Human adipose tissue acts as a multi-functional endocrine organ. It has the capacity to control energy homeostasis through changes in peripheral and central mechanisms. However, with increasing weight gain, adipose tissue can more than double its original mass, leading to pathogenic consequences including chronic low grade inflammation and insulin resistance mediated by adipocytokines. These changes within adipose tissue can induce secondary detrimental effects on other organs, such as muscle and liver; which also produce hormones that can affect energy homeostasis. The inflammatory response appears modulated by dietary factors and nutrients, including lipids and glucose, as well as gut derived bacteria, in the form of endotoxin. This thesis sought to investigate the role of nutrients, such as lipids (fatty acids) and glucose, on inflammatory responses, energy expenditure and insulin resistance, in vitro and in whole body human physiology. Specifically, studies examined the impact of duration and frequency of nutrient exposure as well as the impact of novel hormones on central and peripheral metabolism in healthy and insulin resistant states. Nutrients, such as fatty acids, were noted to have an immediate impact on the inflammatory response in both murine and human differentiated pre-adipocytes in vitro. Follow-on whole body physiology studies examined lean and overweight/obese (OW/OB) subjects, given isocaloric high fat meals as either 2 large meals or 5 smaller meals over 24 hours. These studies showed minimal effects on blood profiles in the lean subjects post-meal, whilst the OW/OB subjects took much longer to regain their normal lipid and glucose profiles. However, the frequency of the meals in both cohorts had no specific or significant impact on energy expenditure, inflammation, glucose/insulin levels or lipid profile. Analysis of factors that could affect adipose tissue metabolism and whole body physiology, such as irisin in muscle and FGF21 in liver, highlighted that insulin resistance status, BMI and lipid profiles could, at times, influence their circulating levels. This further highlighted the impact of adipose tissue mass, function and cross-talk on health. In summary, both in vitro and in vivo findings highlighted that ‘over-nutrition’ with lipids and glucose could trigger an inflammatory response, which was more pronounced with weight gain. Secondly, this thesis provided evidence that the frequency or duration of exposure to nutrients was less important than the total amount of nutrients consumed. Taken together, these studies emphasise the importance of focusing on interventions to examine nutrient composition, and to reduce overall nutrient intake, rather than the frequency of meals to improve metabolic health in obesity.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:589905 |
| Date | January 2013 |
| Creators | Piya, Milan Kumar |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/59087/ |
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