Translational Medical Research Commons^™

Human Visfatin Expression: Relationship To Insulin Sensitivity, Intramyocellular Lipids, And Inflammation, Vijayalakshmi Varma, Aiwei Yao-Borengasser, Neda Rasouli, Angela M. Bodles, Bounleut Phanavanh, Mi-Jeong Lee, Tasha Starks, Leslie M. Kern, Horace J. Spencer Iii, Robert E. Mcgehee Jr., Susan K. Fried, Philip A. Kern

Clinical and Translational Science Faculty Publications

Context: Visfatin (VF) is a recently described adipokine preferentially secreted by visceral adipose tissue (VAT) with insulin mimetic properties.

Objective: The aim of this study was to examine the association of VF with insulin sensitivity, intramyocellular lipids (IMCL), and inflammation in humans.

Design and Patients: VF mRNA was examined in paired samples of VAT and abdominal sc adipose tissue (SAT) obtained from subjects undergoing surgery. Plasma VF and VF mRNA was also examined in SAT and muscle tissue, obtained by biopsy from well-characterized subjects with normal or impaired glucose tolerance, with a wide range in body mass index (BMI) and …

Divergent Effects Of Peroxisome Proliferator-Activated Receptor Γ Agonists And Tumor Necrosis Factor Α On Adipocyte Apoe Expression, Lili Yue, Neda Rasouli, Gouri Ranganathan, Philip A. Kern, Theodore Mazzone

Clinical and Translational Science Faculty Publications

ApoE is expressed in multiple mammalian cell types in which it supports cellular differentiated function. In this report we demonstrate that apoE expression in adipocytes is regulated by factors involved in modulating systemic insulin sensitivity. Systemic treatment with pioglitazone increased systemic insulin sensitivity and increased apoE mRNA levels in adipose tissue by 2-3-fold. Treatment of cultured 3T3-L1 adipocytes with ciglitazone increased apoE mRNA levels by 2-4-fold in a dose-dependent manner and increased apoE secretion from cells. Conversely, treatment of adipocytes with tumor necrosis factor (TNF) α reduced apoE mRNA levels and apoE secretion by 60%. Neither insulin nor a peroxisome …

Insulin Sensitivity Following Agent Orange Exposure In Vietnam Veterans With High Blood Levels Of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin, Philip A. Kern, Sufyan Said, William G. Jackson Jr., Joel E. Michalek

Clinical and Translational Science Faculty Publications

Our objective was to determine whether insulin sensitivity was related to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Vietnam veterans exposed to Agent Orange. Air Force veterans of Operation Ranch Hand, the unit responsible for spraying Agent Orange and other herbicides in Vietnam from 1962 to 1971, and comparison veterans who did not spray herbicides were included. We measured insulin sensitivity (S_I) using a frequently sampled iv glucose tolerance test in a matched study of 29 matched pairs of veterans and a quantitative insulin sensitivity check index (QUICKI) based on fasting glucose and insulin in 71 matched pairs. No group differences were …

Adiponectin Expression From Human Adipose Tissue: Relation To Obesity, Insulin Resistance, And Tumor Necrosis Factor-Α Expression, Philip A. Kern, Gina B. Di Gregorio, Tong Lu, Negah Rassouli, Gouri Ranganathan

Clinical and Translational Science Faculty Publications

Adiponectin is a 29-kDa adipocyte protein that has been linked to the insulin resistance of obesity and lipodystrophy. To better understand the regulation of adiponectin expression, we measured plasma adiponectin and adipose tissue adiponectin mRNA levels in nondiabetic subjects with varying degrees of obesity and insulin resistance. Plasma adiponectin and adiponectin mRNA levels were highly correlated with each other (r = 0.80, P < 0.001), and obese subjects expressed significantly lower levels of adiponectin. However, a significant sex difference in adiponectin expression was observed, especially in relatively lean subjects. When men and women with a BMI2were compared, women had a twofold higher percent body fat, yet their plasma adiponectin levels were 65% higher (8.6 ± 1.1 and 14.2 ± 1.6 μg/ml in men and women, respectively; P < 0.02). Plasma adiponectin had a strong association with insulin sensitivity index (S_I) (r = 0.67, P < 0.0001, n = 51) that was not affected by sex, but no relation with insulin secretion. To separate the effects of obesity (BMI) from S_I, subjects who were discordant for S_I were matched for BMI, age, and sex. Using this approach, insulin-sensitive subjects demonstrated a twofold higher plasma level of …

Thiazolidinediones Inhibit Lipoprotein Lipase Activity In Adipocytes, Subramanian Ranganathan, Philip A. Kern

Clinical and Translational Science Faculty Publications

The thiazolidinediones troglitazone and BRL 49653 improve insulin sensitivity in humans and animals with insulin resistance. Adipose tissue lipoprotein lipase is an insulin-sensitive enzyme. We examined the effects of thiazolidinediones on lipoprotein lipase expression in adipocytes. When added to 3T3-F442A, 3T3-L1, and rat adipocytes in culture, troglitazone and BRL 49653 inhibited lipoprotein lipase activity. This inhibition was observed at concentrations as low as 0.1 μM and within 2 h after addition of the drug. Lipoprotein lipase activity was inhibited in differentiated adipocytes as well as the differentiating cells. Despite this decrease in enzyme activity, these drugs increased mRNA levels in …