Isolation and Characterization of the Gene for Mouse Hormone-Sensitive Lipase

Li, Zhigao; Sumida, Michihiro; Birchbauer, Andrea; Schotz, Michael C.; Reue, Karen

doi:10.1006/geno.1994.1614

Cited by 40 publications

(36 citation statements)

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“…11 kDa is consistent with this domain comprising the residues from 658 to the carboxyl-terminus of the HSL polypeptide and containing the hydrophobic sequence (FLSLAALC) (residues 735 742 of rat HSL), proposed to represent a possible lipid-binding site [4]. Recently, analysis of the mouse gene for HSL has shown the presence of an exon (exon 9) which may encode this putative lipid-binding domain [22].…”

Section: Lipid Binding Motifsupporting

confidence: 58%

Evidence for a multi‐domain structure for hormone‐sensitive lipase

Smith

Garton

Aitken³

et al. 1996

FEBS Letters

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Section: Lipid Binding Motifsupporting

confidence: 58%

Evidence for a multi‐domain structure for hormone‐sensitive lipase

Smith

Garton

Aitken³

et al. 1996

FEBS Letters

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“…Rat and mouse HSL adi share 94% identity at the protein level, whereas rat and human share 83% (12,13,21). The novel HSL region described here consists of 43 amino acids and the level of homology between rat and mouse is similar to that of the rest of the protein.…”

Section: Resultsmentioning

confidence: 80%

“…1C depicts the predicted amino acid sequence encoded by exon A in rat, mouse, and human. The peptides display strong positive charge and have a molecular mass of ϳ5 kDa, which well The genomic organization is very similar between mouse and human (13,21). The organization of the HSL gene in rat is not known, but is likely to be similar.…”

Section: Resultsmentioning

confidence: 93%

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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“…Also downregulated were Solute carrier family 27, which catalyzes the transfer of long-chain fatty acids across the plasma membrane (39), and CD36 antigen, which encodes a fatty acid translocase. Another group of genes showing a decrease in expression in the old heart is involved in lipolysis; this group includes Triacylglycerol hydrolase, which mobilizes triacylglycerol from storage pools (40), Lipase, hormone sensitive, which catalyzes the rate-limiting step in adipose tissue lipolysis (41), and Acyl-CoA thioesterase 1, cytosolic, which modulates the cellular levels of fatty acid-CoA ligands. Aging also down-regulated several genes involved in fatty acid ␤-oxidation in mitochondria (Table 1).…”

Section: Aging Results In Down-regulation Of Genes Involved In Fatty mentioning

confidence: 99%

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

Lee

Allison

Brand

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

289

218

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To provide a global analysis of gene expression in the aging heart, we monitored the expression of 9,977 genes simultaneously in 5-and 30-month-old male B6C3F1 mice by using high-density oligonucleotide microarrays and several statistical techniques. Aging was associated with transcriptional alterations consistent with a metabolic shift from fatty acid to carbohydrate metabolism, increased expression of extracellular matrix genes, and reduced protein synthesis. Caloric restriction (CR) started at 14 months of age resulted in a 19% global inhibition of age-related changes in gene expression. Interestingly, CR also resulted in alterations in gene expression consistent with preserved fatty acid metabolism, reduced endogenous DNA damage, decreased innate immune activity, apoptosis modulation, and a marked cytoskeletal reorganization. These observations provide evidence that aging of the heart is associated with specific transcriptional alterations, and that CR initiated in middle age may retard heart aging by inducing a profound transcriptional reprogramming.W hen started either early in life or at middle age, caloric restriction (CR) increases average and maximum lifespan, and reduces the incidence and delays the onset of spontaneous cancers and several other age-related diseases (1). Additionally, CR reduces the age-associated increase in reactive oxygen species (ROS)-induced molecular damage (2-5). Previously, we have used high-density oligonucleotide arrays to define aging and CR-related transcriptional alterations in mouse skeletal muscle (6) and brain (7). These reports provided evidence for an age-associated stress response characterized by the induction of heat-shock factors and other oxidative stress-induced transcripts. CR prevented these age-related alterations completely or partially. Both studies provided further support for the concept that oxidative stress may be an important, and perhaps underlying cause of the aging process of postmitotic tissues.The cardiac myocyte is the most energy demanding cell in the body, contracting constantly, 3 billion times or more in the average human lifespan (8), requiring large supplies of high-energy phosphates (9). Age-related changes in human and rodent hearts include a reduction in the number of myocytes (10, 11), myocyte hypertrophy (11, 12), cardiac fibrosis (13), lipofuscin pigment accumulation (14), a reduction in calcium transport across sarcoplasmic reticulum membrane (15), and alterations in the response to ␤-adrenergic stimulation (16). Collectively, these alterations likely contribute to age-related heart diseases being the leading cause of mortality in the U.S. (17). CR reduces the severity of spontaneous cardiomyopathy in male Sprague-Dawley rats (18) and prevents age-associated alterations in late diastolic function in B6D2F 1 mice (19). At the molecular level, CR reduces the concentration of both 8-hydroxydeoxyguanosine in DNA (20) and dityrosine cross-linking of proteins (21) in the heart of aging mice, and prevents somatic mitochondrial genomic rear...

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Isolation and Characterization of the Gene for Mouse Hormone-Sensitive Lipase

Cited by 40 publications

References 0 publications

Evidence for a multi‐domain structure for hormone‐sensitive lipase

Evidence for a multi‐domain structure for hormone‐sensitive lipase

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

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

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