@article{e432b14c7575499186ba731e7b055dd2,
title = "Antioxidant effects of n-acetylcysteine prevent programmed metabolic disease in mice",
abstract = "An adverse maternal in utero and lactation environment can program offspring for increased risk for metabolic disease. The aim of this study was to determine whether N-acetylcysteine (NAC), an anti-inflammatory antioxidant, attenuates programmed susceptibility to obesity and insulin resistance in offspring of mothers on a high-fat diet (HFD) during pregnancy. CD1 female mice were acutely fed a standard breeding chow or HFD. NAC was added to the drinking water (1 g/kg) of the treatment cohorts from embryonic day 0.5 until the end of lactation. NAC treatment normalized HFD-induced maternal weight gain and oxidative stress, improved the maternal lipidome, and prevented maternal leptin resistance. These favor-able changes in the in utero environment normalized postnatal growth, decreased white adipose tissue (WAT) and hepatic fat, improved glucose and insulin tolerance and antioxidant capacity, reduced leptin and insulin, and increased adiponectin in HFD offspring. The lifelong metabolic improvements in the offspring were accompanied by reductions in proinflammatory gene expression in liver and WAT and increased thermogenic gene expression in brown adipose tissue. These results, for the first time, provide a mechanistic rationale for how NAC can prevent the onset of metabolic disease in the offspring of mothers who consume a typical Western HFD.",
author = "Charron, {Maureen J.} and Lyda Williams and Yoshinori Seki and Du, {Xiu Quan} and Bhagirath Chaurasia and Alan Saghatelian and Summers, {Scott A.} and Katz, {Ellen B.} and Vuguin, {Patricia M.} and Reznik, {Sandra E.}",
note = "Funding Information: Acknowledgments. The authors are very grateful to Dr. Ryan Pekson, Albert Einstein College of Medicine, for his valuable assistance with the preparation of some of the figures. This article is dedicated to the authors{\textquoteright} beloved co-author, colleague, and friend, Dr. Ellen B. Katz, who bravely worked on this manuscript in spite of her illness until the end. The authors regret that she was not able to see this work published. Funding. This work was supported by National Institutes of Health (NIH) grant R21 DK081194 (to M.J.C.), American Diabetes Association grant 1-13-CE-06 (to M.J.C.), and an NIH Ruth Kirschstein predoctoral fellowship (F31 DK093332 [to L.W.]). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. M.J.C. conceived the idea of the project, supervised all of the experiments, revised the figures, edited the manuscript, and provided funding. L.W. performed the experiments and produced the first draft of the manuscript. Y.S., X.Q.D., B.C., A.S., S.A.S., and E.B.K. provided intellectual input into the design of the project and assisted with some experiments. P.M.V. provided intellectual input into the design of the project and edited the manuscript. S.E.R. evaluated the data, interpreted the histopathology, and revised the manuscript. M.J.C. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2020 by the American Diabetes Association.",
year = "2020",
month = aug,
doi = "10.2337/db19-1129",
language = "English (US)",
volume = "69",
pages = "1650--1661",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "8",
}
