Dairy Milk Casein and Whey Proteins Differentially Alter the Postprandial Lipidome in Persons with Prediabetes: A Comparative Lipidomics Study

Dairy milk, likely through its bioactive proteins, has
been reported
to attenuate postprandial hyperglycemia-induced oxidative stress responses
implicated in cardiovascular diseases (CVDs). However, how its major
proteins, whey and casein, alter metabolic excursions of the lipidome
in persons with prediabetes is unclear. Therefore, the objective of
this study was to examine whey or casein protein ingestion on glucose-induced
alternations in lipidomic responses in adults (17 males and 6 females)
with prediabetes. In this clinical study, participants consumed glucose
alone, glucose + nonfat milk (NFM), or glucose with either whey (WHEY)
or casein (CASEIN) protein, and plasma samples were collected at multiple
time points. Lipidomics data from plasma samples was acquired using
an ultra-high-performance liquid chromatography-high-resolution mass
spectrometry-based platform. Our results indicated that glucose ingestion
alone induced the largest number of changes in plasma lipids. WHEY
showed an earlier and stronger impact to maintain the stability of
the lipidome compared with CASEIN. WHEY protected against glucose-induced
changes in glycerophospholipid and sphingolipid (SP) metabolism, while
ether lipid metabolism and SP metabolism were the pathways most greatly
impacted in CASEIN. Meanwhile, the decreased acyl carnitines and fatty
acid (FA) 16:0 levels could attenuate lipid peroxidation after protein
intervention to protect insulin secretory capacity. Diabetes-associated
lipids, the increased phosphatidylethanolamine (PE) 34:2 and decreased
phosphatidylcholine (PC) 34:3 in the NFM-T90 min,
elevated PC 35:4 and decreased CE 18:1 to a CE 18:2 ratio in the WHEY-T180 min, decreased lysophosphatidylcholine (LPC) 22:6
and LPC 22:0/0:0 in the CASEIN-T90 min, and decreased
PE 36:1 in the CASEIN-T180 min, indicating a decreased
risk for prediabetes. Collectively, our study suggested that dairy
milk proteins are responsible for the protective effect of non-fat
milk on glucose-induced changes in the lipidome, which may potentially
influence long-term CVD risk.