Michael D. Jensen, M.D.

The purpose of this study is to provide the first integrated examination of the interaction between muscle insulin action and exercise-stimulated muscle glucose uptake in obesity from the whole body to the cellular/molecular level.

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.



 

This study is designed to understand the control of adipocytle lipolysis in femoral and abdominal adipose tissue beds in response to insulin amongst humans with a wide range of insulin senstivity.

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.

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

The purpose of this study seeks to understand the ability of niacin to suppress adipose tissue lipolysis in different adipose tissue depots amongst humans who are normal weight and humans who have obesity. 

The purpose of this study is to understand the differential response of lipolysis in obesity to interventions that should stimulate lipolysis and intracellular lipolysis proteins.

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.

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.

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.

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.

The primary purpose of this research study is to collect a large enough sample of fat cells (preadipocytes) and blood from patients undergoing surgery to establish a bank of samples for use by researchers to begin to understand what factors regulate the ability of fat tissue to grow better in some people than others.