Additive Effects of Omega-3 Fatty Acids and Thiazolidinediones in Mice Fed a High-Fat Diet: Triacylglycerol/Fatty Acid Cycling in Adipose Tissue

Overview

Journal Nutrients

Date 2020 Dec 9

PMID 33291653

Citations 9

Authors

Kristina Bardova

Jiri Funda

Radek Pohl

Tomas cajka

Michal Hensler

Ondrej Kuda

Petra Janovska

Katerina Adamcova

Ilaria Irodenko

Lucie Lenkova

Petr Zouhar

Olga Horakova

Pavel Flachs

Martin Rossmeisl

Jerry Colca

Jan Kopecky

Affiliations

Soon will be listed here.

Abstract

Long-chain n-3 polyunsaturated fatty acids (Omega-3) and anti-diabetic drugs thiazolidinediones (TZDs) exhibit additive effects in counteraction of dietary obesity and associated metabolic dysfunctions in mice. The underlying mechanisms need to be clarified. Here, we aimed to learn whether the futile cycle based on the hydrolysis of triacylglycerol and re-esterification of fatty acids (TAG/FA cycling) in white adipose tissue (WAT) could be involved. We compared Omega-3 (30 mg/g diet) and two different TZDs-pioglitazone (50 mg/g diet) and a second-generation TZD, MSDC-0602K (330 mg/g diet)-regarding their effects in C57BL/6N mice fed an obesogenic high-fat (HF) diet for 8 weeks. The diet was supplemented or not by the tested compound alone or with the two TZDs combined individually with Omega-3. Activity of TAG/FA cycle in WAT was suppressed by the obesogenic HF diet. Additive effects in partial rescue of TAG/FA cycling in WAT were observed with both combined interventions, with a stronger effect of Omega-3 and MSDC-0602K. Our results (i) supported the role of TAG/FA cycling in WAT in the beneficial additive effects of Omega-3 and TZDs on metabolism of diet-induced obese mice, and (ii) showed differential modulation of WAT gene expression and metabolism by the two TZDs, depending also on Omega-3.

Citing Articles

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Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity.

Benova A, Ferencakova M, Bardova K, Funda J, Prochazka J, Spoutil F Commun Biol. 2023; 6(1):1043.

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Delta-6 desaturase (Fads2) deficiency alters triacylglycerol/fatty acid cycling in murine white adipose tissue.

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Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat.

Oeckl J, Janovska P, Adamcova K, Bardova K, Brunner S, Dieckmann S Mol Metab. 2022; 61:101499.

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Adipose tissue-specific ablation of PGC-1β impairs thermogenesis in brown fat.

Funda J, Villena J, Bardova K, Adamcova K, Irodenko I, Flachs P Dis Model Mech. 2022; 15(4).

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References

McCommis K, Hodges W, Brunt E, Nalbantoglu I, McDonald W, Holley C . Targeting the mitochondrial pyruvate carrier attenuates fibrosis in a mouse model of nonalcoholic steatohepatitis. Hepatology. 2016; 65(5):1543-1556. PMC: 5397348. DOI: 10.1002/hep.29025. View

Fukunaga T, Zou W, Rohatgi N, Colca J, Teitelbaum S . An insulin-sensitizing thiazolidinedione, which minimally activates PPARγ, does not cause bone loss. J Bone Miner Res. 2014; 30(3):481-8. PMC: 4472363. DOI: 10.1002/jbmr.2364. View

Bederman I, Foy S, Chandramouli V, Alexander J, Previs S . Triglyceride synthesis in epididymal adipose tissue: contribution of glucose and non-glucose carbon sources. J Biol Chem. 2008; 284(10):6101-8. PMC: 2649080. DOI: 10.1074/jbc.M808668200. View

Kuda O, Stankova B, Tvrzicka E, Hensler M, Jelenik T, Rossmeisl M . Prominent role of liver in elevated plasma palmitoleate levels in response to rosiglitazone in mice fed high-fat diet. J Physiol Pharmacol. 2010; 60(4):135-40. View

Colca J, Tanis S, McDonald W, Kletzien R . Insulin sensitizers in 2013: new insights for the development of novel therapeutic agents to treat metabolic diseases. Expert Opin Investig Drugs. 2013; 23(1):1-7. DOI: 10.1517/13543784.2013.839659. View

Sanderson L, de Groot P, Hooiveld G, Koppen A, Kalkhoven E, Muller M . Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics. PLoS One. 2008; 3(2):e1681. PMC: 2244803. DOI: 10.1371/journal.pone.0001681. View

Adamcova K, Horakova O, Bardova K, Janovska P, Brezinova M, Kuda O . Reduced Number of Adipose Lineage and Endothelial Cells in Epididymal fat in Response to Omega-3 PUFA in Mice Fed High-Fat Diet. Mar Drugs. 2018; 16(12). PMC: 6316446. DOI: 10.3390/md16120515. View

Tordjman J, Chauvet G, Quette J, Beale E, Forest C, Antoine B . Thiazolidinediones block fatty acid release by inducing glyceroneogenesis in fat cells. J Biol Chem. 2003; 278(21):18785-90. DOI: 10.1074/jbc.M206999200. View

Hui S, Cowan A, Zeng X, Yang L, TeSlaa T, Li X . Quantitative Fluxomics of Circulating Metabolites. Cell Metab. 2020; 32(4):676-688.e4. PMC: 7544659. DOI: 10.1016/j.cmet.2020.07.013. View

10.

Flachs P, Ruhl R, Hensler M, Janovska P, Zouhar P, Kus V . Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids. Diabetologia. 2011; 54(10):2626-38. DOI: 10.1007/s00125-011-2233-2. View

11.

Kuda O, Brezinova M, Rombaldova M, Slavikova B, Posta M, Beier P . Docosahexaenoic Acid-Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties. Diabetes. 2016; 65(9):2580-90. DOI: 10.2337/db16-0385. View

12.

Rossmeisl M, Medrikova D, van Schothorst E, Pavlisova J, Kuda O, Hensler M . Omega-3 phospholipids from fish suppress hepatic steatosis by integrated inhibition of biosynthetic pathways in dietary obese mice. Biochim Biophys Acta. 2013; 1841(2):267-78. DOI: 10.1016/j.bbalip.2013.11.010. View

13.

Teran-Garcia M, Adamson A, Yu G, Rufo C, Suchankova G, Dreesen T . Polyunsaturated fatty acid suppression of fatty acid synthase (FASN): evidence for dietary modulation of NF-Y binding to the Fasn promoter by SREBP-1c. Biochem J. 2007; 402(3):591-600. PMC: 1863568. DOI: 10.1042/BJ20061722. View

14.

Flachs P, Adamcova K, Zouhar P, Marques C, Janovska P, Viegas I . Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype. Int J Obes (Lond). 2016; 41(3):372-380. DOI: 10.1038/ijo.2016.228. View

15.

Veleba J, Kopecky Jr J, Janovska P, Kuda O, Horakova O, Malinska H . Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism. Nutr Metab (Lond). 2015; 12:52. PMC: 4667423. DOI: 10.1186/s12986-015-0047-9. View

16.

Harrison S, Alkhouri N, Davison B, Sanyal A, Edwards C, Colca J . Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled phase IIb study. J Hepatol. 2019; 72(4):613-626. DOI: 10.1016/j.jhep.2019.10.023. View

17.

Ruzickova J, Rossmeisl M, Prazak T, Flachs P, Sponarova J, Veck M . Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue. Lipids. 2005; 39(12):1177-85. DOI: 10.1007/s11745-004-1345-9. View

18.

Janovska P, Flachs P, Kazdova L, Kopecky J . Anti-obesity effect of n-3 polyunsaturated fatty acids in mice fed high-fat diet is independent of cold-induced thermogenesis. Physiol Res. 2012; 62(2):153-61. DOI: 10.33549/physiolres.932464. View

19.

Seiler S, Koves T, Gooding J, Wong K, Stevens R, Ilkayeva O . Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise. Cell Metab. 2015; 22(1):65-76. PMC: 4754082. DOI: 10.1016/j.cmet.2015.06.003. View

20.

Manson J, Cook N, Lee I, Christen W, Bassuk S, Mora S . Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2018; 380(1):23-32. PMC: 6392053. DOI: 10.1056/NEJMoa1811403. View