circadian expression pattern of a critical component of the leptin signaling system, suppressor of cytokine signaling 3 (SOCS3). On an Affymetrix GeneChip 430A2 microarray, this gene is represented by three probe sets targeting different regions within the 3’ end of the last exon. We demonstrate that in murine brown adipose tissue two downstream 3’ probe sets experience circadian baseline oscillation in counter-phase to the upstream probe set. Such differences in expression patterns are a telltale sign of alternative splicing within the last exon of SOCS3. In contrast, all three probe sets oscillated in a common phase in murine liver and white adipose tissue. This suggests that the regulation of SOCS3 expression in brown fat is tissue specific. Another component of the signaling pathway, Janus kinase (JAK), is directly regulated by SOCS and has alternative transcript probe sets oscillating in counter-phase in a white adipose tissue specific manner.ConclusionWe hypothesize that differential oscillation of alternative transcripts may provide a mechanism to maintain steady levels of expression in spite of circadian baseline variation. http://precedings.nature.com/documents/858/version/1 Thu, 30 Aug 2007 14:51:51 UTC Analysis of circadian pattern reveals tissue-specific alternative transcription in leptin signaling pathway hdl:10101/npre.2007.858.1 2007-08-30 Andrey Ptitsyn Nature Precedings 2007-08-30T14:51:51Z Manuscript Molecular Cell Biology Pharmacology Bioinformatics http://creativecommons.org/licenses/by/2.5/