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Long chain ω-3PUFA fatty acid supplementation in animal models of diet-induced-obesity has consistently shown to improve insulin sensitivity. The same is not always reported in studies with obese, insulin resistant (IR) subjects. We studied whether high-dose ω-3PUFA supplementation for 3 months improves insulin sensitivity and adipose tissue (AT) inflammation

Long chain ω-3PUFA fatty acid supplementation in animal models of diet-induced-obesity has consistently shown to improve insulin sensitivity. The same is not always reported in studies with obese, insulin resistant (IR) subjects. We studied whether high-dose ω-3PUFA supplementation for 3 months improves insulin sensitivity and adipose tissue (AT) inflammation in severely obese, IR subjects. Thirteen obese, IR subjects underwent 80 mU/m 2· min euglycemic-hyperinsulinemic clamp with subcutaneous (Sc) AT biopsy before and after three months of ω-3PUFA (DHA & EPA, 4g/daily) supplementation. Cytoadipokine plasma profiles were assessed before and after ω-3PUFA. AT-specific inflammatory gene expression was evaluated on Sc fat biopsies. Microarray analysis was performed on the fat biopsies collected during the program. Palmitic and stearic acid plasma levels were significantly reduced (P<0.05) after ω-3PUFA. Gene expression of pro-inflammatory markers and adipokines were improved after ω-3PUFA (P<0.05). Systemic inflammation was decreased after ω-3PUFA, as shown by cytokine assessment (P<0.05). These changes were associated with a 25% increase in insulin-stimulated glucose disposal (4.67±0.62mg/kg ffm•min vs 5.87±0.79mg/kg ffm•min) despite no change in
body weight. Microarray analysis identified 53 probe sets significantly altered post- ω-3PUFA, with APOE being one of the most upregulated genes. High dose of long chain ω-3PUFA supplementation modulates significant changes in plasma fatty acid profile, AT and systemic inflammation. These findings associate with significant improvement of insulin-stimulated glucose disposal. Unbiased microarray analysis of Sc fat biopsy identified APOE as the most differentially regulated gene after ω-3PUFA 22 supplementation. We speculate that ω-3PUFA increases macrophage-derived APOE mRNA levels with anti-inflammatory properties.
ContributorsRau, Cassandra (Author) / Kastanos, Christos (Thesis director) / De Filippis, Eleanna (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description

According to the CDC, obesity has increased from 30.5% to 42.4% over the past 18 years. Western diets (WDs) consist of large portions in high fats, high carbohydrates, excess sugar and high-glycemic foods that can cause metabolic complications and mitochondrial dysfunction. Diet-induced obesity can lead to changes in muscle metabolism

According to the CDC, obesity has increased from 30.5% to 42.4% over the past 18 years. Western diets (WDs) consist of large portions in high fats, high carbohydrates, excess sugar and high-glycemic foods that can cause metabolic complications and mitochondrial dysfunction. Diet-induced obesity can lead to changes in muscle metabolism and muscle fiber phenotypes, which in turn lead to metabolic complications. Muscle fiber phenotype is determined protein isoform-content of myosin heavy chain (MHC). Regular exercise alters mitochondrial content and fat oxidation and shifts MHC proportions under healthy circumstances. However, diet and exercise-driven fiber type shifts in diet-induced obesity are less understood. We designed our experiment to better understand the impact of diet and/ or exercise on fiber type content of gastrocnemius muscle in diet-induced obese mice. Exercise and genistein may be used as a treatment strategy to restore the MHC proportions in obese subjects to that of the lean subjects. We hypothesized that genistein and exercise would have the greatest MHC I change in muscle fiber phenotype of mouse gastrocnemius muscles. Further, we also hypothesized that a standard diet would reverse the expected increase in fast fiber phenotype (MHC IIb). Lastly, we also hypothesized that exercise would also reduce the abundance of MHC IIb. Gastrocnemius muscles were collected from mice, homogenized, run through gel electrophoresis and stained to give muscle fiber proportions. Paired sample t-tests were conducted for differences between the MHC isoforms compared to the lean (LN) and high-fat diet (HFD) control groups. The results showed that genistein and exercise significantly increased the abundance of MHC I muscle fibers (19%, p<0.05). Additionally, diet and exercise restored the muscle fiber phenotype to that of lean control. As expected, HFD obese mice exhibited elevated fast twitch fibers compared to only 3% slow twitch fibers. These findings show the potential for exercise and supplementation of genistein as a strategy to combat diet induced obesity. Future research should aim to understand the mechanisms that genistein acts on to make these changes, and aim to replicate these data in humans with obesity.

ContributorsSodhi, Harkaran (Author) / Katsanos, Christos (Thesis director) / Wang, Shu (Committee member) / Serrano, Nathan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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Description
This is a pilot study testing a new indirect calorimeter device. This project was designed to determine the effect of a high fat versus a standard chow diet and age on the energy gap (the difference between energy intake and energy expenditure). Measurements of energy expenditure and oxygen consumption were

This is a pilot study testing a new indirect calorimeter device. This project was designed to determine the effect of a high fat versus a standard chow diet and age on the energy gap (the difference between energy intake and energy expenditure). Measurements of energy expenditure and oxygen consumption were obtained over a 23-hour period from a group of rats fed a high fat diet and a group of rats fed standard chow diet. The experiments were repeated during an experimental phase for 12 weeks, a phase of caloric restriction for 4 weeks, and a phase of weight regain for 4 weeks. We found energy expenditure and oxygen consumption to decrease in the caloric restriction phase and increase with excessive weight gain. Rats fed a high fat diet and obesity prone rats had a wider energy gap than rats fed a standard chow diet and obesity resistant rats. The caloric restriction phase closed the energy gap between energy expenditure and energy intake for all of the rats. The weight regain phase shifted the rats back into positive energy balance so that the energy intake was greater than the energy expenditure. The rats showed greater weight gain in the weight regain phase than in the experimental phase for all groups of rats. The indirect calorimeter device would require further testing to improve the accuracy of the measurements of respiratory quotient and carbon dioxide production before being used in future clinical research applications. The indirect calorimeter device has the potential to record respiratory quotient and carbon dioxide production.
ContributorsMolenaar, Sydney Alexandra (Author) / Herman, Richard (Thesis director) / Towe, Bruce (Committee member) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05