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Method Of Predicting Obesity Comprising Measuring Neurotensin, B. Mark Evers, Jing Li, Paul Dobner, Olle Melander

Surgery Faculty Patents

The presently disclosed subject matter relates to a method for predicting increased risk of obesity on a non-obese subject. More particularly, the presently disclosed subject matter relates to a method of predicting increased risk of obesity in a non-obese subject by determining a level of neurotensin expression in a biological sample from the subject and comparing the level of neurotensin expression in the sample with a control level. The presently disclosed subject matter further relates to a method of preventing and/or treating obesity in a subject in need thereof by administering to the subject an effective amount of an agent …

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Contributing Factors To Diabetic Brain Injury And Cognitive Decline, Nirmal Verma, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

The link of diabetes with co-occurring disorders in the brain involves complex and multifactorial pathways. Genetically engineered rodents that express familial Alzheimer's disease-associated mutant forms of amyloid precursor protein and presenilin 1 (PSEN1) genes provided invaluable insights into the mechanisms and consequences of amyloid deposition in the brain. Adding diabetes factors (obesity, insulin impairment) to these animal models to predict success in translation to clinic have proven useful at some extent only. Here, we focus on contributing factors to diabetic brain injury with the aim of identifying appropriate animal models that can be used to mechanistically dissect the …

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An Integrative Cross-Omics Analysis Of Dna Methylation Sites Of Glucose And Insulin Homeostasis, Jun Liu, Elena Carnero-Montoro, Jenny Van Dongen, Samantha Lent, Ivana Nedeljkovic, Symen Ligthart, Pei-Chien Tsai, Tiphaine C. Martin, Pooja R. Mandaviya, Rick Jansen, Marjolein J. Peters, Liesbeth Duijts, Vincent W. V. Jaddoe, Henning Tiemeier, Janine F. Felix, Gonneke Willemsen, Eco J. C. De Geus, Audrey Y. Chu, Daniel Levy, Shih-Jen Hwang, Jan Bressler, Rahul Gondalia, Elias L. Salfati, Christian Herder, Bertha A. Hidalgo, Toshiko Tanaka, Ann Zenobia Moore, Rozenn N. Lemaitre, Min A. Jhun, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation …

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Dennd5b Regulates Intestinal Triglyceride Absorption And Body Mass, Scott M. Gordon, Edward B. Neufeld, Zhihong Yang, Milton Pryor, Lita A. Freeman, Xiao Fan, Iftikhar J. Kullo, Leslie G. Biesecker, Alan T. Remaley

Saha Cardiovascular Research Center Faculty Publications

Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b^−/− mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In …

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Sphk2−/− Mice Are Protected From Obesity And Insulin Resistance, Shwetha Ravichandran, Brian S. Finlin, Philip A. Kern, Sabire Özcan

Clinical and Translational Science Faculty Publications

Sphingosine kinases phosphorylate sphingosine to sphingosine 1‑phosphate (S1P), which functions as a signaling molecule. We have previously shown that sphingosine kinase 2 (Sphk2) is important for insulin secretion. To obtain a better understanding of the role of Sphk2 in glucose and lipid metabolism, we have characterized 20- and 52-week old Sphk2^−/− mice using glucose and insulin tolerance tests and by analyzing metabolic gene expression in adipose tissue. A detailed metabolic characterization of these mice revealed that aging Sphk2^−/− mice are protected from metabolic decline and obesity compared to WT mice. Specifically, we found that 52-week old …

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Adipose-Derived Autotaxin Regulates Inflammation And Steatosis Associated With Diet-Induced Obesity, J. Anthony Brandon, Maria Kraemer, Julia Vandra, Suchismita Halder, Margo F. Ubele, Andrew J. Morris, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Autotaxin (ATX) is a secreted enzyme that generates the bioactive lipid lysophosphatidic acid (LPA). We generated mice with global inducible post-natal inactivation or adipose-specific loss of the Enpp2 gene encoding ATX. The animals are phenotypically unremarkable and exhibit differences in adipocyte size and adipose tissue expression of inflammatory genes after high fat feeding without gross differences in fat distribution or body mass. Surprisingly, both models of Enpp2- deficiency exhibited marked protection from high fat diet-induced hepatic steatosis. This phenotype was not associated with differences in dietary fat absorption but may be accounted for by differences in hepatic expression of …

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Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II …

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Full-Text Articles in Entire DC Network

Method Of Predicting Obesity Comprising Measuring Neurotensin, B. Mark Evers, Jing Li, Paul Dobner, Olle Melander

Surgery Faculty Patents

Contributing Factors To Diabetic Brain Injury And Cognitive Decline, Nirmal Verma, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Epidemiology and Environmental Health Faculty Publications

Dennd5b Regulates Intestinal Triglyceride Absorption And Body Mass, Scott M. Gordon, Edward B. Neufeld, Zhihong Yang, Milton Pryor, Lita A. Freeman, Xiao Fan, Iftikhar J. Kullo, Leslie G. Biesecker, Alan T. Remaley

Saha Cardiovascular Research Center Faculty Publications

Sphk2−/− Mice Are Protected From Obesity And Insulin Resistance, Shwetha Ravichandran, Brian S. Finlin, Philip A. Kern, Sabire Özcan

Clinical and Translational Science Faculty Publications

Adipose-Derived Autotaxin Regulates Inflammation And Steatosis Associated With Diet-Induced Obesity, J. Anthony Brandon, Maria Kraemer, Julia Vandra, Suchismita Halder, Margo F. Ubele, Andrew J. Morris, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Chemistry Faculty Publications