Fructose Induces Insulin Resistance of Gestational Diabetes Mellitus in Mice via the NLRP3 Inflammasome Pathway

Yao Liu; Yuanhuan Wei; Lanlan Wu; Xiaoping Lin; Ruifang Sun; Hengying Chen; Siwen Shen; Guifang Deng

doi:10.3389/fnut.2022.839174

Fructose Induces Insulin Resistance of Gestational Diabetes Mellitus in Mice via the NLRP3 Inflammasome Pathway

Front Nutr. 2022 Apr 12:9:839174. doi: 10.3389/fnut.2022.839174. eCollection 2022.

Authors

Yao Liu¹, Yuanhuan Wei¹, Lanlan Wu¹, Xiaoping Lin², Ruifang Sun¹, Hengying Chen³, Siwen Shen¹, Guifang Deng¹

Affiliations

¹ Department of Clinical Nutrition, Union Shenzhen Hospital of Huazhong University of Science and Technology, Shenzhen, China.
² Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Nutrition and Food Hygiene, School of Public Health, Southern Medical University, Guangzhou, China.
³ Injury Prevention Research Center, Shantou University Medical College, Shantou, China.

Abstract

Background: Insulin resistance (IR), which is affected by dietary factors, is the main pathology underlying of gestational diabetes mellitus (GDM). Fructose (Fru), a sugar found in fruits, honey, and food sweeteners, has been reported to induce IR and inflammation. This study explored the effects and mechanisms of Fru on IR of GDM in pregnant and postpartum mice and their offspring.

Methods: The 6-week-old female C57BL/6J mice were randomly divided into control (Chow) and fructose (Fru) groups, with the latter receiving 20% (w/v) Fru in drinking water from 2 weeks before pregnancy to the end of pregnancy. The effects of Fru on IR and inflammation were determined using serum parameters, glucose metabolism tests, immunohistochemistry, and western blotting.

Results: Compared with the Chow group mice, pregnant mice treated with Fru exhibited greater gestational weight gain, higher fasting blood glucose and insulin concentrations, and a higher homeostasis model of assessment (HOMA) for IR index, but a lower HOMA for insulin sensitivity index. Treatment with Fru also increased the concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-17, and C-reactive protein in sera and the expression of IL-6, TNF-α, IL-17, and IL-1β mRNA in liver tissues of pregnant mice. Both CD68 and IL-1β positive cell were increased in Fru-treated mice compared with in Chow mice. Fru treatment also promoted IR and inflammation in mice at 4 weeks after delivery and in offspring mice. Mechanistically, Fru promoted the nuclear translocation of nuclear factor-kappa B (NF-κB) p65 to activate the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome.

Conclusions: Exposure to Fru before and during pregnancy induced IR in pregnant mice, which continued at 4 weeks postpartum and affected the offspring. The effects of Fru may be associated with activation of the NF-κB-NLRP3 pathway.

Keywords: fructose; gestational diabetes mellitus; insulin resistance; nuclear factor-κappa B; nucleotide-binding domain-like receptor protein 3 inflammasome.