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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

Relationship insulin-lipolysis. As insulin concentration increases, lipolysis, and thus plasma free fatty acids (FFA) concentration, is suppressed following a non-linear curve [65,69,70]. In presence of insulin resistance the curve is shifted to the right indicating that for the same insulin levels lipolysis is less suppressed and circulating FFA levels are higher. The product FFA × Insulin is used as an index of adipose tissue-insulin resistance.
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nutrients-07-05475-f003: Relationship insulin-lipolysis. As insulin concentration increases, lipolysis, and thus plasma free fatty acids (FFA) concentration, is suppressed following a non-linear curve [65,69,70]. In presence of insulin resistance the curve is shifted to the right indicating that for the same insulin levels lipolysis is less suppressed and circulating FFA levels are higher. The product FFA × Insulin is used as an index of adipose tissue-insulin resistance.

Mentions: Insulin resistance is often present at the levels of all organs, muscle, liver, heart and adipose tissue, where insulin promotes FA esterification and synthesis of TAG. In addition, insulin suppresses adipose tissue lipolysis and the release of free fatty acid (FFA). The dose-response curve of FFA vs. insulin follows a hyperbolic curve [65]. As subjects become more insulin resistant at the level of adipose tissue the curve shifts to the right indicating that for the same insulin levels plasma FFA are higher (Figure 3). In this condition elevated plasma FFA reduce basal and insulin-stimulated muscle glucose uptake by inhibiting insulin signaling [9]. FFA decrease muscle ATP synthesis [66] and nitric oxide production [67], and impair insulin-stimulated activation of phosphoinositol-3 kinase (PI3K), pyruvate dehydrogenase kinase-isozyme 1 (PDK1), RAC-alpha serine/threonine-protein kinase (also known as proto-oncogene c-AKT), and endothelial nitric oxide synthase (eNOS) [67]. Moreover, high FFA are associated with increased cellular levels of diacylglycerol (DAG), the first step of TAG synthesis (Figure 1). Other lipid metabolites are increased in insulin resistant states, e.g., ceramide, and long-chain fatty acyl-coenzyme A (CoA), and activate transcription factors such as nuclear factor-κB (NF-κB) and inflammatory processes [68].


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

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

Relationship insulin-lipolysis. As insulin concentration increases, lipolysis, and thus plasma free fatty acids (FFA) concentration, is suppressed following a non-linear curve [65,69,70]. In presence of insulin resistance the curve is shifted to the right indicating that for the same insulin levels lipolysis is less suppressed and circulating FFA levels are higher. The product FFA × Insulin is used as an index of adipose tissue-insulin resistance.
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-07-05475-f003: Relationship insulin-lipolysis. As insulin concentration increases, lipolysis, and thus plasma free fatty acids (FFA) concentration, is suppressed following a non-linear curve [65,69,70]. In presence of insulin resistance the curve is shifted to the right indicating that for the same insulin levels lipolysis is less suppressed and circulating FFA levels are higher. The product FFA × Insulin is used as an index of adipose tissue-insulin resistance.
Mentions: Insulin resistance is often present at the levels of all organs, muscle, liver, heart and adipose tissue, where insulin promotes FA esterification and synthesis of TAG. In addition, insulin suppresses adipose tissue lipolysis and the release of free fatty acid (FFA). The dose-response curve of FFA vs. insulin follows a hyperbolic curve [65]. As subjects become more insulin resistant at the level of adipose tissue the curve shifts to the right indicating that for the same insulin levels plasma FFA are higher (Figure 3). In this condition elevated plasma FFA reduce basal and insulin-stimulated muscle glucose uptake by inhibiting insulin signaling [9]. FFA decrease muscle ATP synthesis [66] and nitric oxide production [67], and impair insulin-stimulated activation of phosphoinositol-3 kinase (PI3K), pyruvate dehydrogenase kinase-isozyme 1 (PDK1), RAC-alpha serine/threonine-protein kinase (also known as proto-oncogene c-AKT), and endothelial nitric oxide synthase (eNOS) [67]. Moreover, high FFA are associated with increased cellular levels of diacylglycerol (DAG), the first step of TAG synthesis (Figure 1). Other lipid metabolites are increased in insulin resistant states, e.g., ceramide, and long-chain fatty acyl-coenzyme A (CoA), and activate transcription factors such as nuclear factor-κB (NF-κB) and inflammatory processes [68].

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