Coenzyme A and Its Thioester Pools in Obese Zucker and Zucker Diabetic Fatty Rats

Overview

Journal Nutrients

Date 2020 Feb 12

PMID 32041091

Citations 1

Authors

Shigeru Chohnan

Shiori Matsuno

Kei Shimizu

Yuka Tokutake

Daisuke Kohari

Atsushi Toyoda

Affiliations

Soon will be listed here.

Abstract

Feeding behavior is closely related to hypothalamic malonyl-CoA level in the brain and diet-induced obesity affects total CoA pools in liver. Herein, we performed a comprehensive analysis of the CoA pools formed in thirteen tissues of Zucker and Zucker diabetic fatty (ZDF) rats. Hypothalamic malonyl-CoA levels in obese rats remained low and were almost the same as those of lean rats, despite obese rats having much higher content of leptin, insulin, and glucose in their sera. Regardless of the -genotypes, larger total CoA pools were formed in the livers of ZDF rats and the size of hepatic total CoA pools in Zucker rats showed almost one tenth of the size of ZDF rats. The decreased total CoA pool sizes in Zucker rats was observed in the brown adipose tissues, while ZDF-fatty rats possessed 6% of total CoA pool in the lean rats in response to deficiency. This substantially lower CoA content in the obese rats would be disadvantageous to non-shivering thermogenesis. Thus, comparing the intracellular CoA behaviors between Zucker and ZDF rats, as well as the lean and fatty rats of each strain would help to elucidate features of obesity and type 2 diabetes in combination with result (s) of differential gene expression analysis and/or comparative genomics.

Citing Articles

Effects of Obesity and Diabesity on Ventricular Muscle Structure and Function in the Zucker Rat.

Sultan A, Adeghate E, Emerald B, Qureshi M, Minhas S, Howarth F Life (Basel). 2022; 12(8).

PMID: 36013400 PMC: 9410105. DOI: 10.3390/life12081221.

References

Reilly S, Tillander V, Ofman R, Alexson S, Hunt M . The nudix hydrolase 7 is an Acyl-CoA diphosphatase involved in regulating peroxisomal coenzyme A homeostasis. J Biochem. 2008; 144(5):655-63. DOI: 10.1093/jb/mvn114. View

Ramaswamy G, Karim M, Murti K, Jackowski S . PPARalpha controls the intracellular coenzyme A concentration via regulation of PANK1alpha gene expression. J Lipid Res. 2003; 45(1):17-31. DOI: 10.1194/jlr.M300279-JLR200. View

Yao J, Subramanian C, Rock C, Jackowski S . Human pantothenate kinase 4 is a pseudo-pantothenate kinase. Protein Sci. 2019; 28(6):1031-1047. PMC: 6511746. DOI: 10.1002/pro.3611. View

Gao S, Kinzig K, Aja S, Scott K, Keung W, Kelly S . Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake. Proc Natl Acad Sci U S A. 2007; 104(44):17358-63. PMC: 2077261. DOI: 10.1073/pnas.0708385104. View

Wilfred B, Wang W, Nelson P . Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways. Mol Genet Metab. 2007; 91(3):209-17. PMC: 1978064. DOI: 10.1016/j.ymgme.2007.03.011. View

Mizuno M, Sada T, Kato M, Koike H . Renoprotective effects of blockade of angiotensin II AT1 receptors in an animal model of type 2 diabetes. Hypertens Res. 2002; 25(2):271-8. DOI: 10.1291/hypres.25.271. View

Coimbra T, Janssen U, Grone H, Ostendorf T, Kunter U, Schmidt H . Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes. Kidney Int. 2000; 57(1):167-82. DOI: 10.1046/j.1523-1755.2000.00836.x. View

Leonardi R, Zhang Y, Rock C, Jackowski S . Coenzyme A: back in action. Prog Lipid Res. 2005; 44(2-3):125-53. DOI: 10.1016/j.plipres.2005.04.001. View

Jonas M, Edelman E, Groothuis A, Baker A, Seifert P, Rogers C . Vascular neointimal formation and signaling pathway activation in response to stent injury in insulin-resistant and diabetic animals. Circ Res. 2005; 97(7):725-33. DOI: 10.1161/01.RES.0000183730.52908.C6. View

10.

Peterson R, Little L, Neel M . WKY Fatty Rat as a Model of Obesity and Non-insulin-dependent Diabetes Mellitus. Ilar News. 2021; 32(3):13-15. PMC: 7793032. DOI: 10.1093/ilar.32.3.13. View

11.

Kong L, Wu H, Cui W, Zhou W, Luo P, Sun J . Advances in murine models of diabetic nephropathy. J Diabetes Res. 2013; 2013:797548. PMC: 3697778. DOI: 10.1155/2013/797548. View

12.

Takamura Y, Kitayama Y, Arakawa A, Yamanaka S, Tosaki M, Ogawa Y . Malonyl-CoA: acetyl-CoA cycling. A new micromethod for determination of acyl-CoAs with malonate decarboxylase. Biochim Biophys Acta. 1985; 834(1):1-7. DOI: 10.1016/0005-2760(85)90170-5. View

13.

Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L . miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 2002; 16(6):720-8. PMC: 155365. DOI: 10.1101/gad.974702. View

14.

Aleixandre de Artinano A, Miguel Castro M . Experimental rat models to study the metabolic syndrome. Br J Nutr. 2009; 102(9):1246-53. DOI: 10.1017/S0007114509990729. View

15.

Gowans G, Hawley S, Ross F, Grahame Hardie D . AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 2013; 18(4):556-66. PMC: 3791399. DOI: 10.1016/j.cmet.2013.08.019. View

16.

Hu Z, Cha S, Chohnan S, Lane M . Hypothalamic malonyl-CoA as a mediator of feeding behavior. Proc Natl Acad Sci U S A. 2003; 100(22):12624-9. PMC: 240668. DOI: 10.1073/pnas.1834402100. View

17.

Etgen G, Oldham B . Profiling of Zucker diabetic fatty rats in their progression to the overt diabetic state. Metabolism. 2000; 49(5):684-8. DOI: 10.1016/s0026-0495(00)80049-9. View

18.

Trajkovski M, Hausser J, Soutschek J, Bhat B, Akin A, Zavolan M . MicroRNAs 103 and 107 regulate insulin sensitivity. Nature. 2011; 474(7353):649-53. DOI: 10.1038/nature10112. View

19.

Clark J, Palmer C, Shaw W . The diabetic Zucker fatty rat. Proc Soc Exp Biol Med. 1983; 173(1):68-75. DOI: 10.3181/00379727-173-41611. View

20.

Himeno K, Seike M, Fukuchi S, Masaki T, Kakuma T, Sakata T . Heterozygosity for leptin receptor (fa) accelerates hepatic triglyceride accumulation without hyperphagia in Zucker rats. Obes Res Clin Pract. 2013; 3(1):1-52. DOI: 10.1016/j.orcp.2008.10.003. View