Immunological evidence for the presence of hormone-sensitive lipase in rat tissues other than adipose tissue

Holm, Cecilia; Belfrage, Per; Fredrikson, Gudrun

doi:10.1016/0006-291x(87)91081-3

Cited by 156 publications

(115 citation statements)

References 17 publications

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“…HSL remains a critical enzyme for complete TG lipolysis, and its characterization and function have been extensively reviewed elsewhere (35,78,83). HSL is expressed in adipocytes and less so in many other tissues, including skeletal muscle, pancreas, macrophages, and testis (34). HSL exerts lipolytic activity toward not only TG but also DG, MG, and cholesteryl esters.…”

Section: Regulation Of Tg Lipasesmentioning

confidence: 99%

Triacylglycerol lipases and metabolic control: implications for health and disease

Watt

Spriet

2010

American Journal of Physiology-Endocrinology and Metabolism

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Watt MJ, Spriet LL. Triacylglycerol lipases and metabolic control: implications for health and disease. Am J Physiol Endocrinol Metab 299: E162-E168, 2010. First published January 12, 2010; doi:10.1152/ajpendo.00698.2009.-Fatty acids derived from the hydrolysis of adipose tissue and skeletal muscle triacylglycerol (TG) are an important energy substrate at rest and during physical activity. This review outlines the identification of the new TG lipase, adipose triglyceride lipase, the current understanding of how cellular TG lipases are regulated, and the implications for understanding the integrated control of TG lipolysis. Furthermore, this review outlines recent advances that propose a "revised" role for TG lipases in cellular function, metabolic homeostasis, and disease prevention. fatty acid; metabolism; adipose; skeletal muscle TRIACYLGLYCEROLS (TG) are stored within discrete cytosolic lipid droplets within most tissues. Contrary to the common misconception in the literature that the TG pool is "inert," these droplets are highly dynamic, and the TG within is highly labile. The overall TG content within these droplets is ultimately dependent on the balance between the rates of TG hydrolysis and fatty acid uptake, oxidation, and storage. The fatty acids derived from TG breakdown participate in a variety of cellular processes, including membrane biosynthesis, signal transduction, and, most critically for this review, ATP production after ␤-oxidation. From a systemic viewpoint, fatty acids can be derived from both intracellular and extracellular sources, and with the exception of adipose tissue, the latter is most prevalent due to limited intracellular stores. Under postprandial conditions, ϳ30% of total energy expenditure is reliant on fatty acids derived from adipose TG hydrolysis, and this becomes quantitatively more important with extended fasting or exercise. In cases of caloric surplus leading to obesity, elevated circulating fatty acids may contribute to the accumulation of intramyocellular and hepatic lipids, which are associated with secondary metabolic complications such as insulin resistance (77). Therefore, the liberation of fatty acids from adipocyte TG and release into the systemic circulation is under most conditions the first point of control in the regulation of fatty acid metabolism, and accordingly, tight control of adipocyte lipolysis is a critical mediator of whole body metabolic homeostasis. Similarly, an emerging body of evidence indicates that altering TG metabolism within ectopic tissues, such as liver and skeletal muscle, can influence local fatty acid metabolism with implications for obesity-related metabolic disorders.This review will first focus on the regulation of TG lipolysis and how the understanding of TG regulation has evolved since the discovery and partial characterization of adipose triglyceride lipase (ATGL) only 5 years ago. The review will then outline how changes in TG metabolism can influence adipocyte and skeletal muscle metabolism and summarize the recent evidence sug...

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Section: Regulation Of Tg Lipasesmentioning

confidence: 99%

Triacylglycerol lipases and metabolic control: implications for health and disease

Watt

Spriet

2010

American Journal of Physiology-Endocrinology and Metabolism

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“…Antibodies used to demonstrate the binding of Sox5 and Sox6 to the chondrocyte-specific enhancer of the type II collagen gene (24) had no effect on the Sox-like protein binding to the HSL tes promoter. 3 To determine whether the AACAAAG sequence was important for in vivo testis expression of a reporter gene, a CAT construct containing the 0.5-kb region with a mutation of the site was used to produce different lines of transgenic mice. Five of the lines showed strong testis-specific CAT activity (Table I).…”

Section: Figmentioning

confidence: 99%

“…5) was not found with liver nuclear extracts and was not competed by an oligonucleotide containing a consensus site GGGGCG-GGG for Sp1. 3 Of note, an unidentified germ cell nuclear protein different from Sp1 binds to a GC box in the proximal promoter region of lactate dehydrogenase c that confers testisspecific expression (34). Mutation of the GT-rich binding region in transgenic mice abolished the testis-specific expression of the reporter gene, showing that, unlike the SRY/Sox consensus binding site, this region is required for the testis specificity of human HSL tes promoter activity.…”

Section: Figmentioning

confidence: 99%

“…In adipose tissue, HSL catalyzes the rate-limiting step in lipolysis, the catabolic pathway that mobilizes fatty acids from triacylglycerol stored in the lipid droplet. HSL is also expressed in rodent and human testis (3)(4)(5). In situ hybridization experiments performed in rat testis showed strong labeling of cells in the adluminal parts of the seminiferous tubules at stages X-XIV and sparsely distributed grains in the basal parts (6).…”

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Testis Hormone-sensitive Lipase Expression in Spermatids Is Governed by a Short Promoter in Transgenic Mice

Blaise¹,

Guillaudeux²,

Tavernier³

et al. 2001

Journal of Biological Chemistry

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A testicular form of hormone-sensitive lipase (HSL tes ), a triacylglycerol lipase, and cholesterol esterase, is expressed in male germ cells. Northern blot analysis showed HSL tes mRNA expression in early spermatids. Immunolocalization of the protein in human and rodent seminiferous tubules indicated that the highest level of expression occurred in elongated spermatids. We have previously shown that 0.5 kilobase pairs of the human HSL tes promoter directs testis-specific expression of a chloramphenicol acetyltransferase reporter gene in transgenic mice and determined regions binding nuclear proteins expressed in testis but not in liver (Blaise, R., Grober, J., Rouet, P., Tavernier, G., Daegelen, D., and Langin, D. (1999) J. Biol. Chem. 274, 9327-9334). Mutation of a SRY/Sox-binding site in one of the regions did not impair in vivo testis-specific expression of the reporter gene. Further transgenic analyses established that 95 base pairs upstream of the transcription start site were sufficient for correct testis expression. In gel retardation assays using early spermatid nuclear extracts, a germ cell-specific DNA-protein interaction was mapped between ؊46 and ؊29 base pairs. The DNA binding nuclear protein showed properties of zinc finger transcription factors. Mutation of the region abolished reporter gene activity in transgenic mice, showing that it is necessary for testis expression of HSL tes . Hormone-sensitive lipase (HSL)1 hydrolyzes triacylglycerol and, cholesterol and retinyl esters (1, 2). In adipose tissue, HSL catalyzes the rate-limiting step in lipolysis, the catabolic pathway that mobilizes fatty acids from triacylglycerol stored in the lipid droplet. HSL is also expressed in rodent and human testis (3-5). In situ hybridization experiments performed in rat testis showed strong labeling of cells in the adluminal parts of the seminiferous tubules at stages X-XIV and sparsely distributed grains in the basal parts (6). Immunohistochemistry experiments showed an HSL-like immunoreactivity in the adluminal part of the rat seminiferous tubules at stages XIII-VIII (5). The data suggested that rodent HSL mRNA and protein are expressed in haploid germ cells with a lag between mRNA and protein appearance. However, the precise germ cell type(s) expressing HSL was not determined in rat and it was not possible to rule out HSL expression in Sertoli cells. Moreover, the expression of HSL in germ cells of other mammalian species, including man, has not been documented. The effects of HSL gene disruption in mice have recently been reported (7). The most striking feature of the phenotype is male sterility due to oligospermia. Degenerated spermatocytes and spermatids were observed in HSL-deficient testis with a lack of mature spermatozoa. The data clearly demonstrate that HSL is required for spermatogenesis.The human adipose tissue form of HSL is encoded by 9 exons spanning 11 kb (8). The transcription start site was mapped in a short 5Ј-noncoding exon located 1.5 kb upstream of the first coding exon (9). The 2.8-kb mR...

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“…HSL has a broad substrate specificity, being able to hydrolyze, among others, mono-, di-, and triglycerides and cholesteryl esters. Besides ␤-cells and adipocytes, HSL is also present in testis, ovary, adrenal gland, heart, skeletal muscle (9), macrophages (10), and gastrointestinal tract mucosa (11). The HSL gene is located on chromosome 19 (human) (12) and spans 27 kb (Fig.…”

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A Novel Hormone-sensitive Lipase Isoform Expressed in Pancreatic β-Cells

Lindvall¹,

Nevsten²,

Ström³

et al. 2004

Journal of Biological Chemistry

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Hormone-sensitive lipase (HSL) is a key enzyme in fatty acid mobilization in many cell types. Two isoforms of HSL are known to date, namely HSL adi (84 kDa in rat) and HSL tes (130 kDa in rat). These are encoded by the same gene, with exons 1-9 encoding the parts that are common to both and an additional 5 -exon encoding the additional amino acids in HSL tes . HSL of various tissues, among these the islet of Langerhans, is larger than HSL adi , but not as large as HSL tes , indicating that there may be other 5 -coding exons. Here we describe the molecular basis for a novel 89-kDa HSL isoform that is expressed in ␤-cells, adipocytes, adrenal glands, and ovaries in the rat and that is encoded by exons 1-9 and exon A, which is spliced to exon 1 and thereby introducing an upstream start codon. The additional 5 -base pairs encode a 43-amino acid peptide, which is highly positively charged. Conglomerates of HSL molecules are in close association with the secretory granules of the ␤-cell, as determined by immunoelectron microscopy with antibodies targeting two separate regions of HSL. We have also determined that the human genomic sequence upstream of exon A has promoter activity in INS-1 cells as well as glucose sensing capability, mediating an increase in expression at high glucose concentration. The minimal promoter is present within 170 bp from the transcriptional start site and maximal glucose responsiveness is conferred by sequence within 850 bp from the transcriptional start site.Because of the established association between type 2 diabetes and obesity, lipids have received much attention in research on the pathophysiology of type 2 diabetes. Lipids are believed to cause insulin resistance in tissues and to alter ␤-cell function. The effect of lipids on ␤-cells has been studied extensively, but the picture that emerges is complex. Different effects are seen depending on parameters such as duration of exposure, concentration, and fatty acid chain length and saturation. Briefly, the presence of free fatty acids is essential for normal glucosestimulated insulin secretion (1, 2) and also has an amplifying action on glucose-stimulated insulin secretion. On the other hand, a prolonged exposure (24 -48 h) to high concentrations (ϳ1 mM) of free fatty acids is detrimental to ␤-cell function and survival (3, 4).In view of this, knowledge of lipid mobilization, lipid storage, and the regulation of these in the ␤-cell are of great interest. Recently, we showed that hormone-sensitive lipase (HSL) 1 is expressed and active in islets of Langerhans and clonal ␤-cells (5). HSL is a key enzyme in fatty acid mobilization in the adipocytes and presumably also in several non-adipocyte cell types (see Ref. 6 for review). It is unique among known lipases in that its activity is acutely controlled by hormones. Catabolic hormones, such as glucagon and catecholamines, activate the enzyme and anabolic hormones (e.g. insulin) decrease its activity. The activity of HSL is principally determined by the intracellular level of cAMP, which con...

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Immunological evidence for the presence of hormone-sensitive lipase in rat tissues other than adipose tissue

Cited by 156 publications

References 17 publications

Triacylglycerol lipases and metabolic control: implications for health and disease

Triacylglycerol lipases and metabolic control: implications for health and disease

Testis Hormone-sensitive Lipase Expression in Spermatids Is Governed by a Short Promoter in Transgenic Mice

A Novel Hormone-sensitive Lipase Isoform Expressed in Pancreatic β-Cells

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