This article is excerpted from "Regulatoryroles for L-arginine in reducing white adipose tissue", Frontiers in Bioscience, 2012. Organized by He Weijie, Asia-Pacific Ministry of Science and Technology.
Abstract
As a nitrogen precursor substance of nitric oxide (NO), arginine regulates metabolic pathways of various substances such as fatty acids, glucose, amino acids, and proteins by means of cell signaling and gene expression. Specifically, arginine promotes lipolysis and activates the oxidation of fatty acids to CO2 and water by activating the expression of key genes. Potential mechanisms include increased expression of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), promotion of mitochondrial biogenesis, and growth of brown adipose tissue. Moreover, arginine regulates adipocyte-muscle cross-linking and energy distribution through the secretion of cytokines and hormones. In addition, arginine enhances the expression and activity of AMP-activated protein kinase (AMPK), thereby modulating lipid metabolism and energy balance. White fat cells are the main site for excess energy storage and are present in the form of triacylglycerols. There is increasing evidence that dietary supplementation with arginine is effective in reducing white body fat content in Zucker diabetic obese rats, diet-induced obese rats, growing fattening pigs, and obese type II diabetic patients. Therefore, arginine can be used to prevent and treat obesity as well as related metabolic syndrome.
1 Foreword
Human obesity or overweight is becoming more and more popular worldwide, and too much white fat deposition has become a burden on livestock in the market. When dietary energy intake is insufficient relative to the body's own needs, white adipose tissue provides non-esterified fatty acids through skeletal muscle and other organs through lipid breakdown. However, when dietary energy intake exceeds overall energy expenditure, fat builds up in white adipose tissue, leading to obesity and other health problems. Therefore, many researchers are studying lipid metabolism and energy distribution to prevent and treat obesity and related diseases.
More and more animal studies have shown that Arg plays an important role in regulating the metabolism of energy substances. Arg is synthesized from citrulline in almost all cells. In most mammals, including humans, pigs, and rats, citrulline is produced from glutamine, glutamic acid, and valine by using pyrroline-5-carboxylic acid as an intermediate. Although arginine is not an essential amino acid in the traditional sense to maintain the nitrogen balance of adult animals, arginine is now recognized as a nutritional and physiological requirement for maintaining cardiovascular health and reproductive function, both in males and females. of. It is worth noting that the addition of arginine to the diet of growing-finishing pigs can significantly increase skeletal muscle and intramuscular fat content while reducing body fat. These studies indicate that Arg regulates lipid and protein metabolism in a specific tissue manner.
2 Effects of arginine on lipid metabolism and energy distribution
2.1 The regulation of arginine on fat deposition
   The white adipose tissue deposits of the body are determined by the balance of fat production and decomposition. Increasing lipid breakdown or reducing fatty acid synthesis or both can reduce body fat deposition. A large number of in vitro tests have shown that arginine stimulates lipolysis of fat cells and promotes oxidation of long-chain fatty acids in insulin-sensitive tissues.
The response of fat cells to Arg's lipogenesis may depend strictly on cell type and cell differentiation stage.
In growing and finishing pigs, we found that adding 1% arginine can reduce fat deposition and promote protein synthesis throughout the body. In addition, arginine increased the ratio of intramuscular fat to steroidal skeletal muscle and reduced carcass fat content relative to the control group (Table 1). The results of nuclear magnetic resonance (NMR) metabolomics analysis showed that the protein synthesis increased and the fat deposition decreased in the arginine treatment group, and the nitrogen concentration in the serum and the lipid signal molecules changed accordingly. We also found that arginine can differentially regulate the expression of fat metabolism genes in skeletal muscle and adipose tissue, which is beneficial to the synthesis of skeletal muscle fat and the decomposition of white adipose tissue. Specifically, arginine down-regulates the expression of lipogenic genes, such as lipoprotein lipase (LPL) and acetyl-CoA carboxylase (ACC) alpha, but upregulates white adipose tissue including hormone-sensitive lipase (HSL). Expression of a lipolytic gene. In the porcine skeletal muscle of the arginine-treated group, LPL activity and the ratio of FAS mRNA and HSL mRNA were enhanced, resulting in an increase in intramuscular fat content. In addition, reduced expression of GLUT4 in porcine adipose tissue in the arginine-treated group was sufficient to reduce glucose transport and fatty acid synthesis, indicating that the energy metabolism substrate was preferentially partitioned into skeletal muscle rather than white adipose tissue.
2.2 The role of Arg-NO pathway in lipid metabolism
Arg can be converted to NO by NO synthase (NOS) in almost all mammalian cells, and the increase in extracellular Arg levels from 0.1 to 5 mM increases NO synthesis in different cell types including skeletal muscle and adipose tissue. In addition to NO, Arg may regulate mTOR cell signaling, thereby increasing and inhibiting protein synthesis.
2.3Arg and mitochondrial biosynthesis
Mitochondria play a key role in regulating lipid metabolism and fat breakdown in adipocytes. PGC-1α is a key nuclear receptor coactivator that induces mitochondrial biogenesis and is critical for regulating the quantity and quality of mitochondria, fatty acid oxidation, and heat production. Increased expression of PGC-1α promotes oxidation of long-chain fatty acids in adipocytes. NO is a mitochondrial regulator in the PGC-1α-dependent mechanism. Dietary supplementation with Arg increases the number and quality of mitochondria in adult rats.
2.4 Arg endocrine effect
Increased plasma Arg levels are associated with changes in the secretion of various cytokines (interleukin-6, interleukin-1β, interferon-gamma and tumor necrosis factor-alpha) and hormones (leptin, adiponectin, insulin and growth hormone). These cytokines and hormones in turn may affect insulin sensitivity, glucose homeostasis, and lipid metabolism. These mechanisms may be responsible for the direct choline action of arginine, membrane depolarization, calcium flux, and NO signaling.
2.5 The role of AMPK signaling pathway in lipid metabolism
AMPK is an important regulator of lipid metabolism and energy balance, activated by an increase in intracellular AMP/ATP ratio. Activation of AMPK activates the production of ATP metabolic pathways while inhibiting the synthesis. Therefore, AMPK signaling is critical for the regulation of fatty acid oxidation in the liver and skeletal muscle as well as mitochondrial biosynthesis, glucose uptake, and insulin sensitivity control in skeletal muscle.
3 Summary of
Biochemical and molecular biology studies have shown that the addition of arginine to the diet of young animals enhances dietary and metabolic energy to promote skeletal muscle growth rather than storage in adipose tissue. Therefore, supplementation with arginine is beneficial: a) reduce obesity in humans and animals; b) increase muscle mass in the corpus callosum and reduce fat accumulation, and improve the economics of animal husbandry. In the future, L-arginine, which has great potential, will certainly improve the health of humans and animals and improve the production efficiency of animals.
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