Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice

Apolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and brown adipose tissue. In this study the focus wa...

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Main Authors: Patricia Recio-López, Ismael Valladolid-Acebes, Per-Olof Berggren, Lisa Juntti-Berggren
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/1/62
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author Patricia Recio-López
Ismael Valladolid-Acebes
Per-Olof Berggren
Lisa Juntti-Berggren
author_facet Patricia Recio-López
Ismael Valladolid-Acebes
Per-Olof Berggren
Lisa Juntti-Berggren
author_sort Patricia Recio-López
collection DOAJ
description Apolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and brown adipose tissue. In this study the focus was on subcutaneous (SAT) and visceral (VAT) white adipose tissue (WAT). Mice were either given HFD for 14 weeks and directly from start also treated with antisense oligonucleotide (ASO) against apoCIII or given HFD for 10 weeks and HFD+ASO for an additional 14 weeks. Both groups had animals treated with inactive (Scr) ASO as controls and in parallel chow-fed mice were injected with saline. Preventing an increase or lowering apoCIII in the HFD-fed mice decreased adipocytes’ size, reduced expression of inflammatory cytokines and increased expression of genes related to thermogenesis and beiging. Isolated adipocytes from both VAT and SAT from the ASO-treated mice had normal insulin-induced inhibition of lipolysis compared to cells from Scr-treated mice. In conclusion, the HFD-induced metabolic derangements in WATs can be prevented and reversed by lowering apoCIII.
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spelling doaj.art-5acae07117464b26884578b699d878fa2023-11-23T11:34:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-012316210.3390/ijms23010062Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in MicePatricia Recio-López0Ismael Valladolid-Acebes1Per-Olof Berggren2Lisa Juntti-Berggren3The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, SwedenThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, SwedenThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, SwedenThe Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, SwedenApolipoprotein CIII (apoCIII) is proinflammatory and increases in high-fat diet (HFD)-induced obesity and insulin resistance. We have previously shown that reducing apoCIII improves insulin sensitivity in vivo by complex mechanisms involving liver and brown adipose tissue. In this study the focus was on subcutaneous (SAT) and visceral (VAT) white adipose tissue (WAT). Mice were either given HFD for 14 weeks and directly from start also treated with antisense oligonucleotide (ASO) against apoCIII or given HFD for 10 weeks and HFD+ASO for an additional 14 weeks. Both groups had animals treated with inactive (Scr) ASO as controls and in parallel chow-fed mice were injected with saline. Preventing an increase or lowering apoCIII in the HFD-fed mice decreased adipocytes’ size, reduced expression of inflammatory cytokines and increased expression of genes related to thermogenesis and beiging. Isolated adipocytes from both VAT and SAT from the ASO-treated mice had normal insulin-induced inhibition of lipolysis compared to cells from Scr-treated mice. In conclusion, the HFD-induced metabolic derangements in WATs can be prevented and reversed by lowering apoCIII.https://www.mdpi.com/1422-0067/23/1/62apolipoprotein CIIIdiet-induced obesityinsulin resistancewhite adipose tissueinflammationantisense oligonucleotides
spellingShingle Patricia Recio-López
Ismael Valladolid-Acebes
Per-Olof Berggren
Lisa Juntti-Berggren
Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice
International Journal of Molecular Sciences
apolipoprotein CIII
diet-induced obesity
insulin resistance
white adipose tissue
inflammation
antisense oligonucleotides
title Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice
title_full Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice
title_fullStr Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice
title_full_unstemmed Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice
title_short Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice
title_sort apolipoprotein ciii reduction protects white adipose tissues against obesity induced inflammation and insulin resistance in mice
topic apolipoprotein CIII
diet-induced obesity
insulin resistance
white adipose tissue
inflammation
antisense oligonucleotides
url https://www.mdpi.com/1422-0067/23/1/62
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AT ismaelvalladolidacebes apolipoproteinciiireductionprotectswhiteadiposetissuesagainstobesityinducedinflammationandinsulinresistanceinmice
AT perolofberggren apolipoproteinciiireductionprotectswhiteadiposetissuesagainstobesityinducedinflammationandinsulinresistanceinmice
AT lisajunttiberggren apolipoproteinciiireductionprotectswhiteadiposetissuesagainstobesityinducedinflammationandinsulinresistanceinmice