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

Henry A Paz; Lasya Buddha; Tianfu Lam; Ying Zhong; James D Sikes; Kartik Shankar; Aline Andres; Umesh D Wankhade

doi:10.1016/j.biocel.2025.106812

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

Int J Biochem Cell Biol. 2025 Jun 11:186:106812. doi: 10.1016/j.biocel.2025.106812. Online ahead of print.

Authors

Henry A Paz¹, Lasya Buddha², Tianfu Lam², Ying Zhong³, James D Sikes², Kartik Shankar⁴, Aline Andres¹, Umesh D Wankhade⁵

Affiliations

¹ Arkansas Children's Nutrition Center, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
² Arkansas Children's Nutrition Center, Little Rock, AR, USA.
³ Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
⁴ USDA Agricultural Research Service, Responsive Agricultural Food Systems Research Unit, College Station, TX, USA.
⁵ Arkansas Children's Nutrition Center, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: udwankhade@uams.edu.

PMID: 40513769
DOI: 10.1016/j.biocel.2025.106812

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 exhibited greater weight gain and adiposity, impaired glucose homeostasis, elevated serum levels of insulin, leptin, and cholesterol, along with increased adipogenic and heat shock proteins (HSPs) gene expression in white adipose tissue compared to female offspring. In established adipocyte cell lines independent of experimental animals, the expression of HSPs during differentiation was higher in white than in brown adipocytes. Also, expression of Hsp90ab1 in human umbilical cord mesenchymal stem cells tended to positively correlate with maternal body mass index in male, but not in female infants. This finding was generated independently of the animal model and were intended to strengthen the translational perspective of our work. Together, these results suggest a potential link between maternal diet, HSPs, and adipose tissue function.

Keywords: Heat shock proteins; Maternal high-fat diet; Offspring; Sexual dimorphism.