• liver
  • In humans, rosiglitazone reduces whole-body insulin resistance by its insulin-sensitizing effect on muscle, adipose tissue, and liver ( 16 - 18 ). (diabetesjournals.org)
  • Meaningful expression of the FGF21 coreceptor β-Klotho was restricted to liver and WAT in a survey of 15 tissues that included the mammary gland. (wikipedia.org)
  • Elevated levels also correlate with liver fat content in non-alcoholic fatty liver disease and positively correlate with BMI in humans suggesting obesity as a FGF21-resistant state. (wikipedia.org)
  • However, its main function is to be a reserve of lipids, which can be oxidised to meet the energy needs of the body and to protect it from excess glucose by storing triglycerides produced by the liver from sugars, although some evidence suggests that most lipid synthesis from carbohydrates occurs in the adipose tissue itself. (wikipedia.org)
  • Once within cells, glucose is rapidly phosphorylated by glucokinase in the liver and hexokinase in other tissues to form glucose-6-phosphate, which then enters glycolysis or is polymerized into glycogen. (wikipedia.org)
  • As the body takes in energy in the form of glucose, some is expended, and the rest is stored as glycogen primarily in the liver, muscle cells, or fat. (wikipedia.org)
  • Ketone bodies Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise, alcoholism or in untreated (or inadequately treated) type 1 diabetes mellitus. (wikipedia.org)
  • They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted (these glycogen stores are depleted after only 24 hours of fasting). (wikipedia.org)
  • Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. (wikipedia.org)
  • Acetone is the decarboxylated form of acetoacetate which cannot be converted back into acetyl-CoA except via detoxification in the liver where it is converted into lactic acid, which can, in turn, be oxidized into pyruvic acid, and only then into acetyl-CoA. (wikipedia.org)
  • This is the fate of acetyl-CoA wherever β-oxidation of fatty acids occurs, except under certain circumstances in the liver. (wikipedia.org)
  • Under these circumstances oxaloacetate is hydrogenated to malate which is then removed from the mitochondrion to be converted into glucose in the cytoplasm of the liver cells, from where it is released into the blood. (wikipedia.org)
  • The hormone plays a role in the suppression of the metabolic derangements that may result in type 2 diabetes, obesity, atherosclerosis, non-alcoholic fatty liver disease (NAFLD) and an independent risk factor for metabolic syndrome. (wikipedia.org)
  • The major sites of fatty acid synthesis are adipose tissue and the liver. (wikipedia.org)
  • Lipogenic gene expression in the liver via glucose and insulin is moderated by SREBP-1. (wikipedia.org)
  • gene
  • One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferator-activated receptor γ (PPAR γ ), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. (nature.com)
  • Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor that in humans is encoded by the PPARG gene. (wikipedia.org)
  • Group XVI phospholipase A2 also commonly known as adipocyte phospholipase A2 (AdPLA) is an enzyme that in humans is encoded by the PLA2G16 gene. (wikipedia.org)
  • The formation of adipose tissue appears to be controlled in part by the adipose gene. (wikipedia.org)
  • Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial is an enzyme that in humans is encoded by the PDK4 gene. (wikipedia.org)
  • Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. (wikipedia.org)
  • The mature protein encoded by the PDK4 gene contains 294 amino acids in its sequence. (wikipedia.org)
  • ANGPTL8 (also known as lipasin, originally Betatrophin) is a protein that in humans is encoded by the C19orf80 gene. (wikipedia.org)
  • The gene for betatrophin lies on mouse chromosome 9 (gene symbol: Gm6484) and on human chromosome 19 (gene symbol: C19orf80). (wikipedia.org)
  • Glucose transporter type 4 (GLUT-4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the SLC2A4 gene. (wikipedia.org)
  • In humans it is encoded by the ADIPOQ gene and it is produced in adipose tissue. (wikipedia.org)
  • The interaction of glucose and lipogenic gene expression is assumed to be managed by the increasing concentration of an unknown glucose metabolite through the activity of glucokinase. (wikipedia.org)
  • Adiponectin receptor 1 (AdipoR1) is a protein which in humans is encoded by the ADIPOR1 gene. (wikipedia.org)
  • Human ADIPOR1 genome location and ADIPOR1 gene details page in the UCSC Genome Browser. (wikipedia.org)
  • adipogenesis
  • Despite the identification of key regulators of beige adipogenesis, impacts of dietary factors on adaptive thermogenesis are largely unknown, partly due to a lack of validated human cell models. (springer.com)
  • Bone morphogenetic protein 7 (BMP7) is known to promote brown adipogenesis in rodent and human progenitor cells. (springer.com)
  • The genes activated by PPARG stimulate lipid uptake and adipogenesis by fat cells. (wikipedia.org)
  • Adipocyte hypotrophy was attributed primarily to reduced triacylglyceride content in WAT from lipolysis, while adipocyte differentiation did not play a role in reduced adipose tissue despite the effects of prostaglandins on adipogenesis. (wikipedia.org)
  • peripheral
  • Additionally, central resistin promotes the activation of the serine kinases Jun NH 2 -terminal kinase and p38 mitogen-activated protein kinase, enhances the serine phosphorylation of insulin receptor substrate-1, and increases the expression of the proinflammatory cytokine interleukin-6 in the hypothalamus and key peripheral insulin-sensitive tissues. (diabetesjournals.org)
  • Peripheral administration or transgenic overexpression of resistin impairs insulin action in insulin-sensitive tissues ( 14 - 16 ). (diabetesjournals.org)
  • Saturated fatty acids activate both hypothalamic and peripheral TLR4 signaling, leading to proinflammatory cytokine production and endoplasmic reticulum stress ( 30 - 32 ). (diabetesjournals.org)
  • VLDL particles are secreted directly into blood, where they mature and function to deliver the endogenously derived lipids to peripheral tissues. (wikipedia.org)
  • This has the effect of increasing the half-life of the hormone and decreasing the rate at which it is taken up by peripheral tissues. (wikipedia.org)
  • adiponectin
  • CONCLUSIONS Low plasma adiponectin levels are independently associated with increased risk of T2DM in patients with MI and added significantly to the predictive value of blood glucose. (diabetesjournals.org)
  • Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone which is involved in regulating glucose levels as well as fatty acid breakdown. (wikipedia.org)
  • Adiponectin is a 244-amino-acid-long polypeptide (protein). (wikipedia.org)
  • Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid oxidation. (wikipedia.org)
  • Adiponectin is secreted from adipose tissue (and also from the placenta in pregnancy) into the bloodstream and is very abundant in plasma relative to many hormones. (wikipedia.org)
  • Circulating adiponectin concentrations increase during caloric restriction in animals and humans, such as in patients with anorexia nervosa. (wikipedia.org)
  • This observation is surprising, given that adiponectin is produced by adipose tissue. (wikipedia.org)
  • However, a recent study suggests that adipose tissue within bone marrow, which increases during caloric restriction, contributes to elevated circulating adiponectin in this context. (wikipedia.org)
  • So far, two receptors have been identified with homology to G protein-coupled receptors, and one receptor similar to the cadherin family: Adiponectin receptor 1 (AdipoR1) Adiponectin receptor 2 (AdipoR2) T-cadherin - CDH13 These have distinct tissue specificities within the body and have different affinities to the various forms of adiponectin. (wikipedia.org)
  • hormones
  • Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as leptin, estrogen, resistin, and the cytokine TNFα. (wikipedia.org)
  • On the other hand, adipose tissue is known to secrete various metabolites, hormones and cytokines that may play a role in causing hyperinsulinemia. (wikipedia.org)
  • As a result of its slow digestion, isomaltulose occurs more distally in the human small intestine than does sucrose, as evidenced by their different incretion hormones responses. (wikipedia.org)
  • Other hormones that prevent the stimulation of lipogenesis in adipose cells are growth hormones (GH). (wikipedia.org)
  • One proposed mechanism for how the hormone works is that growth hormones affects insulin signaling thereby decreasing insulin sensitivity and in turn down regulating fatty acid synthase expression. (wikipedia.org)
  • amino
  • These enzymes are grouped into three classes based on their amino acid sequences, mechanism of reaction, method of catalysis and their structure. (wikipedia.org)
  • Like all proteins, the unique amino acid arrangement in the primary sequence of GLUT4 are what allow it to transport glucose across the plasma membrane. (wikipedia.org)
  • Fructose undergoes the Maillard reaction, non-enzymatic browning, with amino acids. (wikipedia.org)
  • hepatic
  • These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy. (wikipedia.org)
  • polypeptide
  • The hormone glucose-dependent insulinotropic polypeptide (GIP) is secreted from the earlier (proximal) part of the small intestine in lower amounts after isomaltulose than for sucrose ingestion, whereas the hormone glucagon-like peptide-1 (GLP-1) is secreted from later (distal) parts of the small intestine in higher amounts with isomaltulose compared with sucrose. (wikipedia.org)
  • insulin resistance
  • 6 ) provided provocative evidence that, indeed, myocardial lipid accumulation occurs in vivo in humans, specifically among individuals with DM and in those with insulin resistance. (onlinejacc.org)
  • Recent investigations have revealed that insulin resistance helps to conserve the brain's glucose supply by preventing muscles from taking up excessive glucose. (wikipedia.org)
  • In theory, insulin resistance should even be strengthened under harsh metabolic conditions such as pregnancy, during which the expanding fetal brain demands more glucose. (wikipedia.org)
  • factors related to stress, socio-economic status and history have been shown to activate the stress response, which increases the production of glucose and insulin resistance, as well as inhibiting pancreatic function and thus might be of importance, although it is not fully corroborated by the scientific evidence. (wikipedia.org)
  • thermogenesis
  • Adult humans have a substantial amount of inducible-brown (or beige) fat, which is associated with increased energy expenditure and reduced weight gain via thermogenesis. (springer.com)
  • Thus, although the presence of active BAT is correlated with cold-induced energy expenditure, direct measurement of MRO 2 indicates that BAT is a minor source of thermogenesis in humans. (pubmedcentralcanada.ca)
  • However, whether BAT contributes to cold-induced nonshivering thermogenesis in humans has not been proven. (jci.org)
  • In sum, our study provides evidence that BAT acts as a nonshivering thermogenesis effector in humans. (jci.org)
  • Glucose uptake in BAT is stimulated in two metabolic states: sympathetically stimulated during active thermogenesis or by insulin during active anabolic processes. (rupress.org)
  • Diabetes
  • Many insulin sensitizing drugs (namely, the thiazolidinediones) used in the treatment of diabetes activate PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion. (wikipedia.org)
  • serum
  • Most studies have shown relatively little difference in the fatty acid composition of the various fat stores including fat in serum [ 2 ]. (hindawi.com)
  • 4 ] reported that visceral fat thickness was positively correlated to levels of palmitic and saturate fatty acids in serum, but negatively correlated with levels of linoleic and polyunsaturated fatty acids. (hindawi.com)
  • Finally, in a trial of MR blockade in elderly humans, changes in serum miR-155 predicted the BP treatment response. (jci.org)
  • increases
  • As activity increases and it begins to pump faster, the cardiac muscles begin to oxidize glucose at a higher rate. (wikipedia.org)
  • As the vesicles fuse with the plasma membrane, GLUT4 transporters are inserted and become available for transporting glucose, and glucose absorption increases. (wikipedia.org)
  • GLUT4
  • At the cell surface, GLUT4 permits the facilitated diffusion of circulating glucose down its concentration gradient into muscle and fat cells. (wikipedia.org)
  • In order to increase glucose levels in the cell, GLUT4 is the primary transporter used in this facilitated diffusion. (wikipedia.org)
  • GLUT4, however, is still believed to be the primary transporter for glucose. (wikipedia.org)
  • Much like in other tissues, GLUT4 also responds to insulin signaling, and is transported into the plasma membrane to facilitate the diffusion of glucose into the cell. (wikipedia.org)
  • The genetically engineered muscle insulin receptor knock‐out (MIRKO) mouse was designed to be insensitive to glucose uptake caused by insulin, meaning that GLUT4 is absent. (wikipedia.org)
  • myocardial
  • In patients with acute myocardial infarction (AMI) and no history of T2DM, impaired glucose tolerance (IGT) and undiagnosed T2DM are common and strong predictors of poor prognosis ( 7 ). (diabetesjournals.org)
  • In humans, there are emerging yet limited data for myocardial lipid accumulation. (onlinejacc.org)
  • In coronary artery disease (CAD), glucose is an important source of energy and preserved myocardial glucose uptake is essential for the viability of jeopardized myocardium. (diabetesjournals.org)
  • Myocardial glucose uptake was measured with [ 18 F]fluoro-2-deoxy- d -glucose positron emission tomography in ischemic (evaluated by single-photon emission tomography and coronary angiography) and nonischemic regions during euglycemic-hyperinsulinemic clamp before and after a 16-week intervention period with rosiglitazone ( n = 27) or placebo ( n = 27). (diabetesjournals.org)
  • Rosiglitazone increased myocardial glucose uptake from 20.6 ± 11.8 to 25.5 ± 12.4 μmol · 100 g −1 · min −1 ( P = 0.038 vs. baseline, P = 0.023 vs. placebo) in ischemic regions and from 21.7 ± 12.1 to 28.0 ± 12.7 μmol · 100 g −1 · min −1 ( P = 0.014 vs. baseline, P = 0.003 vs. placebo) in nonischemic regions. (diabetesjournals.org)
  • The increase in myocardial glucose uptake was partly explained by the suppression of free fatty acid levels during clamp. (diabetesjournals.org)
  • Rosiglitazone therapy significantly increased insulin sensitivity and improved myocardial glucose uptake in type 2 diabetic patients with CAD. (diabetesjournals.org)
  • These results suggest that rosiglitazone therapy may facilitate myocardial glucose storage and utilization in these patients. (diabetesjournals.org)
  • It has been suggested that myocardial glucose uptake in type 2 diabetic and nondiabetic patients with and without coronary artery disease (CAD) is similar to that of healthy subjects ( 5 , 6 ). (diabetesjournals.org)
  • In some studies, myocardial glucose uptake has been noted to differ between groups ( 7 - 10 ). (diabetesjournals.org)
  • Furthermore, rosiglitazone treatment restores myocardial glucose uptake during ischemia and thus protects myocardium from ischemic injury ( 15 ). (diabetesjournals.org)
  • concentrations
  • Despite this potential, there has been little study defining POP concentrations in live human intra-abdominal fat. (hindawi.com)
  • This also means that muscle cells are able to take in more glucose as its intracellular concentrations decrease. (wikipedia.org)
  • triglycerides
  • It is a water-soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins (VLDL), into two free fatty acids and one monoacylglycerol molecule. (wikipedia.org)
  • There is also evidence suggesting that acylation stimulating protein (ASP) promotes the aggregation of triglycerides in adipose cells. (wikipedia.org)
  • adult humans
  • Recent studies using PET with 18F-fluorodeoxyglucose (18FDG) have shown the presence of BAT in adult humans. (jci.org)
  • inert
  • Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. (nature.com)
  • arachidonic acid
  • These agents include various polyunsaturated fatty acids like arachidonic acid and arachidonic acid metabolites such as certain members of the 5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid family, e.g. 5-oxo-15(S)-HETE and 5-oxo-ETE or 15-Hydroxyicosatetraenoic acid family including 15(S)-HETE, 15(R)-HETE, and 15(S)-HpETE. (wikipedia.org)
  • AdPLA catalyzes the rate-limiting step, production of arachidonic acid, for the production of prostaglandins, specifically prostaglandin E2 (PGE2). (wikipedia.org)
  • hydrolysis
  • Its primary enzymatic function is to catalyze the preferential hydrolysis of phosphatidylcholines at the sn-2 position, generating free fatty acids. (wikipedia.org)
  • Optimum AdPLA activity occurs in relatively basic conditions, between pH 7 and 9, to facilitate formation of a histidine-water complex and subsequent fatty acid hydrolysis. (wikipedia.org)
  • In humans, a majority of such exoenzymes can be found in the digestive system and are used for metabolic breakdown of macronutrients via hydrolysis. (wikipedia.org)