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.
Bibliographical noteFunding Information:
Funding: This work was supported by the Swedish Diabetes Association, Funds of Karolinska Institutet, The Sigurd and Elsa Goljes Foundation, The Swedish Research Council, Novo Nordisk Foundation, The Family Erling-Persson Foundation, Strategic Research Program in Diabetes at Karolinska Institutet, The Family Knut and Alice Wallenberg Foundation, The Stichting af Jochnick Foundation, Skandia Insurance Company Ltd., Diabetes and Wellness Foundation, The Bert von Kantzow Foundation, Svenska Diabetesstiftelsen, AstraZeneca, Swedish Association for Diabetology and The ERC-EYLETS 834860.
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Diet-induced obesity
- White adipose tissue
- Antisense oligonucleotides
- Insulin resistance
- Apolipoprotein CIII
- Mice, Inbred C57BL
- Adipose Tissue, White/metabolism
- Apolipoprotein C-III/metabolism
- Diet, High-Fat
- Adipose Tissue, Brown/metabolism
- Insulin Resistance/physiology