Life Sciences Commons^™

Vitamin A And Feeding Statuses Modulate The Insulin-Regulated Gene Expression In Zucker Lean And Fatty Primary Rat Hepatocytes, Wei Chen, Meredith L. Howell, Yang Li, Rui Li, Guoxun Chen

Nutrition Publications and Other Works

Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications. The mechanism of hepatic insulin resistance at the gene expression level remains unrevealed. To examine the effects of vitamin A (VA), total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL) and fatty (ZF) rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA). We report that the insulin- and RA-regulated glucokinase, sterol regulatory element-binding protein-1c and cytosolic form of phosphoenolpyruvate carboxykinase expressions are impaired …

The Interaction Of Botanicals And Ampk Signaling In The Inhibition Of Castrate-Resistant Prostate Cancer, Jay Whelan, Yi Zhao

Nutrition Publications and Other Works

Reprogramming of metabolic pathways and abnormal acetylation of DNA are two common features of cancer, including prostate cancer (PCa).

Zyflamend, A Polyherbal Mixture, Down Regulates Class I And Class Ii Histone Deacetylases And Increases P21 Levels In Castrate-Resistant Prostate Cancer Cells, E-Chu Huang, Yi Zhao, Guoxun Chen, Seung Joon Baek, Michael F. Mcentee, Steven Minkin, John P. Biggerstaff, Jay Whelan

Nutrition Publications and Other Works

Background

Zyflamend, a mixture containing extracts of ten herbs, has shown promise in a variety of preclinical cancer models, including prostate cancer. The current experiments were designed to investigate the effects of Zyflamend on the expression of class I and II histone deacetylases, a family of enzymes known to be over expressed in a variety of cancers.

Methods

CWR22Rv1 cells, a castrate-resistant prostate cancer cell line, were treated with Zyflamend and the expression of class I and II histone deacetylases, along with their downstream target the tumor suppressor gene p21, was investigated. Involvement of p21 was confirmed with siRNA knockdown …

Pancreatic Β-Cell Death In Response To Pro-Inflammatory Cytokines Is Distinct From Genuine Apoptosis, J. Jason Collier, Susan J. Burke, Mary E. Eisenhauer, Danhong Lu, Renee C. Sapp, Carlie J. Frydman, Shawn R. Campagna

Nutrition Publications and Other Works

A reduction in functional β-cell mass leads to both major forms of diabetes; pro-inflammatory cytokines, such as interleukin-1beta (IL-1β) and gamma-interferon (γ-IFN), activate signaling pathways that direct pancreatic β-cell death and dysfunction. However, the molecular mechanism of β-cell death in this context is not well understood. In this report, we tested the hypothesis that individual cellular death pathways display characteristic phenotypes that allow them to be distinguished by the precise biochemical and metabolic responses that occur during stimulus-specific initiation. Using 832/13 and INS-1E rat insulinoma cells and isolated rat islets, we provide evidence that apoptosis is unlikely to be the …

The Influence Of Commercially-Available Carbohydrate And Carbohydrate-Protein Supplements On Endurance Running Performance In Recreational Athletes During A Field Trial, Adriana Coletta, Dixie L. Thompson, Holly A. Raynor

Nutrition Publications and Other Works

Background

It is recommended that endurance athletes consume carbohydrate (CHO) supplements, providing 6-8% CHO concentration, during exercise > 60 minutes to improve athletic performance. Recently research has compared carbohydrate-protein (CHO-P) supplementation to the traditionally used CHO supplementation during endurance exercise, following these supplementation recommendations, in controlled settings, but not under simulated applied conditions such as a field trial. Therefore, the purpose of the present investigation was to test CHO and CHO-P supplementation under applied conditions such that commercially-available isocaloric (CHO-P & double-carbohydrate [CHO-CHO]) and isocarbohydrate (CHO-P & CHO) supplements were compared to a placebo (PLA), within an outdoor running field trial …

Synergistic Effects Of Leucine And Resveratrol On Insulin Sensitivity And Fat Metabolism In Adipocytes And Mice, Antje Bruckbauer, Michael B. Zemel, Teresa Thorpe, Murthy R. Akula, Alan C. Stuckey, Dustin Ryan Osborne, Emily B. Martin, Stephen Kennel, Jonathan S. Wall

Nutrition Publications and Other Works

Background

Sirtuins are important regulators of glucose and fat metabolism, and sirtuin activation has been proposed as a therapeutic target for insulin resistance and diabetes. We have shown leucine to increase mitochondrial biogenesis and fat oxidation via Sirt1 dependent pathways. Resveratrol is a widely recognized activator of Sirt; however, the biologically-effective high concentrations used in cell and animal studies are generally impractical or difficult to achieve in humans. Accordingly, we sought to determine whether leucine would exhibit synergy with low levels of resveratrol on sirtuin-dependent outcomes in adipocytes and in diet-induced obese (DIO) mice.

Methods

3T3-L1 mouse adipocytes were treated …

Effects Of Dairy Consumption On Sirt1 And Mitochondrial Biogenesis In Adipocytes And Muscle Cells, Antje Bruckbauer, Michael B. Zemel

Nutrition Publications and Other Works

Background

Recent data from this laboratory suggest that components of dairy foods may serve as activators of SIRT1 (Silent Information Regulator Transcript 1), and thereby participate in regulation of glucose and lipid metabolism. In this study, an ex-vivo/in-vitro approach was used to examine the integrated effects of dairy diets on SIRT1 activation in two key target tissues (adipose and muscle tissue).

Methods

Serum from overweight and obese subjects fed low or high dairy diets for 28 days was added to culture medium (similar to conditioned media) to treat cultured adipocytes and muscle cells for 48 hours.

Results

Treatment with high …

Dietary Fat And Not Calcium Supplementation Or Dairy Product Consumption Is Associated With Changes In Anthropometrics During A Randomized, Placebo-Controlled Energy-Restriction Trial, Jennifer T. Smilowitz, Michelle M. Wiest, Dorothy Teegarden, Michael B. Zemel, Bruce J. German, Marta D. Van Loan

Nutrition Publications and Other Works

Insufficient calcium intake has been proposed to cause unbalanced energy partitioning leading to obesity. However, weight loss interventions including dietary calcium or dairy product consumption have not reported changes in lipid metabolism measured by the plasma lipidome.

Methods

The objective of this study was to determine the relationships between dairy product or supplemental calcium intake with changes in the plasma lipidome and body composition during energy restriction. A secondary objective of this study was to explore the relationships among calculated macronutrient composition of the energy restricted diet to changes in the plasma lipidome, and body composition during energy restriction. Overweight …

Allometric Scaling Of Dietary Linoleic Acid On Changes In Tissue Arachidonic Acid Using Human Equivalent Diets In Mice, Kylie A. Weldon, Jay Whelan

Nutrition Publications and Other Works

Background

It is hypothesized that dietary linoleic acid (LA) promotes chronic and acute diseases in humans by enriching tissues with arachidonic acid (AA), its downstream metabolite, and dietary studies with rodents have been useful for validation. However, levels of LA in research diets of rodents, as published in the literature, are notoriously erratic making interspecies comparisons unreliable. Therefore, the ability to extrapolate the biological effects of dietary LA from experimental rodents to humans necessitates an allometric scaling model that is rooted within a human equivalent context.

Methods

To determine the physiological response of dietary LA on tissue AA, a mathematical …

Increasing Dietary Linoleic Acid Does Not Increase Tissue Arachidonic Acid Content In Adults Consuming Western-Type Diets: A Systematic Review, Jay Whelan, Brian Rett

Nutrition Publications and Other Works

Background

Linoleic acid, with a DRI of 12-17 g/d, is the most highly consumed polyunsaturated fatty acid in the Western diet and is found in virtually all commonly consumed foods. The concern with dietary linoleic acid, being the metabolic precursor of arachidonic acid, is its consumption may enrich tissues with arachidonic acid and contribute to chronic and overproduction of bioactive eicosanoids. However, no systematic review of human trials regarding linoleic acid consumption and subsequent changes in tissue levels of arachidonic acid has been undertaken.

Objective

In this study, we reviewed the human literature that reported changes in dietary linoleic acid …

Genetic And Genomic Analysis Of Hyperlipidemia, Obesity And Diabetes Using (C57bl/6j × Tallyho/Jngj) F2 Mice, Taryn P. Stewart, Hyoung Y. Kim, Arnold M. Saxton, Jung H. Kim

Nutrition Publications and Other Works

Background

Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The genetic contribution to human T2D and related metabolic disorders is evident, and mostly follows polygenic inheritance. The TALLYHO/JngJ (TH) mice are a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia.

Results

In order to determine the genetic factors that contribute to these T2D related characteristics in TH mice, we interbred TH mice with C57BL/6J (B6) mice. The parental, F1, and …

Leucine Modulation Of Mitochondrial Mass And Oxygen Consumption In Skeletal Muscle Cells And Adipocytes, Xiaocun Sun, Michael B. Zemel

Nutrition Publications and Other Works

Background

The effects of dairy on energy metabolism appear to be mediated, in part, by leucine and calcium which regulate both adipocyte and skeletal muscle energy metabolism. We recently demonstrated that leucine and calcitriol regulate fatty acid oxidation in skeletal muscle cells in vitro, with leucine promoting and calcitriol suppressing fatty acid oxidation. Moreover, leucine coordinately regulated adipocyte lipid metabolism to promote flux of lipid to skeletal muscle and regulate metabolic flexibility. We have now investigated the role of mitochondrial biogenesis in mediating these effects.

Methods

We tested the effect of leucine, calcitriol and calcium in regulation of mitochondrial …

Retinoids Synergize With Insulin To Induce Hepatic Gck Expression., Guoxun Chen

Nutrition Publications and Other Works

Hepatic GK (glucokinase) plays a key role in maintaining glucose homoeostasis. Many stimuli regulate GK activity by controlling its gene transcription. We hypothesized that endogenous lipophilic molecules modulate hepatic Gck expression. Lipophilic molecules were extracted from rat livers, saponified and re-constituted as an LE (lipophilic extract). LE synergized with insulin to induce primary hepatocyte, but not beta-cell, Gck expression in an SREBP-1c (sterol-regulatory-element-binding protein-1c)-independent manner. The dramatic induction of Gck mRNA resulted in a significant increase in GK activity. Subsequently, the active molecules were identified as retinol and retinal by MS after the purification of the active LE fractions. Retinoids …

N3 And N6 Polyunsaturated Fatty Acids Differentially Modulate Prostaglandin E Secretion But Not Markers Of Lipogenesis In Adipocytes, Patrick Wortman, Yuko Miyazaki, Nishan Sudheera Kalupahana, Suyeon Kim, Melissa Hansen-Petrik, Arnold M. Saxton, Kate J. Claycombe, Brynn H. Voy, Jay Whelan, Naima Moustaid-Moussa

Nutrition Publications and Other Works

A dramatic rise in the incidence of obesity in the U.S. has accelerated the search for interventions that may impact this epidemic. One recently recognized target for such intervention is adipose tissue, which secretes a variety of bioactive substances including prostaglandins. Prostaglandin E₂ (PGE₂) has been shown to decrease lipolysis in adipocytes, but limited studies have explored alternative mechanisms by which PGE₂ might impact obesity, such as adipogenesis or lipogenesis. Studies conducted on Apc^Min/+ mice indicated that selective inhibition of the cyclooxygenase (COX)-2 enzyme led to significant reductions in fatty acid synthase (FAS) activity in …

Effects Of Dairy Intake On Weight Maintenance, Michael B. Zemel, Joseph E. Donnelly, Bryan K. Smith, Debra K. Sullivan, Joanna Richards, Danielle Morgan-Hanusa, Matthew S. Mayo, Xiaocun Sun, Galen Cook-Wiens, Bruce W. Bailey, Emily L. Van Walleghen, Richard A. Washburn

Nutrition Publications and Other Works

Background

To compare the effects of low versus recommended levels of dairy intake on weight maintenance and body composition subsequent to weight loss.

Design and Methods

Two site (University of Kansas-KU; University of Tennessee-UT), 9 month, randomized trial. Weight loss was baseline to 3 months, weight maintenance was 4 to 9 months. Participants were maintained randomly assigned to low dairy (< 1 dairy serving/d) or recommended dairy (> 3 servings/d) diets for the maintenance phase. Three hundred thirty eight men and women, age: 40.3 ± 7.0 years and BMI: 34.5 ± 3.1, were randomized; Change in weight and body composition (total fat, trunk fat) from 4 to …

Home Grocery Delivery Improves The Household Food Environments Of Behavioral Weight Loss Participants: Results Of An 8-Week Pilot Study, Amy A. Gorin, Hollie A. Raynor, Heather M. Niemeier, Rena R. Wing

Nutrition Publications and Other Works

Background

Household food availability is consistently linked to dietary intake; yet behavioral weight control treatment includes only minimal instruction on how to change the home environment to support dietary goals. This pilot study examined whether it is feasible to change the household food environments of behavioral weight loss participants through the use of a commercially available grocery home delivery service.

Methods

Overweight participants (N = 28; BMI = 31.7 ± 3.6 kg/m²; 89.3% women, 47.9 ± 9.5 years) were randomly assigned to 8-weeks of standard behavioral weight loss (SBT) or to SBT plus home food delivery (SBT+Home). SBT+Home …

Liver Lipid Molecules Induce Pepck-C Gene Transcription And Attenuate Insulin Action., Guoxun Chen

Nutrition Publications and Other Works

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) plays key roles in gluconeogenesis, glyceroneogenesis, and cataplerosis. Experiments were designed to examine the effects of endogenous lipid molecules from rat livers on the expression of PEPCK-C gene in primary rat hepatocytes. The lipid extracts prepared from livers of Zucker fatty, lean, and Wistar rats induced the expression levels of PEPCK-C transcripts. Insulin-mediated reduction of PEPCK-C gene expression was attenuated by the same treatment. The lipid extracts induced the relative luciferase activity of reporter gene constructs that contain a 2.2-kb 5' promoter fragment of PEPCK-C gene, but not the construct that contains only the 3' untranslated …

Enzymatic Reduction Of Oxysterols Impairs Lxr Signaling In Cultured Cells And The Livers Of Mice., Guoxun Chen

Nutrition Publications and Other Works

Liver X receptors (LXRs) are nuclear receptors that play crucial roles in lipid metabolism in vivo and are activated by oxysterol ligands in vitro. The identity of the ligand that activates LXRs in vivo is uncertain. Here we provide two lines of evidence that oxysterols are LXR ligands in vitro and in vivo. First, overexpression of an oxysterol catabolic enzyme, cholesterol sulfotransferase, inactivates LXR signaling in several cultured mammalian cell lines but does not alter receptor response to the nonsterol agonist T0901317. Adenovirus-mediated expression of the enzyme in mice prevents dietary induction of hepatic LXR target genes by cholesterol but …

Central Role For Liver X Receptor In Insulin-Mediated Activation Of Srebp-1c Transcription And Stimulation Of Fatty Acid Synthesis In Liver., Guoxun Chen

Nutrition Publications and Other Works

Transcription of the gene encoding sterol regulatory element-binding protein 1c (SREBP-1c) is known to be activated by insulin in the liver. The resultant SREBP-1c protein activates transcription of the genes required for fatty acid synthesis. Here, we use SREBP-1c promoter reporter constructs to dissect the mechanism of insulin activation in freshly isolated rat hepatocytes. The data show that a complete insulin response (increase of 6- to 11-fold) requires two binding sites for liver X receptors (LXRs), which are nuclear receptors that are activated by oxygenated sterols. Disruption of these binding sites did not lower basal transcription but severely reduced the …

Resistance To Adenovirally Induced Hyperleptinemia In Rats, Guoxun Chen, Kazunori Koyama, Michio Shimabukuro, May-Yun Wang, Young Lee, Pushpa S. Kalra, Michael J. Dube, Satya P. Kalra, Christopher B. Newgard, Roger H. Unger

Nutrition Publications and Other Works

Leptin regulates appetite and body weight via hypothalamic targets, but it can act directly on cultured pancreatic islets to regulate their fat metabolism. To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, shamlesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. Infusion with recombinant adenovirus containing the rat leptin cDNA increased plasma leptin by z 20 ng/ml in VMHL and ZDF rats but had no effect …

Resistance To Adenovirally Induced Hyperleptinemia In Rats, Guoxun Chen, Kazunori Koyama, Michio Shimabukuro, May-Yun Wang, Young Lee, Pushpa S. Kalra, Michael J. Dube, Satya P. Kalra, Christopher B. Newgard, Roger H. Unger

Nutrition Publications and Other Works

Leptin regulates appetite and body weight via hypothalamic targets, but it can act directly on cultured pancreatic islets to regulate their fat metabolism. To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, shamlesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. Infusion with recombinant adenovirus containing the rat leptin cDNA increased plasma leptin by z 20 ng/ml in VMHL and ZDF rats but had no effect …

Food Distribution And Consumption In Knoxville: Exploring Food-Related Local Planning Issues, Robert C. Blakey, Edward H. Cole, Katherine Haygood, Stephen L. Hebert, Patrick Bruce King, Myles T. Mcgrane, Jeffrey W. Trombly, Marlon I. Williams, Frederick D. Luce, Robert L. Wilson

Nutrition Publications and Other Works

Summary:

City planners have traditionally made an effort to understand the interrelationships between urban activities and various support systems, such as transportation, water and sewer, waste management, communications and energy. Food is also an important urban support system with a complex system of supply, distribution, and consumption. An understanding of the nature of the food supply and distribution system seems important, but in the past has not been an area of concern for the planning profession. It was the intent of this project to develop a basis from which to seek an understanding of the Knoxville food support system and …