4. Discussion
pre-AD, hyperinsulinemia
INFLAMMATION, PATHOPHYSIOLOGY, HYPERINSULINEMIA, CHRONIC INFLAMMATION, OXIDATIVE STRESS, DYSLIPIDEMIA
This work is the first cross-over study which reports the association between specific serum proteins and individual bile acids in hyperinsulinemia subjects after the consumption of adequate or high dairy intake. The main finding is that higher consumption of dairy products modifies the association between 7αC4—a biomarker for bile acid synthesis—and serum proteins involved in the immune system and lipid metabolism. Importantly, 7αC4 correlated positively with proteins associated with pathways for remodeling high-density lipoprotein particles and facilitating the reverse transport of cholesterol exclusively in the post-HD condition.Specifically, the post-HD group exhibited higher dietary cholesterol, SFA, DPA, TFA, MUFA, and PUFA levels compared to the pre-HD, pre-AD and post-AD groups [Interestingly, a positive correlation was observed between 7αC4 and triglyceride levels in both the pre-AD and post-HD conditions. Concurrently, 7αC4 exhibited a positive correlation with proteins involved in cholesterol and lipoprotein metabolic processes in the pre-AD condition. The proteins associated with these biological processes were APOC3, APOC1, and APOL1. These proteins are known components of lipoproteins responsible for transporting lipids, such as cholesterol and triglycerides, in the bloodstream. APOC3 and APOC1 play central roles in HDL metabolism [Further, a positive association between 7αC4 and proteins involved in high-density lipoprotein particle remodeling and reverse cholesterol transport were observed after high dairy intake (post-HD). Reverse cholesterol transport is a critical process that involves the transportation of excess cholesterol from peripheral tissues, including arterial walls, back to the liver for eventual elimination from the body. This process is largely facilitated by HDL, which play a central role in collecting cholesterol from tissues and transporting it to the liver [In addition to the association of 7αC4 with HDL lipoprotein particle remodeling and cholesterol clearance processes after consumption of high dairy intake, 7αC4 negatively correlated with serum proteins involved in complement activation and the killing of cells from other organisms. Specifically, proteins involved in biological processes like CFD, C9, and C8B correlated negatively with 7αC4. Notably, the occurrence of oxidative harm to cell membranes in various organs has the potential to increase the initiation of the classical complement pathway. The complement system not only enhances the body’s ability to clear pathogens and stimulate inflammation, but also helps in the removal of damaged cells [There are several limitations in our study. First, the small sample size may have limited the statistical power and sensitivity, potentially indicating our ability to detect correlations between different serum bile acids and various proteins. Second, the study participants were overweight/obese adults with hyperinsulinemia, and it remains uncertain whether the findings are representative of other chronic conditions that may impact dyslipidemia, oxidative stress, and chronic inflammation. Third, the present study focused only on 7αC4 as other bile acids did not exhibit changes across different conditions. Another limitation pertains to the short study duration. Further, changes in bile acids may require a more extended period of higher dairy consumption to become significant. Thus, extending the period of higher dairy intake may show more comprehensive insights into the beneficial effects of dairy products on the pathophysiology of hyperinsulinemia and the relationship between bile acids and serum proteins. The potential for residual confounding factors is possible. However, the current study design was a randomized controlled trial which reduces potential for confounding by generating groups that are comparable with respect to known and unknown confounding variables.