Milk fat-globules derived from whey protein phospholipid concentrate prevent high-fat diet induced cognitive impairment in wistar rats in a manner associated with increased brain neuronal connectivity and sphingolipid clearance

Whey protein phospholipid concentrate (WPPC), a co-product of whey protein processing, is enriched in milk fat globules containing phospholipids, glycoconjugates and sugar monomers (e.g. sialic acid) critical to myelin synthesis in the brain. We hypothesized that WPPC will prevent cognitive impairment induced by a high fat (HF) diet by promoting myelin turnover and improving neuronal connectivity between the entorhinal cortex-hippocampal circuitry involved in encoding memory. Rats were randomized from weaning to ∼6.5 months of age to the following diets: a low-fat (LF) diet containing 10 % fat by weight, a HF diet containing 45 % fat by weight to induce cognitive impairment, and a HF diet containing either 1.6 % (HF1.6) or 10 % (HF10) WPPC by weight (n = 12 per group). Rats received cognitive testing after 1.5 and 4 months of dietary intervention, then implanted with chronic bipolar electrodes to measure axonal evoked responses within the entorhinal cortex-hippocampal circuitry by stimulating the entorhinal cortex, measuring the half-max response in the hippocampus, and comparing the half-max response to a measurement made approximately one hour later (as a marker of memory storage potential). Hippocampal phospholipid and sphingolipid components of myelin were quantified. At 4 months, rats on the HF diet performed significantly worse on cognitive testing than rats on the LF, HF1.6 and HF10 diets. These effects were linked to slight improvements in the evoked response associated with hippocampal-dependent memory storage. Additionally, hippocampus sphingolipids were higher in rats on the HF diet compared to the LF, HF1.6 and HF10 groups. These findings demonstrate that WPPC prevented cognitive impairment induced by a HF diet by regulating entorhinal cortex-hippocampal circuitries associated with memory storage, through modulating myelin turnover.