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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

Pathways of β-oxidation. β-oxidation is the catabolic pathway that occurs in mitochondria and produces energy from TG hydrolysis. (1) FFA are transformed to Acyl-CoA in cytosol; (2) protein Carnitine Palmitoyl Transferase-1 (CPT1) catalizes the transfer of the acyl group of a long-chain fatty acyl-CoA to carnitine to form acylcarnitines (mainly Palmitoylcarnitine); (3) Carnitine Acyltranferase (CACT) transfers acylcarnitine across outer mitochondrial membrane; (4) Carnitine Palmitoyl Transferase-2 (CPT2) reconverts acylcarnitine in acylCoA and carnitine; (5) Acyl-CoA enters in β-oxidation cycle and is degraded in several Acetyl-CoA molecules; (6) Acetyl-CoA enters in Krebs cycle to produce energy as Adenosine Triphosphate (ATP).
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nutrients-07-05475-f005: Pathways of β-oxidation. β-oxidation is the catabolic pathway that occurs in mitochondria and produces energy from TG hydrolysis. (1) FFA are transformed to Acyl-CoA in cytosol; (2) protein Carnitine Palmitoyl Transferase-1 (CPT1) catalizes the transfer of the acyl group of a long-chain fatty acyl-CoA to carnitine to form acylcarnitines (mainly Palmitoylcarnitine); (3) Carnitine Acyltranferase (CACT) transfers acylcarnitine across outer mitochondrial membrane; (4) Carnitine Palmitoyl Transferase-2 (CPT2) reconverts acylcarnitine in acylCoA and carnitine; (5) Acyl-CoA enters in β-oxidation cycle and is degraded in several Acetyl-CoA molecules; (6) Acetyl-CoA enters in Krebs cycle to produce energy as Adenosine Triphosphate (ATP).

Mentions: The most important catabolic pathway for TAG and FA degradation is β-oxidation that occurs in mitochondria and produces the energy for homeostasis of cells and tissues (Figure 5). The oxidation of fatty acids occurs in particular during fasting state and carbohydrate starvation. In liver mitochondria, the acetyl-CoA produced during β-oxidation is converted to ketone bodies, i.e., acetoacetate, beta-hydroxybutyrate (BOH), and acetone. Ketone bodies are released and then taken up by other tissues such as the brain, muscle or heart where they are converted back to acetyl-CoA to serve as an energy source. Patients with fatty liver not only have increased VLDL-TG synthesis [43,44], but also increased β-oxidation and release of BOH [69]. However, obesity is also associated with increased levels of β-oxidation by the muscles and heart due to elevated circulating concentrations of FFAs that activate PPAR-α.


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

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

Pathways of β-oxidation. β-oxidation is the catabolic pathway that occurs in mitochondria and produces energy from TG hydrolysis. (1) FFA are transformed to Acyl-CoA in cytosol; (2) protein Carnitine Palmitoyl Transferase-1 (CPT1) catalizes the transfer of the acyl group of a long-chain fatty acyl-CoA to carnitine to form acylcarnitines (mainly Palmitoylcarnitine); (3) Carnitine Acyltranferase (CACT) transfers acylcarnitine across outer mitochondrial membrane; (4) Carnitine Palmitoyl Transferase-2 (CPT2) reconverts acylcarnitine in acylCoA and carnitine; (5) Acyl-CoA enters in β-oxidation cycle and is degraded in several Acetyl-CoA molecules; (6) Acetyl-CoA enters in Krebs cycle to produce energy as Adenosine Triphosphate (ATP).
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-07-05475-f005: Pathways of β-oxidation. β-oxidation is the catabolic pathway that occurs in mitochondria and produces energy from TG hydrolysis. (1) FFA are transformed to Acyl-CoA in cytosol; (2) protein Carnitine Palmitoyl Transferase-1 (CPT1) catalizes the transfer of the acyl group of a long-chain fatty acyl-CoA to carnitine to form acylcarnitines (mainly Palmitoylcarnitine); (3) Carnitine Acyltranferase (CACT) transfers acylcarnitine across outer mitochondrial membrane; (4) Carnitine Palmitoyl Transferase-2 (CPT2) reconverts acylcarnitine in acylCoA and carnitine; (5) Acyl-CoA enters in β-oxidation cycle and is degraded in several Acetyl-CoA molecules; (6) Acetyl-CoA enters in Krebs cycle to produce energy as Adenosine Triphosphate (ATP).
Mentions: The most important catabolic pathway for TAG and FA degradation is β-oxidation that occurs in mitochondria and produces the energy for homeostasis of cells and tissues (Figure 5). The oxidation of fatty acids occurs in particular during fasting state and carbohydrate starvation. In liver mitochondria, the acetyl-CoA produced during β-oxidation is converted to ketone bodies, i.e., acetoacetate, beta-hydroxybutyrate (BOH), and acetone. Ketone bodies are released and then taken up by other tissues such as the brain, muscle or heart where they are converted back to acetyl-CoA to serve as an energy source. Patients with fatty liver not only have increased VLDL-TG synthesis [43,44], but also increased β-oxidation and release of BOH [69]. However, obesity is also associated with increased levels of β-oxidation by the muscles and heart due to elevated circulating concentrations of FFAs that activate PPAR-α.

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