Inactivation of lipoprotein lipase in 3T3-L1 adipocytes by angiopoietin-like protein 4 requires that both proteins have reached the cell surface

Makoveichuk, Elena; Vorrsjö, Evelina; Olivecrona, Thomas; Olivecrona, Gunilla

doi:10.1016/j.bbrc.2013.11.013

Cited by 21 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results show a 6-fold reduction in LPL after a 24 h-incubation in hypoxic conditions. Consistently, ANGPTL4, a major post-translational regulator of LPL activity which inactivates LPL at the plasma membrane of adipocytes [ 20 ], was significantly increased after hypoxia, as previously reported by Wood et al [ 21 ]. These observations confirm that the potential for lipid uptake of differentiated human preadipocytes is sensitive to an acute decrease in oxygen availability.…”

Section: Discussionsupporting

confidence: 83%

Effects of acute hypoxia on human adipose tissue lipoprotein lipase activity and lipolysis

et al. 2016

View full text Add to dashboard Cite

BackgroundAdipose tissue regulates postprandial lipid metabolism by storing dietary fat through lipoprotein lipase-mediated hydrolysis of exogenous triglycerides, and by inhibiting delivery of endogenous non-esterified fatty acid to nonadipose tissues. Animal studies show that acute hypoxia, a model of obstructive sleep apnea, reduces adipose tissue lipoprotein lipase activity and increases non-esterified fatty acid release, adversely affecting postprandial lipemia. These observations remain to be tested in humans.MethodsWe used differentiated human preadipocytes exposed to acute hypoxia as well as adipose tissue biopsies obtained from 10 healthy men exposed for 6 h to either normoxia or intermittent hypoxia following an isocaloric high-fat meal.ResultsIn differentiated preadipocytes, acute hypoxia induced a 6-fold reduction in lipoprotein lipase activity. In humans, the rise in postprandial triglyceride levels did not differ between normoxia and intermittent hypoxia. Non-esterified fatty acid levels were higher during intermittent hypoxia session. Intermittent hypoxia did not affect subcutaneous abdominal adipose tissue lipoprotein lipase activity. No differences were observed in lipolytic responses of isolated subcutaneous abdominal adipocytes between normoxia and intermittent hypoxia sessions.ConclusionsAcute hypoxia strongly inhibits lipoprotein lipase activity in differentiated human preadipocytes. Acute intermittent hypoxia increases circulating plasma non-esterified fatty acid in young healthy men, but does not seem to affect postprandial triglyceride levels, nor subcutaneous abdominal adipose tissue lipoprotein lipase activity and adipocyte lipolysis.

show abstract

Section: Discussionsupporting

confidence: 83%

Effects of acute hypoxia on human adipose tissue lipoprotein lipase activity and lipolysis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…However, both ANGPTL4 and LPL are secreted proteins that consequently are expected to be found at similar locations within the cell, which limits the applicability of immunofluorescence studies. Makoveichuk and coworkers found that ANGPTL4-producing cells have lower LPL activity in cell culture medium, but concluded that the inhibition of LPL by ANGPTL4 occurred after both proteins arrived at the cell surface (29,50). Our data suggest that ANGPTL4-mediated removal of LPL starts within cells, before LPL is secreted.…”

Section: Fig 6 Angptl4 Lowers Lpl Secretion A: Western Blot Of Medmentioning

confidence: 50%

“…At the same time, recent studies have raised the possibility that ANGPTL4 regulation of LPL might occur within the subendothelial spaces rather than along the capillary lumen (26)(27)(28). Studies of 3T3-L1 adipocytes suggested that inhibition of LPL activity by ANGPTL4 begins only after these proteins arrive at the cell surface (29). However, the extent to which the cultured cell studies are relevant to LPL activity in adipose tissue in vivo is uncertain.…”

Section: Wat Explantsmentioning

confidence: 99%

Angiopoietin-like 4 promotes intracellular degradation of lipoprotein lipase in adipocytes

Dijk

Beigneux

Larsson

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

LPL hydrolyzes triglycerides in triglyceride-rich lipoproteins along the capillaries of heart, skeletal muscle, and adipose tissue. The activity of LPL is repressed by angiopoietin-like 4 (ANGPTL4) but the underlying mechanisms have not been fully elucidated. Our objective was to study the cellular location and mechanism for LPL inhibition by ANGPTL4. We performed studies in transfected cells, ex vivo studies, and in vivo studies with Angptl4(-/-) mice. Cotransfection of CHO pgsA-745 cells with ANGPTL4 and LPL reduced intracellular LPL protein levels, suggesting that ANGPTL4 promotes LPL degradation. This conclusion was supported by studies of primary adipocytes and adipose tissue explants from wild-type and Angptl4(-/-) mice. Absence of ANGPTL4 resulted in accumulation of the mature-glycosylated form of LPL and increased secretion of LPL. Blocking endoplasmic reticulum (ER)-Golgi transport abolished differences in LPL abundance between wild-type and Angptl4(-/-) adipocytes, suggesting that ANGPTL4 acts upon LPL after LPL processing in the ER. Finally, physiological changes in adipose tissue ANGPTL4 expression during fasting and cold resulted in inverse changes in the amount of mature-glycosylated LPL in wild-type mice, but not Angptl4(-/-) mice. We conclude that ANGPTL4 promotes loss of intracellular LPL by stimulating LPL degradation after LPL processing in the ER.

show abstract

“…ANGPTL4 is involved in a variety of functions, including lipoprotein metabolism and angiogenesis (50, 51). Growing evidence indicates that ANGPTL4 serves as a potent inhibitor of the LPL enzyme, which hydrolyzes triglycerides from the apolipoprotein B – containing lipoproteins chylomicrons and VLDL (52).…”

Section: Angptl4mentioning

confidence: 99%

Angiopoietin-Like Proteins: A Comprehensive Look

2014

View full text Add to dashboard Cite

Angiopoietin-like proteins (ANGPTLs) are a family of proteins structurally similar to the angiopoietins. To date, eight ANGPTLs have been discovered, namely ANGPTL1 to ANGPTL8. Emerging evidence implies a key role for ANGPTLs in the regulation of a plethora of physiological and pathophysiological processes. Most of the ANGPTLs exhibit multibiological properties, including established functional roles in lipid and glucose metabolism, inflammation, hematopoiesis, and cancer. This report represents a systematic and updated appraisal of this class of proteins, focusing on the main features of each ANGPTL.

show abstract

Inactivation of lipoprotein lipase in 3T3-L1 adipocytes by angiopoietin-like protein 4 requires that both proteins have reached the cell surface

Cited by 21 publications

References 14 publications

Effects of acute hypoxia on human adipose tissue lipoprotein lipase activity and lipolysis

Effects of acute hypoxia on human adipose tissue lipoprotein lipase activity and lipolysis

Angiopoietin-like 4 promotes intracellular degradation of lipoprotein lipase in adipocytes

Angiopoietin-Like Proteins: A Comprehensive Look

Contact Info

Product

Resources

About