Maternal high-fat diet-induced obesity in offspring: unraveling adipose tissue dysfunction mediated by increased heat shock proteins

Authors: PAZ, HENRY - University Arkansas For Medical Sciences (UAMS); BUDDHA, LASYA - University Arkansas For Medical Sciences (UAMS); LAM, TIANFU - University Arkansas For Medical Sciences (UAMS); ZHONG, YING - University Arkansas For Medical Sciences (UAMS); SIKES, JAMES - Arkansas Children'S Nutrition Research Center (ACNC); Shankar, Kartik; ANDRES, ALINE - University Arkansas For Medical Sciences (UAMS); WANKHADE, UMESH - University Arkansas For Medical Sciences (UAMS)

Submitted to: International Journal of Biochemistry and Cell Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2025
Publication Date: 6/13/2025
Citation: Paz, H.A., Buddha, L., Lam, T., Zhong, Y., Sikes, J.D., Shankar, K., Andres, A., Wankhade, U.D. 2025. Maternal high-fat diet-induced obesity in offspring: unraveling adipose tissue dysfunction mediated by increased heat shock proteins. International Journal of Biochemistry and Cell Biology. 186(2025). ARticle 106812. https://doi.org/10.1016/j.biocel.2025.106812.
DOI: https://doi.org/10.1016/j.biocel.2025.106812

Interpretive Summary: Maternal weight and diet before and during pregnancy play a significant role in shaping the long-term health of their children. Using a maternal diet-induced obesity mouse model, we show that male offspring born to high-fat diet-fed dams were more affected than those born to control diet-fed dams. They gained more weight, had higher body fat, showed poorer blood sugar control, and exhibited changes in blood markers. Their fat tissue also showed increased activity in genes linked to fat cell growth and proteins that help cells manage stress, called heat shock proteins (HSPs). Using cells, we discovered that these HSPs were more active during the development of white fat cells compared to brown fat cells, which are known for burning energy. These effects were sex-dependent, with male offspring being prominently affected. Interestingly, in human studies, we observed that a specific HSP (Hsp90AB1) was linked to a mother’s body mass index (BMI) in male but not female infants. This suggests that maternal weight may influence how these proteins function in males differently than in females. Our findings highlight how a mother’s diet and weight can impact her child’s health in complex, sex-specific ways.

Technical Abstract: Maternal weight and diet before and during pregnancy have a substantial impact on offspring metabolic health, though sex-specific differences in metabolic and adipose tissue adaptations to maternal overnutrition remain insufficiently understood. Using a mouse model of maternal high-fat (HF) diet-induced obesity, this study assessed the sexually dimorphic responses on offspring adiposity, physiology, and adipose tissue function. Male offspring of HF diet-fed dams showed more pronounced weight gain, altered body composition, impaired glucose homeostasis, changes in serum profile, and increased adipogenic and heat shock proteins (HSPs) gene expression in white adipose tissue compared to females. In cell culture, HSPs gene expression during differentiation was higher in white than in brown adipocytes. Also, expression of Hsp90AB1 in umbilical cord mesenchymal stem cells tended to positively correlate with maternal body mass index in male but not in female infants. Our findings, suggest a potential link between maternal diet, HSPs, and adipose tissue function.