Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol

Fredrikson, Gudrun; Törnqvist, Hans; Belfrage, Per

doi:10.1016/0005-2760(86)90286-9

Cited by 188 publications

(123 citation statements)

References 25 publications

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“…Although recognised as an important enzyme for the complete hydrolysis of triglycerides in WAT [28], the modulation of MGL has not received much attention. The finding that rosiglitazone increases MGL mRNA levels in congruence with WAT basal lipolysis indicates that this enzyme may also be one of its regulated steps, as well as one additional level of action of PPARγ agonism thereupon.…”

Section: Discussionmentioning

confidence: 99%

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

et al. 2006

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Aims/hypothesis The aim of this study was to investigate the effect and mechanisms of action of in vivo peroxisome proliferator-activated receptor γ (PPARγ) activation on white adipose tissue (WAT) lipolysis and NEFA metabolism. Materials and methods Study rats were treated for 7 days with 15 mg/kg of rosiglitazone per day; control rats were not treated. After a 6-h fast, lipolysis and levels of mRNA for lipases were assessed in explants from various adipose depots. Results Rosiglitazone markedly increased basal and noradrenaline (norepinephrine)-stimulated glycerol and NEFA release from WAT explants, and amplified their inhibition by insulin. Primary adipocytes isolated from PPARγ agonist-treated rats were also more responsive to noradrenaline stimulation expressed per cell, ruling out a contribution of an altered number of mature adipocytes in explants. Rosiglitazone concomitantly increased levels of mRNA transcripts for adipose triglyceride lipase (ATGL) and monoglyceride lipase (MGL) in subcutaneous and visceral WAT, and mRNA for hormone-sensitive lipase (HSL) in subcutaneous WAT. Lipase expression increased within 12 h of in vitro exposure of naïve explants to rosiglitazone, suggesting direct transcriptional activation. In parallel, chronic in vivo treatment with rosiglitazone lowered plasma NEFAs and exerted in WAT its expected stimulatory action on glycerol and NEFA recycling, and on the expression of genes involved in NEFA uptake and retention by WAT, such processes counteracting net NEFA export. Conclusions/interpretation These findings demonstrate that, in the face of its plasma NEFA-lowering action, PPARγ agonism stimulates WAT lipolysis, an effect that is compensated by lipid-retaining pathways. The results further suggest that PPARγ agonism stimulates lipolysis by increasing the lipolytic potential, including the expression levels of the genes encoding adipose triglyceride lipase and monoglyceride lipase.

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Section: Discussionmentioning

confidence: 99%

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

et al. 2006

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“…HSL ensures the hydrolysis of diglycerides, a step that is not under hormonal control, occurring at a much higher rate than the hydrolysis of triglycerides. Although HSL has the capacity to hydrolyse monoglycerides in vitro, monoglyceride lipase is required to obtain complete hydrolysis of monoglycerides in vivo [24]. Rodents show marked differences in the regulation of lipolysis at the receptor level, e.g.…”

Section: Discussionmentioning

confidence: 99%

Human adipose triglyceride lipase (PNPLA2) is not regulated by obesity and exhibits low in vitro triglyceride hydrolase activity

et al. 2006

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Aims/hypothesis: The recent identification of murine adipose triglyceride lipase (ATGL, now known as patatin-like phospholipase domain containing 2 [PNPLA2]), gene product of Pnpla2, has questioned the unique role of hormone sensitive lipase (HSL, now known as LIPE), gene product of Lipe, in fat cell lipolysis. Here, we investigated human ATGL and HSL adipose tissue gene expression and in vitro lipase activity. Subjects, materials and methods: Levels of mRNA in adipose tissue from healthy obese and non-obese subjects were measured and lipase activity and adipocyte lipolytic capacity determined. HSL and ATGL cDNAs were transfected into Cos-7 cells and the relative tri-and diglyceride hydrolase activities were measured. Results: Obesity was associated with a decreased subcutaneous and increased omental adipose tissue level of HSL mRNA. Subcutaneous HSL mRNA content was normalised upon weight reduction. In contrast, ATGL mRNA levels were unaffected by obesity and weight reduction. A high adipose tissue lipase activity was associated with increased maximal lipolysis and increased HSL, but not with ATGL mRNA levels. The in vitro triglyceride hydrolase activity of HSL was markedly higher than that of ATGL and contrary to HSL, ATGL was devoid of diglyceride hydrolase activity. The use of a selective HSL-inhibitor resulted in complete inhibition of HSL-mediated tri-and diglyceride hydrolase activity. The pH profile of human white adipose tissue triolein hydrolase activity was identical to that of HSL but differed from the ATGL profile. Conclusions/interpretation: HSL, but not ATGL gene expression shows a regulation according to obesity status and is associated with increased adipose tissue lipase activity. Moreover, HSL has a higher capacity than ATGL to hydrolyse triglycerides in vitro.

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“…Significant upregulation was also observed for the genes encoding the enzyme monoglyceride lipase (Mgll), which catalyzes the hydrolysis of monoglycerides to FA and glycerol. 40 Free FA generated by the action of the lipolytic enzymes are channeled toward b-oxidation (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

“…The combined action of Lpl and Pnliprp1 enzymes converts triglycerides to monoglycerides, which can be converted to free FAs and glycerol by the action of Mgl1. 40 The hydrolysis of triglycerides of chylomicrons and VLDL by the Lpl reduces plasma triglyceride levels and promotes the clearance of the resulting lipoprotein remnants by the LDL receptor, which recognizes and endocytoses ApoB-and ApoE-containing lipoproteins. 50,51 The monoglycerides that are produced by the action of Lpl and Pnliprp1 can be used for the synthesis of phospholipids that are incorporated into the HDL and other lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

et al. 2009

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We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and b-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.

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Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol

Cited by 188 publications

References 25 publications

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

PPARγ agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control

Human adipose triglyceride lipase (PNPLA2) is not regulated by obesity and exhibits low in vitro triglyceride hydrolase activity

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

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