Glossary

Gary D. Lopaschuk

Acetyl-coenzyme A carboxylase (ACC) 2
Acetyl-coenzyme A carboxylase (ACC) is a key enzyme involved in both the synthesis and metabolism of fatty acids. ACC produces malonyl coenzyme A, which is both a substrate for fatty acid biosynthesis and a potent inhibitor of mitochondrial fatty acid uptake. Heart and muscle primarily express ACC2, which is the isoform of ACC that is thought to be primarily involved in the regulation of fatty acid oxidation.

Acylation stimulating protein (ASP)
Acylation stimulating protein (ASP) is an adipocyte-derived protein that upregulates triacylglycerol synthesis in adipocytes. ASP has recently been suggested to play an important role in the regulation of lipoprotein metabolism and triacylglycerol storage. ASP also appears to have role in the regulation of energy balance.

Adipophilin
Adipophilin is a protein that is involved in lipid transport or storage. Adipophilin, which was initially described in adipocytes, is associated with lipid accumulation in cells. It is found in many cells and may be a new marker for the identification of specialized differentiated cells containing lipid droplets and for diseases associated with fat-accumulating cells.

Adipsin
Adipsin is one of a number of physiologically important proteins excreted by adipocytes. Adipsin has a role in the regulation of energy intake and storage, and works with acylation stimulating protein to regulate lipoprotein metabolism and triacylglycerol storage. In the gut, adipsin facilitates removal of lipid from chylomicrons.

Agouti protein
Agouti protein is an endogenous antagonist of melanocortin receptors that have been implicated as part of the hypothalamic mechanism that mediates leptin-induced hypophagia. The agouti protein has a role in controlling energy homeostasis and possibly human pigmentation.

Angiotensinogen
The renin-angiotensin system is widely known for its importance in controlling blood pressure, electrolyte homeostasis, and volume regulation. Angiotensinogen is an early intermediate of this pathway, and polymorphisms in this gene contribute to the pathogenesis of both hypertension and cardiovascular disease.

Apolipoprotein (apo) E
Apolipoprotein (apo) E is one of the proteins associated with circulating lipoproteins.
Polymorphisms in the apo E gene result in the development of atherosclerosis and increase the risk for heart disease, stroke, and Alzheimer’s disease.

Cholesterol ester transfer protein (CETP)
Cholesterol ester transfer protein (CETP) facilitates reverse cholesterol transport from high-density lipoprotein (HDL) to triacylglycerol-rich lipoproteins. High plasma levels of CETP are correlated with low HDL cholesterol levels, a strong risk factor for coronary artery
disease.

Cytokines
Cytokines refer to a group of compounds that are produced under a variety of conditions, including during immune response and inflammatory reactions. Tumor necrosis
factor-a and interleukin-1 are examples of two cytokines.

Glucocorticoids
Glucocorticoids are steroids produced by the adrenal gland that have diverse actions on the body, including control of glucose metabolism, and control gene expression. Glucocorticoids regulate the transcription of a large number of genes, including a number of gluconeogenic genes in the liver.

Inducible nitric oxide synthase (iNOS)
Nitric oxide synthase (NOS) is the enzyme responsible for synthesizing nitric oxide (NO). NO has received considerable research attention, since it is not only a vasodilator but is also important in numerous other processes, including apoptosis. Inducible NOS (iNOS) is an isoform of NOS that can be dramatically induced under a variety of conditions. One example of this is the dramatic expression of iNOS in muscle following sepsis.

Insulin receptor substrate (IRS)-1
Insulin receptor substrate (IRS)-1 is a key protein in the insulin-signaling pathway. Binding of insulin to the receptor results in activation of IRS-1. IRS-1 then alters the activity of a number of downstream signaling pathways to mediate the diverse effects of insulin.

Interleukin-6 (IL-6)
Interleukin-6 (IL-6) is a proinflammatory cytokine involved in many immune responses, including physiological stress reactions. IL-6 is also involved in several diseases, including lymphoid malignancies. This cytokine binds to soluble IL-6 receptor circulating in blood, leading to signal transduction. A significant correlation between circulating IL-6 level and insulin sensitivity has recently been found in humans.

Leptin
Leptin is secreted from adipocytes and is thought to enter the brain to regulate and coordinate metabolism, feeding behavior, energy balance, and reproduction. There are many additional sites of leptin production (including human placenta, ovary, stomach, skeletal muscle, mammary gland, pituitary gland, and brain), as well as sites of peripheral leptin action, including muscle and heart.

Lipin
Lipin is the product of the gene that is mutated in fatty liver dystrophy. Mice with this mutation exhibit several phenotypic abnormalities, including hyperlipidemia, defects in adipocyte differentiation, impaired glucose tolerance, and slow growth.

Lipogenesis
Lipogenesis is a term describing the synthesis of lipids. It occurs primarily in the liver and adipocytes.

Lipoprotein lipase (LPL)
Lipoprotein lipase (LPL) is an enzyme that cleaves fatty acids from triacylglycerol contained within lipoproteins, with the subsequent release of fatty acids. LPL associated with the endothelium is a major source of fatty acids for both heart and skeletal muscle.

Mitogen-activated protein kinase (MAPK)
Mitogen-activated protein kinase (MAPK) is one of the kinases in the MAPK superfamily. This kinase pathway is engaged by phosphorylation in response to environmental stress signals and has many cellular actions, including a role in cell proliferation.

Monobutyrin
Monobutryin is a novel angiogenic compound that is synthesized and secreted during the differentiation of adipocytes. It has a major role as a differentiation-dependent angiogenic molecule.

Phosphatidylinositol 3-kinase
Phosphatidylinositol 3-kinase is an intracellular kinase activated by lipids that phosphorylates the cellular phospholipid, phosphatidylinositol. The product of this reaction is involved in many intracellular signaling pathways, including the control of energy metabolism.

Plasminogen activator inhibitor (PAI)-1
Plasminogen activator inhibitor (PAI)-1 is a protein that inhibits fibrinolysis and proteolysis. Increases in PAI-1 levels have been associated with increased risk of myocardial infarction and decreased risk of cerebrovascular events.

Resistin
Resistin is an adipose tissue-specific factor which is reported to induce insulin resistance, linking diabetes to obesity.

Triacylglycerol
Triacylglycerol is the major storage form of fatty acids in the body and consists of three fatty acids attached to a glycerol backbone. Fatty acid storage in adipocytes primarily occurs in the form of triacylglycerol. The heart also contains sizable triacylglycerol stores as a source of fatty acids for energy production.

Tumor necrosis factor-a (TNFa)
Tumor necrosis factor-a (TNFa) is a cytokine that has diverse actions in the body. TNFa binds to cardiac receptors and mediates a number of cellular processes, including the promotion of apoptosis (programmed cell death), and activation of inducible nitric oxide synthase.