Year: 2020
Type: dissertation
Abstract: Obesity is associated with insulin resistance, which may be underpinned by spill over of excess lipids into ectopic tissue(s) including skeletal muscle. Insulin resistance has been associated with dysregulated protein metabolism and anabolic resistance. The aim of this thesis was to further explore the interactions between insulin and anabolic resistance in human skeletal muscle. This was achieved by using nutritional approaches to alter the availability of substrates proposed to play an important role in mediating this association. In Chapters 3 and 4, the effects of exogenous provision of saturated fatty acids were examined in vivo and in primary human myotubes. Restricting the length of the daily energy intake window, which alters the pattern of exogenous substrate availability, enhances insulin sensitivity in rodents. Preliminary evidence in humans shows beneficial effects of extending the overnight fast and shifting energy intake to earlier in the day. In Chapter 5 and 6, this approach was combined to test the hypothesis that early time-restricted feeding (eTRF) will enhance skeletal muscle insulin and anabolic sensitivity independently of energy balance. In Chapter 3, prior oral ingestion of a saturated fatty acid drink did not impair any index of insulin sensitivity and increased the incorporation of dietary [1-13C] phenylalanine into the myofibrillar pool of middle-aged, overweight/obese males. This was contrary to our hypotheses and suggested a potential role for improved amino acid transport. However, in Chapter 4, pre-treatment of myotubes with 0.25 mM palmitate induced insulin resistance, decreased system A transport of amino acids and tended to downregulate rates of muscle protein synthesis. In Chapter 5, two weeks of restricting daily energy intake to between 08:00 and 16:00 improved skeletal muscle and whole-body insulin sensitivity in healthy males. This was associated with an increased net uptake of branched chain amino acids (an index of anabolic sensitivity) in response to oral protein ingestion. However, eTRF was associated with an involuntary reduction in free-living energy intake and a modest (-1.04 ± 0.71 kg) but significant reduction in body mass. To assess what extent this magnitude of weight loss may have played in our findings, the response of an additional group (matched for age, body mass index and physical activity) to a ~400 kCal daily energy deficit was examined in Chapter 6. Despite comparable weight loss, none of the metabolic improvements associated with eTRF were found. This suggests that the benefits of eTRF are, at least in part, independent of its effects on energy balance. In conclusion, changes in insulin sensitivity may be associated with improvements in anabolic sensitivity under certain conditions. However, in the absence of insulin resistance, elevated lipid availability per se has no detrimental effects on the anabolic response to amino acid ingestion.
Author: Jones, Robert
Institution: University of Nottingham
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7216672437