Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning

TY - JOUR

T1 - Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning

AU - Bartelt, Alexander

AU - John, Clara

AU - Cherradi, Mona Lisa

AU - Niemeier, Andreas

AU - Tödter, Klaus

AU - Heeren, Joerg

AU - Scheja, Ludger

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Efficient storage of dietary and endogenous fatty acids is a prerequisite for a healthy adipose tissue function. Lipoprotein lipase (LPL) is the master regulator of fatty acid uptake from triglyceride-rich lipoproteins. In addition to LPL-mediated fatty acid uptake, adipocytes are able to synthesize fatty acids from non-lipid precursor, a process called de novo lipogenesis (DNL). As the physiological relevance of fatty acid uptake versus DNL for brown and white adipocyte function remains unclear, we studied the role of adipocyte LPL using adipocyte-specific LPL knockout animals (aLKO). ALKO mice displayed a profound increase in DNL-fatty acids, especially palmitoleate and myristoleate in brown adipose tissue (BAT) and white adipose tissue (WAT) depots while essential dietary fatty acids were markedly decreased. Consequently, we found increased expression in adipose tissues of genes encoding DNL enzymes (Fasn, Scd1, and Elovl6) as well as the lipogenic transcription factor carbohydrate response element binding protein-β. In a high-fat diet (HFD) study aLKO mice were characterized by reduced adiposity and improved plasma insulin and adipokines. However, neither glucose tolerance nor inflammatory markers were ameliorated in aLKO mice compared to controls. No signs of increased BAT activation or WAT browning were detected in aLKO mice either on HFD or after 1 week of β3-adrenergic stimulation using CL316,243. We conclude that despite a profound increase in DNL-derived fatty acids, proposed to be metabolically favorable, aLKO mice are not protected from metabolic disease per se. In addition, induction of DNL alone is not sufficient to promote browning of WAT. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

AB - Efficient storage of dietary and endogenous fatty acids is a prerequisite for a healthy adipose tissue function. Lipoprotein lipase (LPL) is the master regulator of fatty acid uptake from triglyceride-rich lipoproteins. In addition to LPL-mediated fatty acid uptake, adipocytes are able to synthesize fatty acids from non-lipid precursor, a process called de novo lipogenesis (DNL). As the physiological relevance of fatty acid uptake versus DNL for brown and white adipocyte function remains unclear, we studied the role of adipocyte LPL using adipocyte-specific LPL knockout animals (aLKO). ALKO mice displayed a profound increase in DNL-fatty acids, especially palmitoleate and myristoleate in brown adipose tissue (BAT) and white adipose tissue (WAT) depots while essential dietary fatty acids were markedly decreased. Consequently, we found increased expression in adipose tissues of genes encoding DNL enzymes (Fasn, Scd1, and Elovl6) as well as the lipogenic transcription factor carbohydrate response element binding protein-β. In a high-fat diet (HFD) study aLKO mice were characterized by reduced adiposity and improved plasma insulin and adipokines. However, neither glucose tolerance nor inflammatory markers were ameliorated in aLKO mice compared to controls. No signs of increased BAT activation or WAT browning were detected in aLKO mice either on HFD or after 1 week of β3-adrenergic stimulation using CL316,243. We conclude that despite a profound increase in DNL-derived fatty acids, proposed to be metabolically favorable, aLKO mice are not protected from metabolic disease per se. In addition, induction of DNL alone is not sufficient to promote browning of WAT. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

KW - Adipocytes

KW - Adipogenesis

KW - Adipokines

KW - Adipose Tissue, Brown

KW - Adipose Tissue, White

KW - Adrenergic beta-3 Receptor Agonists

KW - Animals

KW - Diet, High-Fat

KW - Dioxoles

KW - Glucose Tolerance Test

KW - Hypertriglyceridemia

KW - Lipids

KW - Lipogenesis

KW - Lipoprotein Lipase

KW - Lipoproteins

KW - Mice

KW - Mice, Knockout

KW - RNA, Messenger

KW - Real-Time Polymerase Chain Reaction

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - Triglycerides

U2 - 10.1016/j.bbalip.2012.11.011

DO - 10.1016/j.bbalip.2012.11.011

M3 - SCORING: Journal article

C2 - 23228690

VL - 1831

SP - 934

EP - 942

JO - BBA-MOL CELL BIOL L

JF - BBA-MOL CELL BIOL L

SN - 1388-1981

IS - 5

ER -