Dairy Product Consumption and Metabolic Health
Creators: Yuzbashian Sharifabad, Emad
Publisher: name: University of Alberta Library
Year: 2024

<p>The increasing prevalence of overweight and obesity worldwide has raised the alarm for urgently needed preventative strategies to counter the trend of increased risk associated with these conditions, including type 2 diabetes (T2D) and metabolic-associated fatty liver disease (MASLD). Energy imbalance and suboptimal diets can induce these conditions. The contribution of dairy products remains debatable in this regard. Dairy products are quite heterogeneous regarding nutrient composition, physical state, and structure, and their effect on health will likely vary.<br>
In this dissertation, I aim to unravel the effects of different types of dairy foods on obesity-associated metabolic outcomes. It covers a prospective cohort study, a meta-analysis of observational studies, a preclinical trial, and a scoping review. I hypothesize that the impact of dairy consumption on metabolic health varies significantly based on the type of dairy product, fermentation status, and food matrices, and that dairy products can attenuate the metabolic consequences of a Western-style diet.<br>
To address the first objective, the association of dairy consumption patterns with the incidence of T2D among ATP participants was evaluated. The average follow-up time was 5.2 years. Detailed dietary intake information was assessed using a validated food-frequency questionnaire; health outcomes were collected using a self-report questionnaire. PCA was used to extract the dairy consumption patterns. A mixed intake of low and whole-fat milk decreased the risk of T2D by 36% in males. This effect was more pronounced in high-risk groups such as those with obesity. <br>
The second objective was to document the associations between total dairy intake, intake from specific dairy foods, and MASLD. A meta-analysis of 11 observational studies with 43,649 individuals was performed. Pooled data indicated that high dairy product consumption was significantly inversely associated with MASLD risk. Milk and yogurt consumption were associated with 14% and 12% lower risk of MASLD, respectively. However, no significant association was seen with cheese intake. <br>
Objective 3 was conducted to elucidate the mechanism of action of low/non-fat dairy matrices on metabolism in a mouse model of obesity. Male C57BL/6 obese mice were fed an HFD and subsequently allocated into treatment groups receiving either fat-free milk, plain non-fat yogurt, or reduced fat (19%) cheddar cheese at 10% of daily caloric intake for 8 weeks. Milk-treated mice showed high energy expenditure and lower weight gain. Evidence from immunoblotting of metabolic pathways suggested the activation of brown adipose tissue through the SIRT1-PPARγ-PGC1α pathway, which includes increasing UCP1, one of the major thermogenic regulators. Milk consumption also markedly decreased hepatic steatosis, confirmed by a lower triglyceride content. Immunoblotting evidence supports that the mechanism involved lipogenesis suppression and enhanced liver fat oxidation. Mice in the milk group showed improved glucose homeostasis, possibly by ameliorating the hepatic insulin signaling pathway and suppressing gluconeogenic enzymes. While yogurt supplementation improved hepatic steatosis and insulin sensitivity, these beneficial effects were less potent than milk. Yogurt increased energy expenditure suggesting increased BAT activity. Supplementation with cheese had a more neutral effect, with a modest reduction of body weight gain. Gut microbiota analysis indicated increased beneficial bacteria such as Streptococcus in the yogurt and Anaerotignum in the milk groups. Serum and liver lipidomics demonstrated that milk and yogurt consumption significantly reduced diacylglycerides and increased levels of beneficial lipid species, indicating enhanced lipid metabolism and reduced hepatic lipotoxicity.<br>
Objective 4 was a scoping review summarizing studies on the impact of dairy products on phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) concentrations in humans and animals. Fifteen publications were included in this review. Generally, total phospholipids were stable after dairy consumption, while specific PC and LPC species increased, especially those with dairy fatty acid biomarkers, including C15:0 and C17:0. In animal models, dairy consumption also resulted in increased fecal excretion of phospholipids and significant changes in certain liver and serum PC and LPC species.<br>
The combination of results from this research, along with a review of the current literature, supports my hypothesis that dairy products can mitigate the adverse effects of a Western diet on metabolic health with shared and unique mechanisms that may depend on the dairy matrix. Specifically, the positive effects of milk and yogurt in elevating energy expenditure, insulin sensitivity, and lowering liver fat underscore the importance of such dairy products in dietary recommendations to prevent T2D and MASLD.</p>