Pre-Weaning Exposure to Maternal High-Fat Diet Is a Critical Developmental Window for Programming the Metabolic System of Offspring in Mice

Hong Yang; Nan Chen; Lei Fan; Xiaojing Lin; Juncheng Liu; Yuehua You; Ying Zhong; Yan Chen; Jibin Li; Xiaoqiu Xiao

doi:10.3389/fendo.2022.816107

Pre-Weaning Exposure to Maternal High-Fat Diet Is a Critical Developmental Window for Programming the Metabolic System of Offspring in Mice

Front Endocrinol (Lausanne). 2022 Feb 10:13:816107. doi: 10.3389/fendo.2022.816107. eCollection 2022.

Authors

Hong Yang^{1

2}, Nan Chen^{1

2}, Lei Fan^{2

3}, Xiaojing Lin^{1

2}, Juncheng Liu^{1

2}, Yuehua You^{1

2}, Ying Zhong^{2

4}, Yan Chen^{2

5}, Jibin Li⁴, Xiaoqiu Xiao^{1

2

3}

Affiliations

¹ Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
³ Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China.
⁴ Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing, China.
⁵ Department of Endocrinology and Nephrology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.

Abstract

Background: Maternal high-fat diet (HFD) during pregnancy and lactation exerts long-term effects on the health of offspring. However, the critical developmental window for metabolic programming of maternal exposure to HFD on pathogenesis of obesity in offspring needs further clarification.

Materials & methods: Female ICR mice were fed low-fat diet (LFD) or HFD for 8 weeks until delivery. During lactation, half of LFD dams received HFD while the other half of LFD dams and HFD dams maintained the previous diet. Male offspring were weaned at postnatal day 21 (P21) and fed LFD or HFD for 7 weeks. Metabolic parameters, biochemical, and histological indicators of thermogenesis, rectal temperature, and sympathetic nerve tone were detected at P21 and 10 weeks old.

Results: At P21, LH (maternal LFD before delivery but HFD during lactation) and HH (maternal HFD before delivery and during lactation) offspring gained more body weight and showed higher serum glucose and triglyceride levels as compared with LL (maternal LFD before delivery and during lactation), and the metabolic characters were maintained until 10 weeks age when fed with LFD after weaning. However, LH offspring exhibited a greater degree of metabolic abnormalities compared to HH offspring, with increased body weight, as well as lower norepinephrine (NE)-stimulated rectal temperature rise when fed with HFD after weaning. The lower UCP1 levels and HSL phosphorylation in LH offspring further suggested that brown adipose tissue (BAT) thermogenic function was impaired.

Conclusion: Exposure to maternal HFD feeding during pre-weaning period alone showed similar detrimental effects on programming metabolic system of offspring as those of both prenatal and early postnatal HFD feeding. Early postnatal stage is a critical time window for metabolic programming and has profound and long-lasting effects on BAT development and function through sympathetic nerve-mediated thermogenesis.

Keywords: gestation; high-fat diet (HFD); lactation; offspring; thermogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue, Brown / metabolism*
Animals
Body Temperature
Diet, High-Fat*
Female
Lactation
Maternal Nutritional Physiological Phenomena
Metabolic Diseases / etiology*
Mice
Mice, Inbred ICR
Obesity / etiology
Pregnancy
Prenatal Exposure Delayed Effects
Sympathetic Nervous System / physiology
Thermogenesis*
Weaning*
Weight Gain