Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue

Wieneke Dijk, Frits Mattijssen, Montserrat de la Rosa Rodriguez, Angel Loza Valdes, Anne Loft, Susanne Mandrup, Eric Kalkhoven, Ling Qi, Jan Willem Borst, Sander Kersten

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Triglycerides are stored in specialized organelles called lipid droplets. Numerous proteins have been shown to be physically associated with lipid droplets and govern their function. Previously, the protein hypoxia-inducible lipid droplet-associated (HILPDA) was localized to lipid droplets and was suggested to inhibit triglyceride lipolysis in hepatocytes. We confirm the partial localization of HILPDA to lipid droplets and show that HILPDA is highly abundant in adipose tissue, where its expression is controlled by the peroxisome proliferator-activated receptor γ and by β-adrenergic stimulation. Levels of HILPDA markedly increased during 3T3-L1 adipocyte differentiation. Nevertheless, silencing of Hilpda using small interfering RNA or overexpression of Hilpda using adenovirus did not show a clear impact on 3T3-L1 adipogenesis. Following β-adrenergic stimulation, the silencing of Hilpda in adipocytes did not significantly alter the release of nonesterified fatty acids (NEFA) and glycerol. By contrast, adenoviral-mediated overexpression of Hilpda modestly attenuated the release of NEFA from adipocytes following β-adrenergic stimulation. In mice, adipocyte-specific inactivation of Hilpda had no effect on plasma levels of NEFA and glycerol after fasting, cold exposure, or pharmacological β-adrenergic stimulation. In addition, other relevant metabolic parameters were unchanged by adipocyte-specific inactivation of Hilpda. Taken together, we find that HILPDA is highly abundant in adipose tissue, where its levels are induced by peroxisome proliferator-activated receptor γ and β-adrenergic stimulation. In contrast to the reported inhibition of lipolysis by HILPDA in hepatocytes, our data do not support an important direct role of HILPDA in the regulation of lipolysis in adipocytes in vivo and in vitro.

OriginalsprogEngelsk
TidsskriftEndocrinology
Vol/bind158
Udgave nummer5
Sider (fra-til)1231-1251
ISSN0013-7227
DOI
StatusUdgivet - 2017

Fingeraftryk

Adipose Tissue
Adipocytes
Adrenergic Agents
Nonesterified Fatty Acids
Hepatocytes
Lipid Droplets
Adipogenesis
Adenoviridae
Small Interfering RNA
Fasting
Proteins

Citer dette

Dijk, Wieneke ; Mattijssen, Frits ; de la Rosa Rodriguez, Montserrat ; Loza Valdes, Angel ; Loft, Anne ; Mandrup, Susanne ; Kalkhoven, Eric ; Qi, Ling ; Borst, Jan Willem ; Kersten, Sander. / Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue. I: Endocrinology. 2017 ; Bind 158, Nr. 5. s. 1231-1251.
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title = "Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue",
abstract = "Triglycerides are stored in specialized organelles called lipid droplets. Numerous proteins have been shown to be physically associated with lipid droplets and govern their function. Previously, the protein hypoxia-inducible lipid droplet-associated (HILPDA) was localized to lipid droplets and was suggested to inhibit triglyceride lipolysis in hepatocytes. We confirm the partial localization of HILPDA to lipid droplets and show that HILPDA is highly abundant in adipose tissue, where its expression is controlled by the peroxisome proliferator-activated receptor γ and by β-adrenergic stimulation. Levels of HILPDA markedly increased during 3T3-L1 adipocyte differentiation. Nevertheless, silencing of Hilpda using small interfering RNA or overexpression of Hilpda using adenovirus did not show a clear impact on 3T3-L1 adipogenesis. Following β-adrenergic stimulation, the silencing of Hilpda in adipocytes did not significantly alter the release of nonesterified fatty acids (NEFA) and glycerol. By contrast, adenoviral-mediated overexpression of Hilpda modestly attenuated the release of NEFA from adipocytes following β-adrenergic stimulation. In mice, adipocyte-specific inactivation of Hilpda had no effect on plasma levels of NEFA and glycerol after fasting, cold exposure, or pharmacological β-adrenergic stimulation. In addition, other relevant metabolic parameters were unchanged by adipocyte-specific inactivation of Hilpda. Taken together, we find that HILPDA is highly abundant in adipose tissue, where its levels are induced by peroxisome proliferator-activated receptor γ and β-adrenergic stimulation. In contrast to the reported inhibition of lipolysis by HILPDA in hepatocytes, our data do not support an important direct role of HILPDA in the regulation of lipolysis in adipocytes in vivo and in vitro.",
keywords = "3T3-L1 Cells, Adipocytes, Adipogenesis, Adipose Tissue, Animals, Female, Lipid Droplets, Lipolysis, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasm Proteins, Journal Article",
author = "Wieneke Dijk and Frits Mattijssen and {de la Rosa Rodriguez}, Montserrat and {Loza Valdes}, Angel and Anne Loft and Susanne Mandrup and Eric Kalkhoven and Ling Qi and Borst, {Jan Willem} and Sander Kersten",
note = "Copyright {\circledC} 2017 Endocrine Society.",
year = "2017",
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language = "English",
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journal = "Endocrinology",
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Dijk, W, Mattijssen, F, de la Rosa Rodriguez, M, Loza Valdes, A, Loft, A, Mandrup, S, Kalkhoven, E, Qi, L, Borst, JW & Kersten, S 2017, 'Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue', Endocrinology, bind 158, nr. 5, s. 1231-1251. https://doi.org/10.1210/en.2016-1809

Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue. / Dijk, Wieneke; Mattijssen, Frits; de la Rosa Rodriguez, Montserrat; Loza Valdes, Angel; Loft, Anne; Mandrup, Susanne; Kalkhoven, Eric; Qi, Ling; Borst, Jan Willem; Kersten, Sander.

I: Endocrinology, Bind 158, Nr. 5, 2017, s. 1231-1251.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue

AU - Dijk, Wieneke

AU - Mattijssen, Frits

AU - de la Rosa Rodriguez, Montserrat

AU - Loza Valdes, Angel

AU - Loft, Anne

AU - Mandrup, Susanne

AU - Kalkhoven, Eric

AU - Qi, Ling

AU - Borst, Jan Willem

AU - Kersten, Sander

N1 - Copyright © 2017 Endocrine Society.

PY - 2017

Y1 - 2017

N2 - Triglycerides are stored in specialized organelles called lipid droplets. Numerous proteins have been shown to be physically associated with lipid droplets and govern their function. Previously, the protein hypoxia-inducible lipid droplet-associated (HILPDA) was localized to lipid droplets and was suggested to inhibit triglyceride lipolysis in hepatocytes. We confirm the partial localization of HILPDA to lipid droplets and show that HILPDA is highly abundant in adipose tissue, where its expression is controlled by the peroxisome proliferator-activated receptor γ and by β-adrenergic stimulation. Levels of HILPDA markedly increased during 3T3-L1 adipocyte differentiation. Nevertheless, silencing of Hilpda using small interfering RNA or overexpression of Hilpda using adenovirus did not show a clear impact on 3T3-L1 adipogenesis. Following β-adrenergic stimulation, the silencing of Hilpda in adipocytes did not significantly alter the release of nonesterified fatty acids (NEFA) and glycerol. By contrast, adenoviral-mediated overexpression of Hilpda modestly attenuated the release of NEFA from adipocytes following β-adrenergic stimulation. In mice, adipocyte-specific inactivation of Hilpda had no effect on plasma levels of NEFA and glycerol after fasting, cold exposure, or pharmacological β-adrenergic stimulation. In addition, other relevant metabolic parameters were unchanged by adipocyte-specific inactivation of Hilpda. Taken together, we find that HILPDA is highly abundant in adipose tissue, where its levels are induced by peroxisome proliferator-activated receptor γ and β-adrenergic stimulation. In contrast to the reported inhibition of lipolysis by HILPDA in hepatocytes, our data do not support an important direct role of HILPDA in the regulation of lipolysis in adipocytes in vivo and in vitro.

AB - Triglycerides are stored in specialized organelles called lipid droplets. Numerous proteins have been shown to be physically associated with lipid droplets and govern their function. Previously, the protein hypoxia-inducible lipid droplet-associated (HILPDA) was localized to lipid droplets and was suggested to inhibit triglyceride lipolysis in hepatocytes. We confirm the partial localization of HILPDA to lipid droplets and show that HILPDA is highly abundant in adipose tissue, where its expression is controlled by the peroxisome proliferator-activated receptor γ and by β-adrenergic stimulation. Levels of HILPDA markedly increased during 3T3-L1 adipocyte differentiation. Nevertheless, silencing of Hilpda using small interfering RNA or overexpression of Hilpda using adenovirus did not show a clear impact on 3T3-L1 adipogenesis. Following β-adrenergic stimulation, the silencing of Hilpda in adipocytes did not significantly alter the release of nonesterified fatty acids (NEFA) and glycerol. By contrast, adenoviral-mediated overexpression of Hilpda modestly attenuated the release of NEFA from adipocytes following β-adrenergic stimulation. In mice, adipocyte-specific inactivation of Hilpda had no effect on plasma levels of NEFA and glycerol after fasting, cold exposure, or pharmacological β-adrenergic stimulation. In addition, other relevant metabolic parameters were unchanged by adipocyte-specific inactivation of Hilpda. Taken together, we find that HILPDA is highly abundant in adipose tissue, where its levels are induced by peroxisome proliferator-activated receptor γ and β-adrenergic stimulation. In contrast to the reported inhibition of lipolysis by HILPDA in hepatocytes, our data do not support an important direct role of HILPDA in the regulation of lipolysis in adipocytes in vivo and in vitro.

KW - 3T3-L1 Cells

KW - Adipocytes

KW - Adipogenesis

KW - Adipose Tissue

KW - Animals

KW - Female

KW - Lipid Droplets

KW - Lipolysis

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Neoplasm Proteins

KW - Journal Article

U2 - 10.1210/en.2016-1809

DO - 10.1210/en.2016-1809

M3 - Journal article

VL - 158

SP - 1231

EP - 1251

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 5

ER -