The long-term goal of our research is to understand how obesity, specifically upper body obesity (UBO), causes insulin resistance and the other health problems such as Type 2 Diabetes. Our focus has been on how free fatty acid (FFA) release from adipose tissue lipolysis in humans affect the functioning of other tissues (lipotoxicity).
The specific aims of this proposal are to: 1) determine whether insulin-resistant UBO have reduced muscle glucose uptake in response to exercise compared with insulin sensitive normal weight control volunteers; 2) assess whether the exercise signaling pathway is intact in insulin-resistant UBO compared with insulin sensitive normal weight control volunteers; 3) measure whether the trafficking of plasma FFA-palmitate into lipid intermediates is altered in insulin resistant UBO compared with insulin sensitive, normal weight control volunteers; and 4) determine whether overnight, modest increases in plasma FFA using an intra-duodenal palm oil infusion impairs exercise-stimulated muscle glucose uptake in insulin sensitive, normal weight volunteers. We will measure exercise-stimulated muscle glucose uptake in vivo and assess some of the muscle signaling proteins involved in GLUT4 translocation in insulin sensitive lean and insulin resistant UBO that are matched for fitness. We will also measure whether raising FFA in a physiological pattern using palm oil reduces exercise-stimulated muscle glucose uptake. Our hypothesis is that the distal steps involved in muscle glucose transport are altered in UBO humans (e.g. exercise-stimulated muscle glucose uptake is also impaired in UBO) and that these defects are responsible for the apparent insulin resistance with regards to muscle glucose uptake. Combined, we believe these studies will offer insights as to why UBO are insulin resistant and provide information on what therapeutic strategies to treat muscle insulin resistance are most promising.
We wish to understand why people who gain weight primarily in the abdominal area are more prone to illnesses such as diabetes. We know that those with excess upper body fat (upper body obesity) are unable to take up sugar normally in muscle tissue, which then effects how the rest of our body is able to metabolize sugars. The experiments we propose will measure whether exercise is able to normalize sugar uptake into muscle in adults with upper body obesity and whether increases in blood fats will reduce the ability of exercise to stimulate uptake of sugar into leg muscle.
| Chung, Jin Ook; Koutsari, Christina; Blachnio-Zablieska, Agnieszka Urszula et al. (2018) Effects of meal ingestion on intramyocellular ceramide concentrations and fractional de novo synthesis in humans. Am J Physiol Endocrinol Metab 314:E105-E114 |
| Lu, Jin; Allred, Carolyn C; Jensen, Michael D (2018) Human adipose tissue protein analyses using capillary western blot technology. Nutr Diabetes 8:26 |
| Bray, George A; Heisel, William E; Afshin, Ashkan et al. (2018) The Science of Obesity Management: An Endocrine Society Scientific Statement. Endocr Rev 39:79-132 |
| Espinosa De Ycaza, A E; Donegan, D; Jensen, M D (2018) Long-term metabolic risk for the metabolically healthy overweight/obese phenotype. Int J Obes (Lond) 42:302-309 |
| Morgan-Bathke, Maria; Harteneck, Debra; Jaeger, Philippa et al. (2017) Comparison of Methods for Analyzing Human Adipose Tissue Macrophage Content. Obesity (Silver Spring) 25:2100-2107 |
| Santosa, Sylvia; Bush, Nikki C; Jensen, Michael D (2017) Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage. J Clin Endocrinol Metab 102:3056-3064 |
| Chung, Jin Ook; Koutsari, Christina; Blachnio-Zabielska, Agnieszka U et al. (2017) Intramyocellular Ceramides: Subcellular Concentrations and Fractional De Novo Synthesis in Postabsorptive Humans. Diabetes 66:2082-2091 |
| Lu, Jin; Varghese, Ron T; Zhou, Lianzhen et al. (2017) Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146. Metabolism 68:55-63 |
| Anthanont, P; Ramos, P; Jensen, M D et al. (2017) Family history of type 2 diabetes, abdominal adipocyte size and markers of the metabolic syndrome. Int J Obes (Lond) 41:1621-1626 |
| Søndergaard, Esben; Espinosa De Ycaza, Ana Elena; Morgan-Bathke, Maria et al. (2017) How to Measure Adipose Tissue Insulin Sensitivity. J Clin Endocrinol Metab 102:1193-1199 |
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