All ETDs from UAB

Advisory Committee Chair

Stephen Watts

Advisory Committee Members

Gregory Kennedy

Mickie L Powell

Daniel L Smith Jr

Document Type

Thesis

Date of Award

2020

Degree Name by School

Master of Science (MS) College of Arts and Sciences

Abstract

Obesity manifests physiologically in multiple organ systems of the body, typically increasing the risk of developing cardiometabolic disorders. Researchers have questioned the causative role that western dietary patterns have on disease pathogenesis and have speculated that quality and quantity of dietary fats and/or carbohydrates have a predictive role in the development of these disorders. Standard reference diets such as the AIN-93 rodent diet have historically been used to promote optimal animal model health and reduce variation of results across experiments. These diets have been invaluable to murine research; however, their translational value in studying human nutrition-related pathologies is limited. Early nutrition studies of diet-induced obesity (DIO) demonstrated that high-fat intake induces DIO, and high-fat diets (HFDs) became a classic tool to investigate obesity. These murine diets, however, lack standardization in terms of source and quantity of fats, and the most reliable HFDs that induce obesity contain levels of fat up to 45-60% (kcal), much higher than reported human intake of 33-35% (kcal). More recently, a few researchers have addressed these concerns by formulating experimental diets that reflect mean human macro- and micronutrient consumption levels described by the National Health and Nutrition Examination Survey (NHANES). These diets attempt to integrate relevant sources and levels of nutrients; however, they do not include high fructose corn syrup (HFCS) as a source of carbohydrate. To address these concerns, we iii formulated a modified Standard American Diet (mSAD) that incorporates human-relevant levels and sources of nutrient classes, including dietary HFCS. C57BL/6J male mice proffered the mSAD for 15 weeks displayed a phenotype consistent with metabolic syndrome, exhibiting increased adiposity, fasting hyperglycemia with impaired glucose and insulin tolerance. Metabolic alterations were visualized at the tissue level as crown-like structures (CLS) in adipose tissue and fatty acid deposition in the liver. Biochemical changes in tryptophan (Trp) signaling concurrent with alterations in gut microbes suggests that microbial metabolism may play a role in coordination of responses among multiple physiological systems. Diet quality definitively affects metabolic homeostasis, emphasizing the importance of developing relevant pre-clinical diets to investigate chronic diseases highly impacted by western dietary consumption patterns.

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