Inclusion of microbe-derived antioxidant during pregnancy and lactation attenuates high-fat diet-induced hepatic oxidative stress, lipid disorders, and NLRP3 inflammasome in mother rats and offspring

  • Zhen Luo
  • Xue Xu
  • Sen Zhao
  • Takami Sho
  • Wenli Luo
  • Jing Zhang
  • Weina Xu
  • Kong Hon
  • Jianxiong Xu
Keywords: high fat diet; Liver; microbiota-fermented antioxidants; NLRP3 inflammasome; rats


Objective: This study aimed to evaluate the effects of microbe-derived antioxidant (MA) on high-fat diet (HFD)-induced hepatic lipid disorders in mother rats and offspring.

Methods: A total of 36 female rats were randomly divided into three groups at the beginning of pregnancy: the control group (CG), HFD, and HFD with 2% MA. Mother rats were slaughtered at the first and 10th day of lactation (L1 and L10) and offspring were slaughtered at L10. The plasma and liver of mother rats, and liver of offspring were collected.

Results: The results showed that MA reversed HFD-induced activities of inducible nitric oxide synthase (iNOS) and antioxidative enzymes in liver of mother rats and offspring. In addition, MA reduced HFD-induced lipid accumulation through decreasing the low-density lipoprotein cholesterol (LDLC) content in plasma of mother rats and improving hepatic fatty acid synthase (FAS) in mother rats and offspring. MA decreased HFD-induced hepatic alkaline phosphatase (AKP) activity in liver of mother rats and offspring. Furthermore, MA reduced HFD-activated nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in liver of mother rats and offspring.

Conclusions: MA supplementation reversed HFD-induced hepatic oxidative stress, lipid accumulation, NLRP3 inflammasome, and function in mother rats and offspring, suggesting MA can be functional ingredients to improve maternal-fetal health.


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Author Biographies

Zhen Luo

school of agriculture and biology

Xue Xu

school of agriculture and biology

Sen Zhao

school of agriculture and biology

Takami Sho

school of agriculture and biology

Wenli Luo

school of agriculture and biology

Jing Zhang

school of agriculture and biology

Weina Xu

school of agriculture and biology


  1. Cannon MV, Buchner DA, Hester J, Miller H, Sehayek E, Nadeau JH, et al. Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring. PLoS One 2014; 9: e90335. doi: 10.1371/journal.pone.0090335.

  2. Heerwagen MJ, Miller MR, Barbour LA, Friedman JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol 2010; 299: R711. doi: 10.1152/ajpregu.00310.2010.

  3. Gregorio BM, Souza-Mello V, Carvalho JJ, Mandarim-De-Lacerda CA, Aguila MB. Maternal high-fat intake predisposes nonalcoholic fatty liver disease in C57BL/6 offspring. Am J Obstet Gynecol 2010; 203: 495.e491–8. doi: 10.1016/j.ajog.2010.06.042.

  4. Ashino NG, Saito KN, Souza FD, Nakutz FS, Roman EA, Velloso LA, et al. Maternal high-fat feeding through pregnancy and lactation predisposes mouse offspring to molecular insulin resistance and fatty liver. J Nutrl Biochem 2012; 23: 341–8. doi: 10.1016/j.jnutbio.2010.12.011.

  5. Benatti RO, Melo AM, Borges FO, Ignacio-Souza LM, Simino LA, Milanski M, et al. Maternal high-fat diet consumption modulates hepatic lipid metabolism and microRNA-122 (miR-122) and microRNA-370 (miR-370) expression in offspring. Br J Nutr 2014; 111: 2112–22. doi: 10.1017/S0007114514000579.

  6. Zhu MJ, Kang Y, Xue Y, Liang X, García M, Rodgers D, et al. Red raspberries suppress NLRP3 inflammasome and attenuate metabolic abnormalities in diet-induced obese mice. J Nutr Biochem 2017; 53: 96. doi: 10.1016/j.jnutbio.2017.10.012.

  7. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 2011; 17: 179–88. doi: 10.1038/nm.2279.

  8. Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, et al. Fatty acid-induced NLRP3-PYCARD inflammasome activation interferes with insulin signaling. Nat Immunol 2011; 12: 408. doi: 10.1038/ni.2022.

  9. Li J, Cordero P, Solanki A, Vinciguerra M, Crompton T, Oben JA. Maternal obesity programs offspring’s liver immune cells intra-uterine. J Hepatol 2018; 68: S353–4. doi: 10.1016/S0168-8278(18)30930-9.

  10. Li S, Tan H-Y, Wang N, Zhang Z-J, Lao L, Wong C-W, et al. The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci 2015; 16: 26087–124. doi: 10.3390/ijms161125942.

  11. Blasa M, Angelino D, Gennari L, Ninfali P. The cellular antioxidant activity in red blood cells (CAA-RBC): a new approach to bioavailability and synergy of phytochemicals and botanical extracts. Food Chem 2011; 125: 685–91. doi: 10.1016/j.foodchem.2010.09.065.

  12. Xu J, Xu C, Chen X, Cai X, Yang S, Sheng Y, et al. Regulation of an antioxidant blend on intestinal redox status and major microbiota in early weaned piglets. Nutrition 2014; 30: 584–9. doi: 10.1016/j.nut.2013.10.018.

  13. Cai X, Chen X-L, Yang F, Xu J-X, Gu J, Zhang C. A preliminary research of antioxidant capacity by micro-derived antioxidants in vitro. Biotechnology 2011; 21: 84–7. doi: 10.3969/j.issn.1004-311X.2011.06.160

  14. Zhao S, Li S, Xu X, Zhong Q, Zhang J, Xu W, et al. Effects of micro-derived antioxidants on antioxidant capacity and litter size in high fat diet-induced pregnant rats. J. Sichuan Agricult Univ 2017; 35: 594–8. doi:10.16036/j.issn.1000-2650.2017.04.021

  15. Carmiel-Haggai M, Cederbaum AI, Nieto N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J 2005; 19: 136–8. doi: 10.1096/fj.04-2291fje.

  16. Dowman JK, Tomlinson JW, Newsome PN. Pathogenesis of non-alcoholic fatty liver disease. QJM Mon J Assoc Phys 2010; 103: 71. doi: 10.1093/qjmed/hcp158.

  17. Klop B, Elte JW, Cabezas MC. Dyslipidemia in obesity: mechanisms and potential targets. Nutrients 2013; 5: 1218–40. doi: 10.3390/nu5041218.

  18. Yamaguchi R, Nakagawa Y, Liu YJ, Fujisawa Y, Sai S, Nagata E, et al. Effects of maternal high-fat diet on serum lipid concentration and expression of peroxisomal proliferator-activated receptors in the early life of rat offspring. Horm Metab Res 2010; 42: 821–5. doi: 10.1055/s-0030-1261954.

  19. Zhang X-L, Wu Y-F, Wang Y-S, Wang X-Z, Piao C-H, Liu J-M, et al. The protective effects of probiotic-fermented soymilk on high-fat diet-induced hyperlipidemia and liver injury. J Funct Foods 2017; 30: 220–7. doi: 10.1016/j.jff.2017.01.002.

  20. Nido SA, Shituleni SA, Mengistu BM, Liu Y, Khan AZ, Gan F, et al. Effects of selenium-enriched probiotics on lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in mice fed a high-fat diet. Biol Trace Elem Res 2016; 171: 399–409. doi: 10.1007/s12011-015-0552-8.

  21. Choi S-B, Lew L-C, Yeo S-K, Nair Parvathy S, Liong M-T. Probiotics and the BSH-related cholesterol lowering mechanism: a Jekyll and Hyde scenario. Crit Rev Biotechnol 2015; 35: 392–401. doi: 10.3109/07388551.2014.889077.

  22. Jeun J, Kim S, Cho S-Y, Jun H-J, Park H-J, Seo J-G, et al. Hypocholesterolemic effects of Lactobacillus plantarum KCTC3928 by increased bile acid excretion in C57BL/6 mice. Nutrition 2010; 26: 321–30. doi: 10.1016/j.nut.2009.04.011.

  23. Bogdan C. Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol 2015; 36: 161–78. doi: 10.1016/

  24. Miyata T, Eckardt K, Nangaku M. Studies on renal disorders, oxidative stress in applied basic research and clinical practice, 2010. doi: 10.1007/978-1-60761-857-7.

  25. Schönfeld P, Wojtczak L. Fatty acids as modulators of the cellular production of reactive oxygen species. Free Radical Biol Med 2008; 45: 231–41.doi: 10.1016/j.freeradbiomed.2008.04.029.

  26. Chen P, Gu Y, Yu S, Xu J. Protective effects of microbe-derived antioxidant on lipopolysaccharide-induced liver injury in rats. J. Shanghai Jiao Tong Univ (Agri Sci), 2016; 34: 17–22. doi: 10.3969/J.ISSN.1671-9964.2016.05.003

  27. Chen H, Jiang Y, Yang Z, Hu W, Xiong L, Wang N, et al. Effects of Chimonanthus nitens Oliv. Leaf extract on glycolipid metabolism and antioxidant capacity in diabetic model mice. Oxid Med Cell Longev 2017; 2017: 7648505. doi: 10.1155/2017/7648505.

  28. Ros P, Díaz F, Freire-Regatillo A, Argente-Arizón P, Barrios V, Argente J, et al. Resveratrol intake during pregnancy and lactation modulates the early metabolic effects of maternal nutrition differently in male and female offspring. Endocrinology 2017; 159: 810–25. doi: 10.1210/en.2017-00610.

  29. Mittal M, Chatterjee S, Flora SJS. Combination therapy with vitamin C and DMSA for arsenic–fluoride co-exposure in rats. Metallomics 2018; 10: 1291–306. doi: 10.1039/c8mt00192h.

  30. Luo Z, Zhu W, Guo Q, Luo W, Zhang J, Xu W, et al. Weaning induced hepatic oxidative stress, apoptosis, and aminotransferases through MAPK signaling pathways in piglets. Oxid Med Cell Longev 2016; 2016: 4768541. doi: 10.1155/2016/4768541.

  31. Riedl SJ, Shi Y. Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 2004; 5: 897. doi: 10.1038/nrm1496.

  32. Hyder MA, Hasan M, Mohieldein AH. Comparative levels of ALT, AST, ALP and GGT in liver associated diseases. Eur J Exp Biol 2013; 3: 280–4. ISSN: 2248-9215CODEN (USA):EJEBAU

  33. Kim J, Kim J, Kwon YH. Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice. Nutr Res Pract 2016; 10: 386–92. doi: 10.4162/nrp.2017.11.5.435.

  34. McCurdy CE, Bishop JM, Williams SM, Grayson BE, Smith MS, Friedman JE, et al. Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest 2009; 119: 323–35. doi: 10.1172/JCI32661.

  35. Lv Z, Fan H, Zhang B, Ning C, Xing K, Guo Y. Dietary genistein supplementation in laying broiler breeder hens alters the development and metabolism of offspring embryos as revealed by hepatic transcriptome analysis. FASEB J 2018; 32: 4214–28. doi: 10.1096/fj.201701457R.

  36. Boden G. Interaction between free fatty acids and glucose metabolism. Curr Opin Nutr Metab Care 2002; 5: 545–9. doi: 10.1097/00075197-200209000-00014

  37. Legrand-Poels S, Esser N, L’homme L, Scheen A, Paquot N, Piette J. Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes. Biochem Pharmacol 2014; 92: 131–41. doi: 10.1016/j.bcp.2014.08.013.

  38. Porras D, Nistal E, Martínez-Flórez S, Pisonero-Vaquero S, Olcoz JL, Jover R, et al. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation. Free Radical Biol Med 2017; 102: 188–202. doi: 10.1016/j.freeradbiomed.2016.11.037.

  39. Segovia SA, Vickers MH, Zhang XD, Gray C, Reynolds CM. Maternal supplementation with conjugated linoleic acid in the setting of diet-induced obesity normalises the inflammatory phenotype in mothers and reverses metabolic dysfunction and impaired insulin sensitivity in offspring. J Nutr Biochem 2015; 26: 1448–57. doi: 10.1016/j.jnutbio.2015.07.013.

  40. Wang YL, Han QQ, Gong WQ, Pan DH, Wang LZ, Hu W, et al. Microglial activation mediates chronic mild stress-induced depressive- and anxiety-like behavior in adult rats. J Neuroinflamm 2018; 15: 21.doi: 10.1186/s12974-018-1054-3.

  41. Long F, Wang N, Zhang R, Qiu H, Lv J, Wang X, et al. Effects of transplantation of bone marrow mesenchymal stem cells on hepatic injury and metabolism in rats with acute liver failure. Int J Clin Exp Med 2017; 10: 4881–8. doi: 1940-5901/IJCEM0045622

  42. Zhu JL, Chen Y, Liu J. Effects of nonylphenol on prostate cell apoptosis and expressions of caspase-3,caspase-8,and caspase-9 mRNA in male Wistar rats. Chinese J Pub Health 2013; 29: 1187–9. doi: 10.11847/zgggws2013-29-08-29

  43. Ashok I, Wankhar D, Wankhar W, Sheeladevi R. Neurobehavioral changes and activation of neurodegenerative apoptosis on long-term consumption of aspartame in the rat brain. J Nutr Intermed Metab 2015; 2: 76–85. doi: 10.1016/j.jnim.2015.09.001.

  44. Huang Y, Ye T, Liu C, Fang F, Chen Y, Dong Y. Maternal high-fat diet during pregnancy and lactation affects hepatic lipid metabolism in early life of offspring rat. J Biosciences 2017; 42: 311–19. doi: 10.1007/s12038-017-9675-8.

  45. Tang B, Zhang JG, Tan HY, Wei XQ. Astragaloside IV inhibits ventricular remodeling and improves fatty acid utilization in rats with chronic heart failure. Bioscience Rep 2018; 38: BSR20171036. doi: 10.1042/BSR20171036.

  46. Ning J, Sun Q, Qian S, Dang S, Chen G. Taurine promotes cognitive function in prenatally stressed juvenile ratsviaactivating the Akt-CREB-PGC1α pathway. Redox Biol 2016; 10: 179–90. doi: 10.1016/j.redox.2016.10.004.

How to Cite
Luo Z., Xu X., Zhao S., Sho T., Luo W., Zhang J., Xu W., Hon K., & Xu J. (2019). Inclusion of microbe-derived antioxidant during pregnancy and lactation attenuates high-fat diet-induced hepatic oxidative stress, lipid disorders, and NLRP3 inflammasome in mother rats and offspring. Food & Nutrition Research, 63.
Original Articles