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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

Effects of increased lipolysis on liver dysfunction. Excess lipolysis results in high free fatty acid (FFA) flux into the liver, where FFAs cause steatosis and exert lipotoxic effects. Triglycerides (TAG) synthetized in the liver are secreted into the plasma circulation as very low density lipoproteins (VLDL) causing dyslipidemia. Visceral fat has a preferential role in hepatic fat accumulation since released FFA reach the liver via the portal vein. Also increased hepatic de novo lipogenesis (DNL), inflammation and oxidative stress contribute to liver damage and hepatocyte dysfunction.
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nutrients-07-05475-f002: Effects of increased lipolysis on liver dysfunction. Excess lipolysis results in high free fatty acid (FFA) flux into the liver, where FFAs cause steatosis and exert lipotoxic effects. Triglycerides (TAG) synthetized in the liver are secreted into the plasma circulation as very low density lipoproteins (VLDL) causing dyslipidemia. Visceral fat has a preferential role in hepatic fat accumulation since released FFA reach the liver via the portal vein. Also increased hepatic de novo lipogenesis (DNL), inflammation and oxidative stress contribute to liver damage and hepatocyte dysfunction.

Mentions: Contribution of DNL to the TAG pool is crucial in the balance between lipolysis and lipogenesis; however, the contribution of DNL to TAG synthesis is still unknown, mainly because it is difficult to measure it in vivo in humans. Published data indicate that increased DNL rates contribute to excess hepatic TAG synthesis and deposition, causing NAFLD [20]. The rate of de novo synthesis of palmitate in humans has been measured using the deuterated water technique [20]. DNL contributes to 10%–35% of the total VLDL-TG pool [21], being higher in overweight compared to lean subjects and in general in insulin resistant states, including NAFLD [20,22,23,24]. Moreover, higher rates of DNL are associated with high postprandial glucose and insulin concentrations [21,25], inflammation, oxidative stress and macrophage infiltration [26] (Figure 2).


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

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

Effects of increased lipolysis on liver dysfunction. Excess lipolysis results in high free fatty acid (FFA) flux into the liver, where FFAs cause steatosis and exert lipotoxic effects. Triglycerides (TAG) synthetized in the liver are secreted into the plasma circulation as very low density lipoproteins (VLDL) causing dyslipidemia. Visceral fat has a preferential role in hepatic fat accumulation since released FFA reach the liver via the portal vein. Also increased hepatic de novo lipogenesis (DNL), inflammation and oxidative stress contribute to liver damage and hepatocyte dysfunction.
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-07-05475-f002: Effects of increased lipolysis on liver dysfunction. Excess lipolysis results in high free fatty acid (FFA) flux into the liver, where FFAs cause steatosis and exert lipotoxic effects. Triglycerides (TAG) synthetized in the liver are secreted into the plasma circulation as very low density lipoproteins (VLDL) causing dyslipidemia. Visceral fat has a preferential role in hepatic fat accumulation since released FFA reach the liver via the portal vein. Also increased hepatic de novo lipogenesis (DNL), inflammation and oxidative stress contribute to liver damage and hepatocyte dysfunction.
Mentions: Contribution of DNL to the TAG pool is crucial in the balance between lipolysis and lipogenesis; however, the contribution of DNL to TAG synthesis is still unknown, mainly because it is difficult to measure it in vivo in humans. Published data indicate that increased DNL rates contribute to excess hepatic TAG synthesis and deposition, causing NAFLD [20]. The rate of de novo synthesis of palmitate in humans has been measured using the deuterated water technique [20]. DNL contributes to 10%–35% of the total VLDL-TG pool [21], being higher in overweight compared to lean subjects and in general in insulin resistant states, including NAFLD [20,22,23,24]. Moreover, higher rates of DNL are associated with high postprandial glucose and insulin concentrations [21,25], inflammation, oxidative stress and macrophage infiltration [26] (Figure 2).

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