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  • 12-Week Vegetarian Diet Intervention Effect on Inflammatory Status and Cardio-Metabolic Parameters Rochester, Minn.

    The purpose of this study is to determine if providing a vegetarian diet intervention to obese individuals over a twelve-week period can reduce chronic inflammation as well as improve cardio-metabolic parameters that are precursors to the co-morbidities associated with obesity.

  • Effects of Niacin on Intramyocellular Fatty Acid Trafficking in Upper Body Obesity and Type 2 Diabetes Mellitus Rochester, Minn.

    Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking is responsible for the abnormal response to insulin. Likewise, we do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. We will measure muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates under both saline control (high overnight FFA) and after an overnight infusion of intravenous niacin (lower/normal FFA) to provide the first integrated examination of the interaction between FFA and muscle insulin action from the whole body to the cellular/molecular level. By identifying which steps in the insulin signaling pathway are most affected, we will determine the site-specific effect of ceramides and/or DG on different degrees of insulin resistance.
    Hypothesis 1: Greater trafficking of plasma FFA into intramyocellular DG will impair proximal insulin signaling and reduce muscle glucose uptake.
    Hypothesis 2: Lowering FFA in UBO and T2DM by using an intravenous infusion of niacin will alter trafficking of plasma FFA into intramyocellular ceramides in a way that will improve insulin signaling and increase muscle glucose uptake.
    Hypothesis 3: Lowering FFA in UBO and T2DM by using an intravenous infusion of niacin will alter trafficking of plasma FFA into intramyocellular DG in a way that will improve insulin signaling and increase muscle glucose uptake.

  • Insulin Regulation of Lipolysis and Lipolysis Proteins Rochester, Minn.

    The purpose of this study is to determine whether impaired insulin-induced suppression of lipolysis (as measured by IC50) is related to lipolysis proteins in groups of volunteers known to vary widely with regards to abdominal adipocyte size and regulation of adipose tissue lipolysis, and whether the improved insulin regulation of lipolysis resulting from treatment with the PPARγ agonist pioglitazone, with or without weight loss, can be linked to specific changes in sets of PPARγ-responsive adipocyte lipolysis proteins in UBO adults.



     

     

     

     

     

  • Intramyocellular Fatty Acid Trafficking in Insulin Resistance States - Effects of Intestinal Delivery of Lipids Rochester, Minn.

    Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking is responsible for muscle insulin resistance, although it has been shown that raising FFA with Intralipid can cause muscle insulin resistance within 4 hours. We do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. We propose to alter the profile and concentrations of FFA of healthy, non-obese adults using an overnight, intra-duodenal palm oil infusion vs. an intra-duodenal Intralipid infusion (both compared to saline control). We will compare the muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates, providing the first measure of how different FFA profiles alter muscle FFA trafficking and insulin action at the whole body and cellular/molecular levels. By identifying which steps in the insulin signaling pathway are most affected, we will determine the site-specific effect of ceramides and/or DG on different degrees of insulin resistance.
    Hypothesis 1: Palm oil infusion will result in abnormal FFA trafficking into intra-myocellular ceramides and abnormal insulin signaling.
    Hypothesis 2: Intralipid infusion will result in abnormal FFA trafficking into intra-myocellular saturated DG and abnormal insulin signaling.

  • Laboratory Methodology Development - Muscle Rochester, Minn.

    The purpose of this study is to look for ways to test how muscle tissue differs between people.

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  • “The Perfect Waist Circumference Measuring Device”- Part B Rochester, Minn.

    The purpose of this study is to determine whether abdominal subcutaneous and visceral fat measured by diagnostic imaging correlates with waist circumferences measured by the device.

  • A Single Center, Randomized, Double-blind, Placebo Controlled, Two-way Crossover Study to Determine the Fat Losses in Stool Associated With Alpha-CD Use as Compared to Placebo Using a Radiotracer (FMAT) Rochester, Minn.

    The Investigator hypothesizes that the currently used dose of dietary ingredient alpha-cyclodextrin (α-CD) will result in greater loss of dietary fat in the stool compared with placebo. The proposed studies will address the degree to which α-CD increases dietary fat loss. The Investigator will conduct the study and analyze the samples at Mayo Clinic in Rochester, Minnesota.

  • Adipose Tissue Characteristics on Inflammatory Markers, Mediators of Inflammation and Insulin Signaling Before and After Weight Loss in Different Obesity Phenotypes Rochester, Minn.

    The purpose of this study is to see why the ability of fat cells to respond to insulin is different depending on body shape and how fat tissue inflammation is involved.

  • Inflammatory Status of Obese Vegetarians Compared to Obese Non-vegetarians Rochester, Minn.

    The purpose of this study is to learn if eating a vegetarian diet changes the make up of a person's fatty acids as well as their levels of inflammation.

  • Intramyocellular Fatty Acid Trafficking in Insulin Resistance States Rochester, Minn.

    Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM), whereas lower body obesity (LBO) is characterized by near-normal insulin sensitivity. It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking differs between different obesity phenotypes. Likewise, we do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. By measuring muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates we will provide the first integrated examination of the interaction between FFA and muscle insulin action from the whole body to the cellular/molecular level. By identifying which steps in the insulin signaling pathway are most affected, we will determine the site-specific effect of ceramides and/or DG on different degrees of insulin resistance.
    Hypothesis 1: Greater trafficking of plasma FFA into intramyocellular DG will impair proximal insulin signaling and reduce muscle glucose uptake.
    Hypothesis 2: Greater trafficking of plasma FFA into intramyocellular ceramides will impair distal insulin signaling and reduce muscle glucose uptake.
    Hypothesis 3: The uptake of plasma FFA destined to intramyocellular triglycerides is increased relative to FFA concentrations in UBO and T2DM compared with LBO.

  • Mediators of insulin resistance in women with a history of gestational diabetes mellitus Rochester, Minn.

    Women with gestational diabetes mellitus (GDM) are likely to have insulin resistance that persists long after pregnancy, resulting in greater risk of developing type 2 diabetes mellitus (T2DM). The study will compare women with and without a previous diagnosis of GDM to determine if women with a history of GDM have abnormal fatty acid metabolism, specifically impaired adipose tissue lipolysis. The study will aim to determine whether women with a history of GDM have impaired pancreatic β-cell function. The study will determine whether women with a history of GDM have tissue specific defects in insulin action, and also identify the effect of a history of GDM on intracellular insulin signaling in subcutaneous adipose tissue.

  • Muscle and Adipose Trafficking of Fatty Acids Under Hypoinsulinemic and Fed Conditions Rochester, Minn.

    The goal of this study is to gain further insight into how different sources of fatty acids presented during two different metabolic challenges are trafficked by subcutaneous adipose tissue and skeletal muscle in a cohort of human adults with known variability in fat metabolism and insulin sensitivity. Tracking the allocation of these fatty acids into adipose and skeletal muscle lipid pools during metabolic states representative of fasted (elevated plasma free fatty acids and absent meal-derived fatty acids) and fed states (low plasma free fatty acids and high meal-derived fatty acids) can help elucidate rate-limiting steps in the biochemical pathways of fatty acid metabolism, ultimately providing insight into the mechanisms related to the development of such metabolic complications as obesity and insulin resistance. 

     

  • Pivotal Aspiration Therapy With Adjusted Lifestyle Therapy Study (PATHWAY) Rochester, Minn.

    This research study is being performed to find out if a new device, AspireAssist Aspiration Therapy System, can help people with obesity to lose weight without causing too many side effects.

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