Another hormone-sensitive triglyceride lipase in fat cells?

Saltiel, Alan R.

doi:10.1073/pnas.97.2.535

Cited by 21 publications

(19 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, BAY was less potent (70 versus 32 nM) and less efficacious (30 versus 90%) in reducing basal lipolysis than forskolin-stimulated lipolysis. These results are consistent with basal lipolysis still being present in adipocytes from HSL knockout mice (Osuga et al, 2000;Saltiel, 2000;Okazaki et al, 2002), and with basal lipolysis being carried out by an enzyme distinct from HSL. Together, our results support the suggestion that another lipase with similar functionality is present in adipose tissue (Osuga et al, 2000;Saltiel, 2000;Okazaki et al, 2002).…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

Specific Inhibition of Hormone-Sensitive Lipase Improves Lipid Profile while Reducing Plasma Glucose

Claus¹,

Lowe²,

Liang³

et al. 2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Elevation of plasma free fatty acids has been linked with insulin resistance and diabetes. Inhibition of lipolysis may provide a mechanism to decrease plasma fatty acids, thereby improving insulin sensitivity. Hormone-sensitive lipase (HSL) is a critical enzyme involved in the hormonally regulated release of fatty acids and glycerol from adipocyte lipid stores, and its inhibition may thus improve insulin sensitivity and blood glucose handling in type 2 diabetes. In rat adipocytes, forskolin-activated lipolysis was blocked by in vitro addition of a potent and selective HSL inhibitor or by prior treatment of the animals themselves. Antilipolytic effects also were demonstrated in overnight-fasted mice, rats, and dogs with species-dependent effects on plasma free fatty acid levels but with similar reductions in plasma glycerol being observed in all species. Inhibition of HSL also reduced hyperglycemia in streptozotocin-induced diabetic rats. The data support a connection between adipose tissue lipolysis and plasma glucose levels.

show abstract

Section: Discussionsupporting

confidence: 80%

“…Results with HSL knockout mice, however, have raised the question of whether it is a suitable target. Conflicting effects on both insulin sensitivity (Osuga et al, 2000;Saltiel, 2000;Wang et al, 2001;Haemmerle et al, 2002;Okazaki et al, 2002;Voshol et al, 2003) and insulin secretion (Roduit et al, 2001;Mulder et al, 2003) have been reported.…”

mentioning

confidence: 99%

Specific Inhibition of Hormone-Sensitive Lipase Improves Lipid Profile while Reducing Plasma Glucose

Claus¹,

Lowe²,

Liang³

et al. 2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…The animals' body weight and cold tolerance were unchanged, suggesting that HSL-independent lipolytic pathway(s) likely exist in fat cells (9). Similar phenotypic features, including sterility in male animals, were recently reported in an independently derived HSL-deficient mouse strain (10,11).…”

supporting

confidence: 50%

A Role for Hormone-Sensitive Lipase in Glucose-Stimulated Insulin Secretion

et al. 2001

View full text Add to dashboard Cite

Endogenous lipid stores are thought to be involved in the mechanism whereby the ␤-cell adapts its secretory capacity in obesity and diabetes. In addition, hormonesensitive lipase (HSL) is expressed in ␤-cells and may provide fatty acids necessary for the generation of coupling factors linking glucose metabolism to insulin release. We have recently created HSL-deficient mice that were used to directly assess the role of HSL in insulin secretion and action. HSL ؊/؊ mice were normoglycemic and normoinsulinemic under basal conditions, but showed an ϳ30% reduction of circulating free fatty acids (FFAs) with respect to control and heterozygous animals after an overnight fast. An intraperitoneal glucose tolerance test revealed that HSL-null mice were glucose-intolerant and displayed a lack of a rise in plasma insulin after a glucose challenge. Examination of plasma glucose during an insulin tolerance test suggested that HSL-null mice were insulin-resistant, because plasma glucose was barely lowered after the injection of insulin. Freshly isolated islets from HSL-deficient mice displayed elevated secretion at low (3 mmol/l) glucose, failed to release insulin in response to high (20 mmol/l) glucose, but had a normal secretion when challenged with elevated KCl. The phenotype of heterozygous mice with respect to the measured parameters in vitro was similar to that of wild type. Finally, the islet triglyceride content of HSL ؊/؊ mice was 2-2.5 fold that in HSL ؊/؉ and HSL ؉/؉ animals. The results demonstrate an important role of HSL and endogenous ␤-cell lipolysis in the coupling mechanism of glucose-stimulated insulin secretion. The data also provide direct support for the concept that some lipid molecule(s), such as FFAs, fatty acyl-CoA or their derivatives, are implicated in ␤-cell glucose signaling.

show abstract

“…Furthermore, at high insulin levels, there is also the possibility that insulin interacts with other receptors such as IGF-1. Finally, lipolytic response may also be regulated by another (as yet undefined) lipase, as has been suggested previously (30). Thus, the regulation of lipolysis by insulin or RSG may require more than changes in HSL expression to alter lipolytic activity (27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 85%

Insulin and Rosiglitazone Regulation of Lipolysis and Lipogenesis in Human Adipose Tissue In Vitro

et al. 2002

View full text Add to dashboard Cite

Lipolysis is an important process determining fuel metabolism, and insulin regulates this process in adipose tissue. The aim of this study was to investigate the long-term effects of insulin, an insulin enhancer (rosiglitazone [RSG]), and insulin in combination with RSG on the regulation of lipolysis and lipogenesis in human abdominal subcutaneous fat. Lipolysis and lipogenesis were assessed by protein expression studies of hormone-sensitive lipase (HSL) (84 kDa) and lipoprotein lipase (LPL) (56 kDa), respectively. In addition, lipolytic rate was assessed by glycerol release assay and tumor necrosis factor (TNF)-␣ release measured by enzyme-linked immunosorbent assay (n ‫؍‬ 12). In subcutaneous adipocytes, increasing insulin doses stimulated LPL expression, with maximal stimulation at 100 nmol/l insulin (control, 1.0 ؎ 0.0 [mean ؎ SE, protein expression relative to control]; 1 nmol/l insulin, 0.87 ؎ 0.13; 100 nmol/l insulin, 1.68 ؎ 0.19; P < 0.001). In contrast, insulin at the 100 nmol/l dose reduced the expression of HSL (100 nmol/l insulin, 0.49 ؎ 0.05; P < 0.05), while no significant reduction was observed at other doses. Higher doses of insulin stimulated both HSL (1,000 nmol/l insulin, 1.4 ؎ 0.07; P < 0.01) and LPL (control 1.00 ؎ 0.0; 1,000 nmol/l insulin, 2.66 ؎ 0.27; P < 0.01) protein expression. Cotreatment with RSG induced an increased dose response to insulin for LPL and HSL (P < 0.05); RSG alone also increased LPL and HSL expression (P < 0.05). Insulin stimulated TNF-␣ secretion in a dose-dependent manner (P < 0.01); the addition of RSG (10 ؊8 mol/l) reduced TNF-␣ secretion (P < 0.05). In summary, chronic treatment of human adipocytes with insulin stimulates lipolysis and LPL protein expression. The addition of RSG reduced the lipolytic rate and TNF-␣ secretion. The increase in lipolysis is not explained by changes in HSL expression. These data, therefore, may explain in part why hyperinsulinemia coexists with increased circulating nonesterified free fatty acids and increased adiposity in obese and/or type 2 diabetic patients.

show abstract

Another hormone-sensitive triglyceride lipase in fat cells?

Cited by 21 publications

References 16 publications

Specific Inhibition of Hormone-Sensitive Lipase Improves Lipid Profile while Reducing Plasma Glucose

Specific Inhibition of Hormone-Sensitive Lipase Improves Lipid Profile while Reducing Plasma Glucose

A Role for Hormone-Sensitive Lipase in Glucose-Stimulated Insulin Secretion

Insulin and Rosiglitazone Regulation of Lipolysis and Lipogenesis in Human Adipose Tissue In Vitro

Contact Info

Product

Resources

About