The effect of carbohydrate on cardiovascular disease risk factors at rest and during exercise with an exploration of sex differences

: (Alternative Format Thesis)

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide. Exercise provides a way to improve almost all the modifiable risk factors of CVD. Nutrition, in particular
carbohydrate intake, surrounding exercise may alter lipid metabolism and substrate use, thereby changing the metabolic effects of exercise. However, the exact mechanisms of how alterations to substrate use during exercise influence metabolism and cell signalling is not fully understood. Whether these alterations can reduce LDL-C concentrations and thus CVD risk is unknown. Moreover, due to potential sex differences in substrate oxidation, to fully understand the implications of substate use on risk of CVD and metabolic diseases, biological sex must be taken into consideration. Historical data demonstrate clear differences in physiology between males and females, one difference being the cyclical rhythms in sex hormones in females. These differences may lead to differences in resting and exercise metabolism, and thus disease risk, which may justify different approaches to disease prevention. Therefore, the aim of this thesis was to explore the effect of carbohydrate on lipid metabolism at rest and during exercise, while also exploring potential sex differences. Sex differences in the variability of resting metabolism was explored and demonstrate similar within- and between- individual variability in males compared with females, despite higher variability in sex hormones in females. Responses to carbohydrate ingestion at rest demonstrate that males display a higher triglyceride response compared to females without detectable sex differences in other aspects of whole body and hepatic lipid metabolism. In addition, we demonstrate that while carbohydrate ingestion reduces fat oxidation and exercise-induced skeletal muscle AMPK signalling during an acute bout of exercise, this does not lead to acute changes in energy intake or meaningful changes in lipid profiles, glycaemic control or classical CVD risk factors over 12 weeks of exercise compared to fasted-state exercise. The data from this thesis demonstrate that sex differences in fasting plasma metabolite concentrations and the metabolic response to carbohydrate during exercise are minimal and justify the inclusion of females in metabolic research in these areas and the extrapolation of single sex data to both sexes. In addition, we demonstrate that
carbohydrate acutely affects hepatic lipid metabolism and skeletal muscle signalling, but this does not appear to lead to distinguishable changes in classical CVD risk factors over time.

Date of Award	19 Feb 2025
Original language	English
Awarding Institution	University of Bath
Supervisor	Javier Gonzalez (Supervisor), James Betts (Supervisor) & Francoise Koumanov (Supervisor)