Interesterified palm oil-induced maternal metabolic dysfunction programs early-life insulin resistance and inflammation in mouse offspring in a sex-specific manner.

Interesterified fats have become a common source of fat for the food industry, however, their role in metabolic programming remains poorly understood. This study investigated whether maternal consumption of a normocaloric diet containing interesterified palm oil, starting prior to conception until the end of lactation, could trigger metabolic impairments in young offspring. Female C57BL/6J mice were fed a normocaloric diet containing either palm oil (P) or interesterified palm oil (INP) for four weeks before mating and throughout gestation and lactation. After the preconceptional period, the dams' metabolic profile was evaluated. At postnatal day 30 (d30), male and female offspring were evaluated for glucose and insulin tolerance, tissue-specific insulin signaling and inflammatory profile, and hypothalamic neuropeptide expression. Even before mating, INP-fed dams exhibited hyperphagia, increased body weight, reduced energy expenditure, increased NPY and decreased POMC neuronal labeling in the hypothalamus. In the offspring, maternal INP exposure induced a pronounced sexual dimorphism, despite no differences in body weight or adiposity. Female offspring showed systemic glucose intolerance and impaired insulin sensitivity, supported by reduced pAKT levels in skeletal muscle and white adipose tissue (gWAT). In contrast, male offspring maintained functional glucose tolerance but showed tissue-specific molecular impairments, including reduced hepatic pAKT levels and a paradoxical compensatory increase in gWAT pAKT levels. Both sexes exhibited a pro-inflammatory profile, with upregulation of Tnf across all tissues and an increase in Il-6 and Il-1β in gWAT and the hypothalamus. These findings demonstrate that INP disrupts maternal neuroendocrine homeostasis and predisposes offspring to early-life insulin resistance, glucose intolerance, specifically in female offspring, and systemic inflammation.