Open Access. Powered by Scholars. Published by Universities.®
Translational Medical Research Commons™
Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 8 of 8
Full-Text Articles in Translational Medical Research
Human Body Composition And Immunity: Visceral Adipose Tissue Produces Il-15 And Muscle Strength Inversely Correlates With Nk Cell Function In Elderly Humans, Ahmad Al-Attar, Steven R. Presnell, Jody L. Clasey, Douglas E. Long, R. Grace Walton, Morgan Sexton, Marlene E. Starr, Philip A. Kern, Charlotte A. Peterson, Charles T. Lutz
Human Body Composition And Immunity: Visceral Adipose Tissue Produces Il-15 And Muscle Strength Inversely Correlates With Nk Cell Function In Elderly Humans, Ahmad Al-Attar, Steven R. Presnell, Jody L. Clasey, Douglas E. Long, R. Grace Walton, Morgan Sexton, Marlene E. Starr, Philip A. Kern, Charlotte A. Peterson, Charles T. Lutz
Clinical and Translational Science Faculty Publications
Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections and cancers, but these crucial activities decline with age. NK cell development, homeostasis, and function require IL-15 and its chaperone, IL-15 receptor alpha (IL-15Rα). Macrophages and dendritic cells (DC) are major sources of these proteins. We had previously postulated that additional IL-15 and IL-15Rα is made by skeletal muscle and adipose tissue. These sources may be important in aging, when IL-15-producing immune cells decline. NK cells circulate through adipose tissue, where they may be exposed to local IL-15. The objectives of this work were to determine (1) if human muscle, …
Pioglitazone Induces Apoptosis Of Macrophages In Human Adipose Tissue, Angela M. Bodles, Vijayalakshmi Varma, Aiwei Yao-Borengasser, Bounleut Phanavanh, Charlotte A. Peterson, Robert E. Mcgehee Jr., Neda Rasouli, Martin Wabitsch, Philip A. Kern
Pioglitazone Induces Apoptosis Of Macrophages In Human Adipose Tissue, Angela M. Bodles, Vijayalakshmi Varma, Aiwei Yao-Borengasser, Bounleut Phanavanh, Charlotte A. Peterson, Robert E. Mcgehee Jr., Neda Rasouli, Martin Wabitsch, Philip A. Kern
Clinical and Translational Science Faculty Publications
Metabolic syndrome and type 2 diabetes mellitus are associated with an increased number of macrophage cells that infiltrate white adipose tissue (WAT). Previously, we demonstrated that the treatment of subjects with impaired glucose tolerance (IGT) with the peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone resulted in a decrease in macrophage number in adipose tissue. Here, adipose tissue samples from IGT subjects treated with pioglitazone were examined for apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. TUNEL-positive cells were identified, and there was a significant 42% increase in TUNEL-positive cells following pioglitazone treatment. Overlay experiments with anti-CD68 antibody …
Transgenic Mice Expressing Lipoprotein Lipase In Adipose Tissue: Absence Of The Proximal 3′-Untranslated Region Causes Translational Upregulation, Lori L. Hensley, Gouri Ranganathan, Elke M. Wagner, Brian D. Wells, Joseph C. Daniel, Diane Vu, Clay F. Semenkovich, Rudolf Zechner, Philip A. Kern
Transgenic Mice Expressing Lipoprotein Lipase In Adipose Tissue: Absence Of The Proximal 3′-Untranslated Region Causes Translational Upregulation, Lori L. Hensley, Gouri Ranganathan, Elke M. Wagner, Brian D. Wells, Joseph C. Daniel, Diane Vu, Clay F. Semenkovich, Rudolf Zechner, Philip A. Kern
Clinical and Translational Science Faculty Publications
Lipoprotein lipase (LPL) is a key enzyme in lipoprotein and adipocyte metabolism. Defects in LPL can lead to hypertriglyceridemia and the subsequent development of atherosclerosis. The mechanisms of regulation of this enzyme are complex and may occur at multiple levels of gene expression. Because the 3′-untranslated region (UTR) is involved in LPL translational regulation, transgenic mice were generated with adipose tissue expression of an LPL construct either with or without the proximal 3′-UTR and driven by the aP2 promoter. Both transgenic mouse colonies were viable and expressed the transgene, resulting in a 2-fold increase in LPL activity in white adipose …
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
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 (SI) (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 SI, subjects who were discordant for SI were matched for BMI, age, and sex. Using this approach, insulin-sensitive subjects demonstrated a twofold higher plasma level of …
The Translational Regulation Of Lipoprotein Lipase In Diabetic Rats Involves The 3′-Untranslated Region Of The Lipoprotein Lipase Mrna, Gouri Ranganathan, Chunling Li, Philip A. Kern
The Translational Regulation Of Lipoprotein Lipase In Diabetic Rats Involves The 3′-Untranslated Region Of The Lipoprotein Lipase Mrna, Gouri Ranganathan, Chunling Li, Philip A. Kern
Clinical and Translational Science Faculty Publications
Adipose tissue lipoprotein lipase (LPL) activity is decreased in patients with poorly controlled diabetes, and this contributes to the dyslipidemia of diabetes. To study the mechanism of this decrease in LPL, we studied adipose tissue LPL expression in male rats with streptozotocin-induced diabetes. Heparin releasable and extractable LPL activity in the epididymal fat decreased by 75-80% in the diabetic group and treatment of the rats with insulin prior to sacrifice reversed this effect. Northern blot analysis indicated no corresponding change in LPL mRNA levels. However, LPL synthetic rate, measured using [35S]methionine pulse labeling, was decreased by 75% in …
Role Of Protein Kinase C In The Translational Regulation Of Lipoprotein Lipase In Adipocytes, Gouri Ranganathan, Rami Kaakaji, Philip A. Kern
Role Of Protein Kinase C In The Translational Regulation Of Lipoprotein Lipase In Adipocytes, Gouri Ranganathan, Rami Kaakaji, Philip A. Kern
Clinical and Translational Science Faculty Publications
The hypertriglyceridemia of diabetes is accompanied by decreased lipoprotein lipase (LPL) activity in adipocytes. Although the mechanism for decreased LPL is not known, elevated glucose is known to increase diacylglycerol, which activates protein kinase C (PKC). To determine whether PKC is involved in the regulation of LPL, we studied the effect of 12-O-tetradecanoyl phorbol 13-acetate (TPA) on adipocytes. LPL activity was inhibited when TPA was added to cultures of 3T3-F442A and rat primary adipocytes. The inhibitory effect of TPA on LPL activity was observed after 6 h of treatment, and was observed at a concentration of 6 nM. …
Thiazolidinediones Inhibit Lipoprotein Lipase Activity In Adipocytes, Subramanian Ranganathan, Philip A. Kern
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 …
Tissue-Specific Expression Of Human Lipoprotein Lipase: Effect Of The 3′-Untranslated Region On Translation, Gouri Ranganathan, John M. Ong, Ada Yukht, Mehrnoosh Saghizadeh, Rosa B. Simsolo, Andrea Pauer, Philip A. Kern
Tissue-Specific Expression Of Human Lipoprotein Lipase: Effect Of The 3′-Untranslated Region On Translation, Gouri Ranganathan, John M. Ong, Ada Yukht, Mehrnoosh Saghizadeh, Rosa B. Simsolo, Andrea Pauer, Philip A. Kern
Clinical and Translational Science Faculty Publications
Lipoprotein lipase (LPL) is a central enzyme in lipoprotein metabolism and is expressed predominantly in adipose tissue and muscle. In these tissues, the regulation of LPL is complex and often opposite in response to the same physiologic stimulus. In addition, much regulation of LPL occurs post-transcriptionally. The human LPL cDNA is characterized by a long 3′-untranslated region, which has two polyadenylation signals. In this report, human adipose tissue expressed two LPL mRNA species (3.2 and 3.6 kb) due to an apparent random choice of sites for mRNA polyadenylation, whereas human skeletal and heart muscle expressed predominantly the longer 3.6-kb mRNA …