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Human fat cell lipolysis: Biochemistry, regulation and clinical role

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Release of fatty acids (FAs) from adipose tissue through lipolysis in fat cells is a key event in many processes. FAs are not only energy substrates but also signalling molecules and substrates for lipoprotein production by the liver. Fat cells consist of>95% triglycerides that are hydrolysed during lipolysis to glycerol and FAs. The major rate-limiting factor for lipolysis is hormone-sensitive lipase, but additional lipases such as adipose tissue triglyceride lipase may also play a role. The regulation of human fat cell lipolysis is, in many ways, species unique. Only catecholamines, insulin and natriuretic peptides have pronounced acute effects. Catecholamines influence lipolysis through four different adrenoceptor subtypes, in contrast to rodents where only one subtype (β3) is of major importance. There are regional variations in adipocyte lipolysis leading to more release of FAs from the visceral than subcutaneous adipose tissue during hormone stimulation (insulin, catecholamines). Since, only visceral fat is linked to the liver (by the portal vein), alterations in visceral adipocyte tissue lipolysis have direct effects on the liver through portal FA release. The regional variations in lipolysis are further enhanced in obesity and polycystic ovarian syndrome, and are of importance for dyslipidaemia, hyperinsulinaemia and glucose intolerance in these conditions. There is a marked elevation of circulating FA levels among the obese, which may be due to enhanced production of tumour necrosis factor alpha in adipose tissue. This cytokine stimulates lipolysis through so-called MAP kinases. Pharmacological agents in clinical practice such as nicotinic acid and glitazones exert lipid-lowering and glucose-lowering effects, respectively, by decreasing FA output from the adipose tissue. This review covers the biochemistry, regulation and clinical aspects of human fat cell lipolysis.

Section snippets

Biochemistry of lipolysis

Fat droplets, which constitute>95% of the total adipocyte volume, are composed mainly of triglycerides. Triglycerides are step-wise broken down to diglycerides, monoglycerides and glycerol and FAs (Figure 1). This process is usually complete, meaning that one molecule of glycerol and three molecules of FAs are produced by the hydrolysis of one molecule of triglyceride. However, the release of FAs and glycerol from fat cells does not occur in the ratio of 3:1 because some FAs are re-utilized by

Regulation of lipolysis

The lipolytic process is under intense regulation and there is a marked diurnal variability in circulating levels of FAs and glycerol, reflecting hormonal and other regulatory events.1, 8, 9, 10, 11, 12 The most important regulatory factors are summarized in Table 1. In rodents, a number of hormones have a strong influence on lipolysis. In humans, only catecholamines, natriuretic peptides and insulin have pronounced acute effects. In humans, growth hormone has some long-term permissive effects

Pathophysiological states

A number of pathophysiological conditions are associated with alterations in the regulation of adipocyte lipolysis. The most important are obesity, metabolic (insulin resistance) syndrome, familial combined hyperlipidaemia and polycystic ovarian syndrome (PCOS). However, detailed information is only available for obesity and PCOS, and these conditions will be discussed in more detail below.

Conclusions

Fat cell lipolysis is subject to intense regulation by hormones, cytokines, physiological factors and pathophysiological factors. Furthermore, genetic variation is of importance. Major species differences in the regulation of fat cell lipolysis exist, making it difficult to draw clinical conclusions from animal experiments. A number of conditions that are associated with insulin resistance, such as obesity, metabolic syndrome, PCOS and familial combined hyperlipidaemia, also display alterations

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