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The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis.

Saponaro C, Gaggini M, Carli F, Gastaldelli A - Nutrients (2015)

Bottom Line: Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle.This is now a recognized risk factor for the development of metabolic disorders, such as obesity, diabetes, fatty liver disease (NAFLD), cardiovascular diseases (CVD) and hepatocellular carcinoma (HCC).The causes for lipotoxicity are not only a high fat diet but also excessive lipolysis, adipogenesis and adipose tissue insulin resistance.

View Article: PubMed Central - PubMed

Affiliation: Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, via Moruzzi, 1 56124 Pisa, Italy. chiara.saponaro@gmail.com.

ABSTRACT
Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. This is now a recognized risk factor for the development of metabolic disorders, such as obesity, diabetes, fatty liver disease (NAFLD), cardiovascular diseases (CVD) and hepatocellular carcinoma (HCC). The causes for lipotoxicity are not only a high fat diet but also excessive lipolysis, adipogenesis and adipose tissue insulin resistance. The aims of this review are to investigate the subtle balances that underlie lipolytic, lipogenic and oxidative pathways, to evaluate critical points and the complexities of these processes and to better understand which are the metabolic derangements resulting from their imbalance, such as type 2 diabetes and non alcoholic fatty liver disease.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of lipolytic and lipogenic pathways. Triacyglycerol (TAG) synthesis requires the activation of free fatty acids (FFA) into Acyl-CoA by enzyme acyl-CoA synthetase. FFA-CoA and G3P are transformed via acylation, by glycerol-3-phosphate acyltransferase (GPAT) and acylCoA acylglycerol-3-phosphate acyltransferases (AGPAT), to phosphatidic acid (PA); then, after a dephosphorylation by phosphohydrolase (PAP2), diacylglycerols (DAG) are formed. Diacylglycerol acyltransferase (DGAT) catalyzes the conversion of DAG into TAG. In the adipocyte, G3P might come either from glycolysis or from non-carbohydrate substrates via the enzyme phosphoenolpyruvate carboxykinase (PEPCK), through a process named glyceroneogenesis. In the liver G3P can also be synthesized from plasma glycerol. De novo fatty acids synthesis (also referred to as de novo lipogenesis or DNL) occurs in the cytoplasm of various cells (e.g., adipocytes and hepatocytes) where citric acid is converted to acetyl-CoA by ATP-citrate lyase (ACL) and subsequently to malonyl-CoA by acetyl-CoA carboxylase (ACC). DNL occurs mainly in the liver, but it might occur in adipose tissue as well, although with low rates. This process requires the two enzymes ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC) and the multi-enzymatic complex fatty acid synthase (FAS). G3P can be synthesized directly from non-carbohydrate substrates such as pyruvate, lactate or amino acids in oxaloacetate, that is converted to G3P either directly from phoenolpyruvate (PEP), via the key enzyme phosphoenolpyruvate carboxykinase (PEPCK), or through synthesis of dihydroxyacetone (DHA). TAG catabolism (i.e., lipolysis) involves several lipases, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) and produces the release of three free fatty acids (FFA) and one glycerol molecule.
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nutrients-07-05475-f001: Schematic representation of lipolytic and lipogenic pathways. Triacyglycerol (TAG) synthesis requires the activation of free fatty acids (FFA) into Acyl-CoA by enzyme acyl-CoA synthetase. FFA-CoA and G3P are transformed via acylation, by glycerol-3-phosphate acyltransferase (GPAT) and acylCoA acylglycerol-3-phosphate acyltransferases (AGPAT), to phosphatidic acid (PA); then, after a dephosphorylation by phosphohydrolase (PAP2), diacylglycerols (DAG) are formed. Diacylglycerol acyltransferase (DGAT) catalyzes the conversion of DAG into TAG. In the adipocyte, G3P might come either from glycolysis or from non-carbohydrate substrates via the enzyme phosphoenolpyruvate carboxykinase (PEPCK), through a process named glyceroneogenesis. In the liver G3P can also be synthesized from plasma glycerol. De novo fatty acids synthesis (also referred to as de novo lipogenesis or DNL) occurs in the cytoplasm of various cells (e.g., adipocytes and hepatocytes) where citric acid is converted to acetyl-CoA by ATP-citrate lyase (ACL) and subsequently to malonyl-CoA by acetyl-CoA carboxylase (ACC). DNL occurs mainly in the liver, but it might occur in adipose tissue as well, although with low rates. This process requires the two enzymes ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC) and the multi-enzymatic complex fatty acid synthase (FAS). G3P can be synthesized directly from non-carbohydrate substrates such as pyruvate, lactate or amino acids in oxaloacetate, that is converted to G3P either directly from phoenolpyruvate (PEP), via the key enzyme phosphoenolpyruvate carboxykinase (PEPCK), or through synthesis of dihydroxyacetone (DHA). TAG catabolism (i.e., lipolysis) involves several lipases, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) and produces the release of three free fatty acids (FFA) and one glycerol molecule.

Mentions: The process of fatty acid esterification into TAG involves the activation of FFA into Acyl-CoA through the formation of monacylglycerol (MAG) and diacyglycerol (DAG) by reacting with glycerol-3-phosphate (G3P) (Figure 1). Several hormones control lipogenesis including insulin that stimulates lipid synthesis and adipogenesis, while glucagon and catecholamines promote acetyl-CoA carboxylase (ACC) phosphorylation and inhibit fatty acids (FA) synthesis. Sources of G3P and Acyl-CoA are plasma glycerol and FFA, but these substrates may also be synthesized de novo. The contribution of glyceroneogenesis and de novo lipogenesis to hepatic TG synthesis is significant, particularly in conditions of insulin resistance, and might be a target for drug intervention. Below we discuss the different pathways involved in lipogenesis and how they are altered in metabolic diseases, particularly NAFLD and type 2 diabetes (T2DM).


The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis.

Saponaro C, Gaggini M, Carli F, Gastaldelli A - Nutrients (2015)

Schematic representation of lipolytic and lipogenic pathways. Triacyglycerol (TAG) synthesis requires the activation of free fatty acids (FFA) into Acyl-CoA by enzyme acyl-CoA synthetase. FFA-CoA and G3P are transformed via acylation, by glycerol-3-phosphate acyltransferase (GPAT) and acylCoA acylglycerol-3-phosphate acyltransferases (AGPAT), to phosphatidic acid (PA); then, after a dephosphorylation by phosphohydrolase (PAP2), diacylglycerols (DAG) are formed. Diacylglycerol acyltransferase (DGAT) catalyzes the conversion of DAG into TAG. In the adipocyte, G3P might come either from glycolysis or from non-carbohydrate substrates via the enzyme phosphoenolpyruvate carboxykinase (PEPCK), through a process named glyceroneogenesis. In the liver G3P can also be synthesized from plasma glycerol. De novo fatty acids synthesis (also referred to as de novo lipogenesis or DNL) occurs in the cytoplasm of various cells (e.g., adipocytes and hepatocytes) where citric acid is converted to acetyl-CoA by ATP-citrate lyase (ACL) and subsequently to malonyl-CoA by acetyl-CoA carboxylase (ACC). DNL occurs mainly in the liver, but it might occur in adipose tissue as well, although with low rates. This process requires the two enzymes ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC) and the multi-enzymatic complex fatty acid synthase (FAS). G3P can be synthesized directly from non-carbohydrate substrates such as pyruvate, lactate or amino acids in oxaloacetate, that is converted to G3P either directly from phoenolpyruvate (PEP), via the key enzyme phosphoenolpyruvate carboxykinase (PEPCK), or through synthesis of dihydroxyacetone (DHA). TAG catabolism (i.e., lipolysis) involves several lipases, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) and produces the release of three free fatty acids (FFA) and one glycerol molecule.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663603&req=5

nutrients-07-05475-f001: Schematic representation of lipolytic and lipogenic pathways. Triacyglycerol (TAG) synthesis requires the activation of free fatty acids (FFA) into Acyl-CoA by enzyme acyl-CoA synthetase. FFA-CoA and G3P are transformed via acylation, by glycerol-3-phosphate acyltransferase (GPAT) and acylCoA acylglycerol-3-phosphate acyltransferases (AGPAT), to phosphatidic acid (PA); then, after a dephosphorylation by phosphohydrolase (PAP2), diacylglycerols (DAG) are formed. Diacylglycerol acyltransferase (DGAT) catalyzes the conversion of DAG into TAG. In the adipocyte, G3P might come either from glycolysis or from non-carbohydrate substrates via the enzyme phosphoenolpyruvate carboxykinase (PEPCK), through a process named glyceroneogenesis. In the liver G3P can also be synthesized from plasma glycerol. De novo fatty acids synthesis (also referred to as de novo lipogenesis or DNL) occurs in the cytoplasm of various cells (e.g., adipocytes and hepatocytes) where citric acid is converted to acetyl-CoA by ATP-citrate lyase (ACL) and subsequently to malonyl-CoA by acetyl-CoA carboxylase (ACC). DNL occurs mainly in the liver, but it might occur in adipose tissue as well, although with low rates. This process requires the two enzymes ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC) and the multi-enzymatic complex fatty acid synthase (FAS). G3P can be synthesized directly from non-carbohydrate substrates such as pyruvate, lactate or amino acids in oxaloacetate, that is converted to G3P either directly from phoenolpyruvate (PEP), via the key enzyme phosphoenolpyruvate carboxykinase (PEPCK), or through synthesis of dihydroxyacetone (DHA). TAG catabolism (i.e., lipolysis) involves several lipases, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) and produces the release of three free fatty acids (FFA) and one glycerol molecule.
Mentions: The process of fatty acid esterification into TAG involves the activation of FFA into Acyl-CoA through the formation of monacylglycerol (MAG) and diacyglycerol (DAG) by reacting with glycerol-3-phosphate (G3P) (Figure 1). Several hormones control lipogenesis including insulin that stimulates lipid synthesis and adipogenesis, while glucagon and catecholamines promote acetyl-CoA carboxylase (ACC) phosphorylation and inhibit fatty acids (FA) synthesis. Sources of G3P and Acyl-CoA are plasma glycerol and FFA, but these substrates may also be synthesized de novo. The contribution of glyceroneogenesis and de novo lipogenesis to hepatic TG synthesis is significant, particularly in conditions of insulin resistance, and might be a target for drug intervention. Below we discuss the different pathways involved in lipogenesis and how they are altered in metabolic diseases, particularly NAFLD and type 2 diabetes (T2DM).

Bottom Line: Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle.This is now a recognized risk factor for the development of metabolic disorders, such as obesity, diabetes, fatty liver disease (NAFLD), cardiovascular diseases (CVD) and hepatocellular carcinoma (HCC).The causes for lipotoxicity are not only a high fat diet but also excessive lipolysis, adipogenesis and adipose tissue insulin resistance.

View Article: PubMed Central - PubMed

Affiliation: Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, via Moruzzi, 1 56124 Pisa, Italy. chiara.saponaro@gmail.com.

ABSTRACT
Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. This is now a recognized risk factor for the development of metabolic disorders, such as obesity, diabetes, fatty liver disease (NAFLD), cardiovascular diseases (CVD) and hepatocellular carcinoma (HCC). The causes for lipotoxicity are not only a high fat diet but also excessive lipolysis, adipogenesis and adipose tissue insulin resistance. The aims of this review are to investigate the subtle balances that underlie lipolytic, lipogenic and oxidative pathways, to evaluate critical points and the complexities of these processes and to better understand which are the metabolic derangements resulting from their imbalance, such as type 2 diabetes and non alcoholic fatty liver disease.

No MeSH data available.


Related in: MedlinePlus