Interesterified palm oil consumption drives brown adipose tissue whitening and functional impairment in high-fat diet mice

This study investigates how the consumption of interesterified palm oil (IPO) affects the metabolic and morphological features of brown adipose tissue (BAT) in C57BL/6 mice fed a high-fat diet. Mice were divided into four groups: control, high-fat diet (lard), high-fat diet with palm oil (PO; HFP) and high-fat diet with IPO (HFI). The HFP and HFI groups exhibited significant body weight gain, increased fat mass and impaired glucose metabolism. Histological analyses revealed lipid infiltration in BAT, leading to structural remodelling from multilocular to unilocular adipocytes, which are hallmark features of the whitening process. This morphological shift was accompanied by reduced nuclear density and impaired vascularisation. Gene expression analysis indicated downregulation of key thermogenic markers, including <i>Ucp1</i>, <i>Pparγ</i> and <i>Prdm16</i>, especially in the HFI group. Increased expression of endoplasmic reticulum stress markers such as <i>Chop</i> and <i>Atf4</i> and inflammatory cytokines (TNF-<i>α</i> and IL-6) highlighted the pro-inflammatory and pro-apoptotic microenvironment induced by PO and IPO. These changes culminated in a loss of BAT thermogenic capacity, as evidenced by decreased uncoupling protein 1 levels and impaired adaptive thermogenesis. Our findings underscore the detrimental effects of PO, mainly IPO, on BAT functionality, exacerbating obesity-related metabolic dysfunctions such as insulin resistance and glucose intolerance. The results emphasise the need for caution in the dietary use of these fats, particularly in ultra-processed food formulations, given their potential role in promoting adipose tissue remodelling and metabolic imbalances.