An examination of the metabolic, cholesterogenic and lipogenic effects of whey protein isolate in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality in women of reproductive age, with a prevalence of around 18% based on the current Rotterdam diagnostic criteria. Dyslipidemia as a result of altered lipid metabolism is common in this population. Thus, women with PCOS have an increased risk of non-alcoholic fatty liver disease (NAFLD) development. Study design: The 3x2 factorial study aimed to understand the in vivo and in vitro effects of 40-day whey protein isolate (WPI) supplementation in 14 women with and without PCOS. A two-way mixed model ANOVA was used to compare alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglycerides (TG) before, during and after 40 days of 35g WPI ingestion. To correlate these findings, HepG2 cells were grown under normal conditions before 48-hour exposure to plasma from women in the previously described clinical study. An independent samples t-test was used to assess changes in gene expression of DGAT2, FAS, ACAT1, HMGCR, LDLr, LPL, and HSL from days 0, 20 and 40 compared to a negative control. A one-way ANOVA was run to compare differences in hepatic lipid accumulation between plasma source groups. Results: ALT did not differ among days [F(2,24) = 0.24, p = .79] or between groups [ F(1,12) = 0.57, p = .47]. There was a significant effect of condition (CON vs. PCOS) on mean TC concentration (mean difference = 32.918, SE = 11.63 mg/dL, p = .015, η2 = .400), but the main effect of day was not significant [F(2,24) = 0.56, p = .58]. On day 40, significant differences were observed in the mRNA expression of DGAT2, FASN, LDLr, and LPL (p < .05 for all) in those cells treated with plasma from the CON or PCOS group. A similar relationship was not observed for HMGCR, HSL, or ACAT1. Lipid accumulation decreased in both groups (NS), but the effect was not maintained. Conclusion: This 40-day WPI supplementation study provides evidence that key regulators of lipid metabolism in women with PCOS may be affected by long-term WPI supplementation, but further exploration is needed to enhance our understanding of changes in the in vivo environment.