The effects of physical activity and diet change on intracellular lipids and metabolism in mice with diet-induced obesity
Year: 2014
Type: dissertation
Abstract: High energy intake, sedentary lifestyle, overweight and obesity are all considered to predispose to metabolic syndrome and the development of type 2 diabetes. Under these physiological conditions, excess lipids are stored ectopically in insulin-sensitive tissues, such as skeletal muscle and the liver. Several studies have demonstrated an association between elevated amounts of intramyocellular lipids (IMCL) and insulin resistance, which is one of the hallmarks of the metabolic syndrome and type 2 diabetes. However, the cellular pathogenesis leading to insulin resistance remains a matter of debate. Physical activity is shown to be one of the most potent remodelers of the lipid metabolism in skeletal muscle. The aim of this thesis was to investigate the effects of combined dietinduced obesity, voluntary wheel running and diet change intervention on intracellular lipid accumulation and its role in the development of insulin resistance in the skeletal muscle and livers of C57BL/6J mice. In order to induce a condition mimicking the metabolic syndrome, male mice (n=90) were fed with a high-fat diet (60% energy from fat). These animals manifested typical characteristics of the metabolic syndrome after the 19-week experiment. Longterm high-fat feeding increased intracellular lipid accumulation and the amount of the lipid droplet-associated protein perilipin 5 in skeletal muscle, as well as in the liver. Surprisingly, an increased effect of oxidative capacity in skeletal muscle was observed, whereas in the liver oxidative capacity decreased with high-fat feeding. In addition, muscle capillarization seems to have even increased with the high-fat diet. In conclusion, it was discovered that many of the investigated variables benefit from voluntary physical activity, with or without a high-fat diet, and surprisingly the results showed similar positive effects even with high-fat diet alone (i.e. increased energy supply). However, the strongest beneficial effects in many of the variables were seen after diet change intervention, with no additional effect of physical activity. Thus, diet change intervention alone seems to play a more critical role in the prevention of insulin resistance than physical activity alone. A detailed understanding of these cellular mechanisms and pathways involved in obesity and complex metabolic diseases contributes to finding an efficient means of attenuating their global prevalence.
Author: Rita Rinnankoski‐Tuikka
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: Jyväskylän Yliopisto
OpenAlex ID: W2226803871