Intramuscular fat

Last updated August 06, 2019

Intramuscular fat (also known as intramuscular triglycerides, intramuscular triacylglycerol, or intramyocellular triacylglycerol [IMTG]) is located inside skeletal muscle fibers. It is stored in lipid droplets that exist in close proximity to the mitochondria, where it serves as an energy store that can be used during exercise. In humans, excess accumulation of intramuscular fat has been associated with conditions such as insulin resistance and type 2 diabetes. The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with over-accumulation of intramuscular fat, which may contribute to AIDS wasting syndrome.

Skeletal muscle is one of three major muscle types, the others being cardiac muscle and smooth muscle. It is a form of striated muscle tissue, which is under the voluntary control of the somatic nervous system. Most skeletal muscles are attached to bones by bundles of collagen fibers known as tendons.

Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin.

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, and unexplained weight loss. Symptoms may also include increased hunger, feeling tired, and sores that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

Diabetes

Increased IMTG was once thought responsible for increased insulin resistance. However, the discovery that athletes as well as obese individuals have high IMTG levels confounded these findings. Instead, IMTG metabolites, such as diacylglycerol and ceramide are responsible for the insulin resistance. Studies demonstrating the effects of IMTGs show that the mechanism involves the activation of the protein kinase C theta, which promotes the phosphorylation of IRS-1, thereby inhibiting the insulin signaling cascade.

A metabolite is the intermediate end product of metabolism. The term metabolite is usually restricted to small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, catalytic activity of their own, defense, and interactions with other organisms. A primary metabolite is directly involved in normal "growth", development, and reproduction. Ethylene is an example of a primary metabolite produced in large-scale by industrial microbiology. A secondary metabolite is not directly involved in those processes, but usually has an important ecological function. Examples include antibiotics and pigments such as resins and terpenes etc. Some antibiotics use primary metabolites as precursors, such as actinomycin which is created from the primary metabolite, tryptophan. Some sugars are metabolites, such as fructose or glucose, which are both present in the metabolic pathways.

Ceramide compound from a family of lipid compounds

Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells.

Protein Biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

Insulin Resistance

Increased plasma free-fatty acid levels and increased accumulation of IMTG correlate well with insulin resistance in muscles. However, athletes often do not exhibit this correlation since they are typically insulin sensitive, while expressing high levels of IMTG. Researchers believe that the improved efficiency of trained skeletal muscles prevents the development of insulin resistance.^[1]

Fatty acid carboxylic acid with a long aliphatic chain, which is either saturated or unsaturated

In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with a long aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually not found in organisms, but instead as three main classes of esters: triglycerides, phospholipids, and cholesterol esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and they are important structural components for cells.

Exercise

Intramuscular triacylglycerol serves as an energy store that can be used during exercise, when it may contribute up to 20% of total energy turnover (depending on diet, gender, and exercise type).^[2]

Scientists think that a low-calorie diet and exercise-induced proteins (Sterol regulatory element-binding protein) cause the high levels of IMTG in athletes' skeletal muscle. In contrast, the build-up of IMTG in obese individuals correlates to high levels of adipose tissue.^[3]

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes SREBF1 and SREBF2. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes. In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences, thus upregulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative feed back loop.

Women have a higher IMTG content and studies have revealed that they use more IMTGs during exercise.^[4]

Related Research Articles

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Leptin protein-coding gene in the species Homo sapiens

Leptin is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance by inhibiting hunger, which in turn diminishes fat storage in adipocytes. Leptin acts on cell receptors in the arcuate nucleus of the hypothalamus.

Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolyzed into a glycerol and three fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in fat adipocytes. Lipolysis is induced by several hormones, including glucagon, epinephrine, norepinephrine, growth hormone, atrial natriuretic peptide, brain natriuretic peptide, and cortisol.

Brown adipose tissue (BAT) or brown fat makes up the adipose organ together with white adipose tissue. Brown adipose tissue is found in almost all mammals.

5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low. It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 and SnRK1 in yeast and plants, respectively. It consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans. It is expressed in a number of tissues, including the liver, brain, and skeletal muscle. In response to binding AMP and ADP, the net effect of AMPK activation is stimulation of hepatic fatty acid oxidation, ketogenesis, stimulation of skeletal muscle fatty acid oxidation and glucose uptake, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipogenesis, activation of adipocyte lipolysis, and modulation of insulin secretion by pancreatic beta-cells.

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Glycogen synthase is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase that catalyses the reaction of UDP-glucose and _n to yield UDP and _n+1.

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. GLUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle. The first evidence for this distinct glucose transport protein was provided by David James in 1988. The gene that encodes GLUT4 was cloned and mapped in 1989.

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Diacylglycerol O-acyltransferase 2 is a protein that in humans is encoded by the DGAT2 gene.

References

↑ Timmermans R, Saris W, van Loon L (2006). "[Insulin resistance: the role of intramuscular triglyceride and the importance of physical activity]". Ned Tijdschr Geneeskd. 150 (3): 122–7. PMID 16463611.
↑ Roepstorff C, Vistisen B, Kiens B (2005). "Intramuscular triacylglycerol in energy metabolism during exercise in humans". Exerc Sport Sci Rev. 33 (4): 182–8. doi:10.1097/00003677-200510000-00006. PMID 16239835.
↑ Nadeau K, Ehlers L, Aguirre L, Moore R, Jew K, Ortmeyer H, Hansen B, Reusch J, Draznin B (2006). "Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle". Am J Physiol Endocrinol Metab. 291 (1): E90–8. doi:10.1152/ajpendo.00543.2005. PMID 16449296.
↑ Roepstorff C, Donsmark M, Thiele M, Vistisen B, Stewart G, Vissing K, Schjerling P, Hardie D, Galbo H, Kiens B (2006). "Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise". Am J Physiol Endocrinol Metab. 291 (5): E1106–14. doi:10.1152/ajpendo.00097.2006. PMID 16822962.

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[1] Timmermans R, Saris W, van Loon L (2006). "[Insulin resistance: the role of intramuscular triglyceride and the importance of physical activity]". Ned Tijdschr Geneeskd. 150 (3): 122–7. PMID 16463611.

[2] Roepstorff C, Vistisen B, Kiens B (2005). "Intramuscular triacylglycerol in energy metabolism during exercise in humans". Exerc Sport Sci Rev. 33 (4): 182–8. doi:10.1097/00003677-200510000-00006. PMID 16239835.

[3] Nadeau K, Ehlers L, Aguirre L, Moore R, Jew K, Ortmeyer H, Hansen B, Reusch J, Draznin B (2006). "Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle". Am J Physiol Endocrinol Metab. 291 (1): E90–8. doi:10.1152/ajpendo.00543.2005. PMID 16449296.

[4] Roepstorff C, Donsmark M, Thiele M, Vistisen B, Stewart G, Vissing K, Schjerling P, Hardie D, Galbo H, Kiens B (2006). "Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise". Am J Physiol Endocrinol Metab. 291 (5): E1106–14. doi:10.1152/ajpendo.00097.2006. PMID 16822962.