Lipolysis: pathway under construction

  title={Lipolysis: pathway under construction},
  author={Rudolf Zechner and Juliane G. Strauss and Guenter Haemmerle and Achim Lass and Robert Zimmermann},
  journal={Current Opinion in Lipidology},
Purpose of review The lipolytic catabolism of stored fat in adipose tissue supplies tissues with fatty acids as metabolites and energy substrates during times of food deprivation. This review focuses on the function of recently discovered enzymes in adipose tissue lipolysis and fatty acid mobilization. Recent findings The characterization of hormone-sensitive lipase-deficient mice provided compelling evidence that hormone-sensitive lipase is not uniquely responsible for the hydrolysis of… 

The Regulation of Lipolysis in Adipose Tissue

Recent identification of the co-activator and inhibitor of ATGL have helped elucidate this important initial step of TAG breakdown, while also generating more questions.

The role of neutral lipases in human adipose tissue lipolysis

Two lipases the ‘old’ hormone sensitive lipase and the ’new’ adipose triglyceride lipase are of importance for the regulation of lipolysis in rodent fat cells, while adiposelycerine lipase seems essential for maintaining basal lipolytic activity, while hormonesensitive lipase is the enzyme most responsive to stimulated lipolytics.

Adipose Triglyceride Lipase and Hormone-sensitive Lipase Are the Major Enzymes in Adipose Tissue Triacylglycerol Catabolism*

Together, ATGL and HSL are responsible for more than 95% of the TG hydrolase activity present in murine WAT, suggesting that ATGL is the sole target for CGI-58-mediated activation of adipose lipolysis.

The Ins and Outs of Adipose Tissue

The aim of this chapter is to discuss what mechanisms are available to rapidly modulate fatty acid uptake/mobilization in adipose tissue. The major pathway for net uptake is lipoprotein lipase

Obese Yeast: Triglyceride Lipolysis Is Functionally Conserved from Mammals to Yeast*

Yeast Tgl4 is identified as a functional ortholog of mammalian adipose triglyceride lipase, and Serine 315 in the GXSXG lipase active site consensus sequence of the patatin domain of Tgl3 is essential for catalytic activity.

Lipid droplets in lipogenesis and lipolysis.

New data suggest that proteins previously implicated in vesicle trafficking, including Rabs, soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs), and motor and cytoskeletal proteins, likely orchestrate the movement and fusion of lipid droplets.

Dual Lipolytic Control of Body Fat Storage and Mobilization in Drosophila

Combined genetic, physiological, and biochemical analyses provide in vivo evidence that AKHR is as important for chronic accumulation and acute mobilization of storage fat as is the Brummer lipase, the homolog of mammalian adipose triglyceride lipase (ATGL).

Adipose Triglyceride Lipase (ATGL) and Hormone-Sensitive Lipase (HSL) Deficiencies Affect Expression of Lipolytic Activities in Mouse Adipose Tissues*

It is found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL- deficiency hardly showed any effect in brown fat tissue.

Minireview : Lipid Droplets in Lipogenesis and Lipolysis

New data suggest that proteins previously implicated in vesicle trafficking, including Rabs, soluble Nethylmaleimide sensitive factor attachment protein receptors (SNAREs), and motor and cytoskeletal proteins, likely orchestrate the movement and fusion of lipid droplets.



The Central Role of Perilipin A in Lipid Metabolism and Adipocyte Lipolysis

This review will focus on adipocyte lipolysis with emphasis on hormone signal transduction, lipolytic enzymes, the lipid storage droplet, and fatty acid release from the adipocyte.

Decreased fatty acid esterification compensates for the reduced lipolytic activity in hormone-sensitive lipase-deficient white adipose tissue Published, JLR Papers in Press, August 16, 2003. DOI 10.1194/jlr.M300190-JLR200

Results establish that in the absence of HSL, the reduced NEFA production is counteracted by a drastic reduction of NEFA reesterification that provides sufficient quantities ofNEFA for release into the circulation.

Lipolysis in the absence of hormone-sensitive lipase: evidence for a common mechanism regulating distinct lipases.

lipolysis is mediated not only by HSL but also by the non-HSL TG lipase, whose responses to lipolytic hormones are similar to those of HSL, and it is proposed that both lipases are regulated by common mechanism of lipolysis.

Molecular mechanisms regulating hormone-sensitive lipase and lipolysis.

  • C. Holm
  • Biology
    Biochemical Society transactions
  • 2003
Basal hyperinsulinaemia, release of exaggerated amounts of insulin during glucose challenges and retarded glucose disposal during insulin tolerance tests suggest that HSL-null mice are insulin resistant, suggesting the presence of additional, although not necessarily hormone-activatable, triacylglycerol lipase(s).

Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase

It is reported that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis, and it is interesting that ATGL contains a “patatin domain” common to plant acyl-hydrolases.

Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis.

Accumulating evidence has defined important functions for HSL in normal physiology, affecting adipocyte lipolysis, steroidogenesis, spermatogenesis, and perhaps insulin secretion and insulin action; however, direct links between abnormal expression or genetic variations of HSL and human disorders, such as obesity, insulin resistance, type 2 diabetes, and hyperlipidemia, await further clarification.

Carboxylesterase 3 (EC Is a Major Adipocyte Lipase*

Functional proteomics was used to detect non-HSL lipase(s) in mouse WAT and discovered two peaks of esterase activity using p-nitrophenyl butyrate as a substrate, which contained most of the lipase activity.

Hormone-sensitive Lipase Deficiency in Mice Causes Diglyceride Accumulation in Adipose Tissue, Muscle, and Testis*

In vivo results indicate that HSL is the rate-limiting enzyme for the cellular catabolism of DG in adipose tissue and muscle implying a substrate specificity of the enzyme in vivo.

Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation

It is shown that HSL is basally associated with lipid droplet surfaces at a low level in perilipin nulls, but that stimulated translocation from the cytosol to lipid droplets is absent in adipocytes derived from embryonic fibroblasts of perilip in-null mice.