Effect of long-term dietary fat quality on metabolic health with a special focus on dairy fat
Diet, and particularly dietary fat quality (i.e., fatty acid composition), is a significant modifiable risk factor in the development of metabolic diseases. However, whether the manipulation of long-term dietary fat quality may serve as an effective dietary strategy to mitigate metabolic disease risk during aging is not well defined. Accordingly, this work sought to investigate the role of life-long consumption of bioactive fatty acids from various food sources, and particularly dairy fat, on health maintenance and metabolic disease risk later in life. To address this issue, I assessed how long-term supplementation of dairy fat (butter oil), echium oil, or fish oil to the average U.S. American diet influenced glucose homeostasis, insulin sensitivity, and gut microbiota taxa in male and female mice. An outbred mouse model, which mimics the genetic diversity of humans, was specifically utilized to study the effect of long-term dietary fat quality up to "old age", examining markers of glucose homeostasis at regular intervals. At the end of the study, to examine potential diet-specific mechanisms that may influence metabolic health, fatty acid partitioning in muscle, adipose tissue, liver, and blood was assessed. Investigating the complex relationship between diet, gut bacteria, and metabolic phenotype, I observed that fish oil and echium oil supplementation improved glucose homeostasis over time in males but not in females. Females, however, were consistently more metabolically protected compared to males regardless of age. Furthermore, the apparent sex-dependent metabolic responses to dietary fat quality may in part be explained by distinct tissue-specific partitioning of diet-derived fatty acids. Lastly, sex was found to significantly impact the effect of dietary fat quality on colonic bacteria composition as aging progressed. Cumulatively, long-term dietary fat quality appears to influence gut microbiota and tissue fatty acid stores, in a sex-specific manner, to impact metabolic health and disease risk. My findings therefore have important implications for the design of future dietary strategies to protect metabolic health throughout different life stages.