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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Published in:	International journal of molecular sciences 2022-01, Vol.23 (1), p.62
Main Authors:	Recio-López, Patricia, Valladolid-Acebes, Ismael, Berggren, Per-Olof, Juntti-Berggren, Lisa
Format:	Article
Language:	eng
Subjects:	Adipocytes Adipocytes - metabolism Adipose tissue Adipose tissue (brown) Adipose Tissue, Brown - metabolism Adipose Tissue, White - metabolism Animals Antisense oligonucleotides Apolipoprotein C-III Apolipoprotein C-III - metabolism apolipoprotein CIII Apolipoproteins Body fat Cytokines Diabetes Diet Diet, High-Fat diet-induced obesity Endokrinologi och diabetes Fysiologi Gene expression Genes High fat diet Inflammation Inflammation - metabolism Insulin Insulin - metabolism Insulin resistance Insulin Resistance - physiology Klinisk medicin Lipids Lipolysis Lipolysis - physiology Lipoproteins Liver - metabolism Male Medicin och hälsovetenskap Medicinska och farmaceutiska grundvetenskaper Metabolism Mice Mice, Inbred C57BL Obesity Obesity - metabolism Overweight Proteins Thermogenesis Thermogenesis - physiology Triglycerides Tumor necrosis factor-TNF white adipose tissue
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Summary:	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.
ISSN:	1422-0067 1661-6596 1422-0067