Full-fat dairy milk vs. isolated free nutrient blend on postprandial protein metabolism and inflammatory markers in adults with overweight and obesity

Excess adiposity is linked to anabolic resistance by blunting the postprandial myofibrillar protein synthetic response to protein ingestion. Full-fat dairy milk may overcome this resistance via a matrix combining high-quality protein with anti-inflammatory lipids. Therefore, we compared the effects of ingesting full-fat dairy milk versus a non-dairy macronutrient match isolated blend on the regulation of postprandial myofibrillar and mitochondrial protein synthesis rates and markers of systemic (i.e., IL-6 and TNF-α) and muscle-related inflammation (i.e., NF-κB, NLRP3, TLR4, and MyD88). Twenty-two obese and overweight adult males and females (BMI = 31.1 ± 3.7 kg m⁻²; aged 35.3 ± 13.2 y) were block-randomized to consume 16-oz of full-fat dairy milk (MILK; n = 12) or a non-dairy macronutrient match isolated blend (ISO; n = 10). Blood, breath, and muscle biopsies were collected at rest and after treatment ingestion during primed constant infusions of L-[ ring -²H₅]phenylalanine and L-[1–¹³C]leucine. Myofibrillar protein synthesis was elevated above baseline during the 0–300 min postprandial periods for both ISO ( P < 0.001) and MILK ( P = 0.05), with a more significant increase in ISO compared to MILK ( P = 0.011). There was no change in postprandial mitochondrial protein synthesis from baseline regardless of condition ( P > 0.05). Acute intramuscular NF-κB phosphorylation was elevated at 300 min postprandially in MILK ( P = 0.002), with no other changes in systemic or muscle inflammatory markers in either group (all, P < 0.05). Full-fat dairy stimulated postprandial myofibrillar protein synthesis less effectively than a matched isolated blend and increased intramuscular NF-κB phosphorylation without modulating other markers of systemic inflammation. Clinical trial https://clinicaltrials.gov/study/NCT04216004 .