Shamekh R.,Diabetes and Aging Research Center |
Linden E.H.,Diabetes and Aging Research Center |
Newcomb J.D.,Diabetes and Aging Research Center |
Tigno X.T.,University of South Florida |
And 3 more authors.
Metabolism: Clinical and Experimental | Year: 2011
Nonhuman primates (NHPs) share with humans many features of lipid metabolism and often develop all features of the metabolic syndrome, including hypertriglyceridemia and low high-density lipoprotein cholesterol, and have been used in many studies of potential therapeutics during the preclinical phase. Here we identify for the first time in middle-aged and older rhesus the natural occurrence of hypercholesterolemia, and this hypercholesterolemia develops despite maintenance on a low-cholesterol diet. The aims of this study were to (a) define normal and hypercholesterolemia in rhesus monkeys, (b) determine the factors associated with the development of hypercholesterolemia, (c) compare the lipoprotein profiles in adult rhesus monkeys fed a low-fat/low-cholesterol diet (LFLC) with the profiles of human subjects, and (d) determine the effect of a 16-week high-fat/high-cholesterol (HFHC) diet feeding on total cholesterol and lipoprotein profiles in middle-aged and older monkeys. In our colony, maintained on a constant diet with negligible cholesterol, the mean total cholesterol level in healthy nondiabetic monkeys was 3.7 ± 0.02 mmol/L, with hypercholesterolemia identified as the 95th percentile of the normal cholesterol distribution (>5.2 mmol/L). Severe hypercholesterolemia developed in the HFHC-fed group; however, despite the high-fat diet composition, unexpectedly, no weight gain occurred in these NHPs. The diet-induced hypercholesterolemia differed significantly in lipoprotein pattern from that of the spontaneous hypercholesterolemia. In summary, despite ingesting only a LFLC, NHPs frequently develop hypercholesterolemia, reflecting lipoprotein patterns similar to human subjects; and this lipid profile of spontaneous hypercholesterolemia differs significantly from the hypercholesterolemia induced by an HFHC diet.
Sirjani M.,Shahid Beheshti University of Medical Sciences |
Taleban F.A.,Shahid Beheshti University of Medical Sciences |
Hekmatdoost A.,Shahid Beheshti University of Medical Sciences |
Amiri Z.,Shahid Beheshti University of Medical Sciences |
And 5 more authors.
Iranian Journal of Allergy, Asthma and Immunology | Year: 2014
There has been considerable inconsistency regarding the potential relationship between dyslipidemia and bone metabolism. The inflammatory stimulation through the receptor activator of the nuclear factor kappa-B ligand (RANKL)/ receptor activator of the nuclear factor kappa-B (RANK)/ osteoprotegerin (OPG) pathway could be the infrastructural mechanism for hypercholesterolemia-induced bone loss. In this study, we investigated the effect of dyslipidemia on RANKL and OPG alongside with proinflammatory cytokines. Thirty male C57Bl/6 mice (4 weeks old) were randomized to two purified diet groups (15 animals in each group), high fat, low carbohydrate diet (HFLCD) and its matched low fat, high carbohydrate diet (LFHCD). After 12 weeks of feeding in standard situations, the plasma concentration of lipid profile, interleukin (IL)1Beta, IL-6, tumor necrosis factor-alpha (TNF-4) and RANKL, OPG, and RANKL: OPG ratio were measured. In the present study, although the body weight significantly increased during 12 weeks in HFLCD and LFHCD groups, there were no significant differences in food intake, food efficiency ratio and weight gain between the two groups. The LFHCD group had significantly higher median RANKL and RANKL/OPG ratio. There was no significant difference in plasma IL-16, IL-6 and TNF-4 concentration between LFHCD and HFLCD groups. These unexpected findings from LFHCD, that seem to be as a result of its higher carbohydrate proportion in comparison to HFLCD, implicate dietary carbohydrate rather than dietary fat as a more significant nutritional factor contributing to change in RANKL level and RANKL: OPG ratio. Copyright© Summer 2014, Iran J Allergy Asthma Immunol. All rights reserved.
Chassaing B.,Georgia State University |
Miles-Brown J.,Georgia State University |
Pellizzon M.,Research Diets Inc. |
Ulman E.,Research Diets Inc. |
And 5 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2015
Diet-induced obesity is often modeled by comparing mice fed high-fat diet (HFD), which is made from purified ingredients, vs. normal chow diet (NCD), which is a low-fat assemblage of relatively unrefined plant and animal products. The mechanism by which HFD promotes adiposity is complex but thought to involve low-grade inflammation and altered gut microbiota. The goal of this study was to investigate the extent to which HFD-induced adiposity is driven by fat content vs. other factors that differentiate HFD vs. NCD. Mice were fed NCD, HFD, or other compositionally defined diets (CDD), designed to mimic NCD and/or explore the role of HFD components. A range of metabolic parameters reflecting low-grade inflammation and adiposity were assayed. Relative to NCD, HFD, and to a lesser, but, nonetheless, significant extent, CDD induced increased adiposity, indicating both lipid content and other aspects of HFD are obesogenic. Moreover, HFD and CDD induced a rapid and marked loss of cecal and colonic mass. Such CDD-induced effects were not affected by adjusting dietary protein levels/types but could be largely eliminated by exchanging insoluble fiber (cellulose) for soluble fiber (inulin). Replacing cellulose with inulin in HFD also protected mice against decreased intestinal mass, hyperphagia, and increased adiposity. Such beneficial effects of inulin were microbiota dependent, correlated with elevated fecal short-chain fatty acid levels analyzed via 1H-NMR-based metabolomics and were partially recapitulated by administration of short-chain fatty acid. HFD-induced obesity is strongly promoted by its lack of soluble fiber, which supports microbiota-mediated intestinal tissue homeostasis that prevents inflammation driving obesity and metabolic syndrome. © 2015 the American Physiological Society.
Boyle C.N.,University of Southern California |
Lorenzen S.M.,University of Southern California |
Compton D.,Research Diets Inc. |
Watts A.G.,University of Southern California
Physiology and Behavior | Year: 2012
The anorexia that results from extended periods of cellular dehydration is an important physiological adaptation that limits the intake of osmolytes from food and helps maintain the integrity of fluid compartments. The ability to experimentally control both the development and reversal of anorexia, together with the understanding of underlying hormonal and neuropeptidergic signals, makes dehydration (DE)-anorexia a powerful model for exploring the interactions of neural networks that stimulate and inhibit food intake. However, it is not known which meal parameters are affected by cellular dehydration to generate anorexia. Here we use continuous and high temporal resolution recording of food and fluid intake, together with a drinking-explicit method of meal pattern analysis to explore which meal parameters are modified during DE-anorexia. We find that the most important factor responsible for DE-anorexia is the failure to maintain feeding behavior once a meal has started, rather than the ability to initiate a meal, which remains virtually intact. This outcome is consistent with increased sensitivity to satiation signals and post-prandial satiety mechanisms. We also find that DE-anorexia significantly disrupts the temporal distribution of meals across the day so that the number of nocturnal meals gradually decreases while diurnal meal number increases. Surprisingly, once DE-anorexia is reversed this temporal redistribution is maintained for at least 4. days after normal food intake has resumed, which may allow increased daily food intake even after normal satiety mechanisms are reinstated. Therefore, DE-anorexia apparently develops from a selective targeting of those neural networks that control meal termination, whereas meal initiation mechanisms remain viable. © 2011 Elsevier Inc.
Gajda A.M.,Research Diets Inc. |
Pellizzon M.A.,Research Diets Inc. |
Ricci M.R.,Research Diets Inc.
Methods in Pharmacology and Toxicology | Year: 2012
Animal models of disease are important tools that allow us to model human conditions and test therapies. Metabolic disease, also called the Metabolic Syndrome (MS), is characterized by obesity, insulin resistance (IR), dyslipidemia and hypertension, the simultaneous occurrence of which increases the risk for developing coronary artery disease, type II diabetes and stroke. While genetic (spontaneous) animal models exist, many researchers prefer diet-induced models of the MS, since it is generally thought that the environment (and particularly the diet) plays a large role in the growing incidence of this disease in humans. This chapter will briefly outline some of the diet-induced approaches for animal models of the MS. © 2012 Springer Science+Business Media, LLC.
Nizar J.M.,Stanford University |
Dong W.,Stanford University |
McClellan R.B.,Stanford University |
Labarca M.,Stanford University |
And 9 more authors.
American Journal of Physiology - Renal Physiology | Year: 2016
The majority of patients with obesity, insulin resistance, and metabolic syndrome have hypertension, but the mechanisms of hypertension are poorly understood. In these patients, impaired sodium excretion is critical for the genesis of Na+-sensitive hypertension, and prior studies have proposed a role for the epithelial Na+ channel (ENaC) in this syndrome. We characterized high fat-fed mice as a model in which to study the contribution of ENaC-mediated Na+ reabsorption in obesity and insulin resistance. High fat-fed mice demonstrated impaired Na+ excretion and elevated blood pressure, which was significantly higher on a high-Na+ diet compared with low fat-fed control mice. However, high fat-fed mice had no increase in ENaC activity as measured by Na+ transport across microperfused cortical collecting ducts, electrolyte excretion, or blood pressure. In addition, we found no difference in endogenous urinary aldosterone excretion between groups on a normal or high-Na+ diet. High fat-fed mice provide a model of metabolic syndrome, recapitulating obesity, insulin resistance, impaired natriuresis, and a Na+-sensitive elevation in blood pressure. Surprisingly, in contrast to previous studies, our data demonstrate that high fat feeding of mice impairs natriuresis and produces elevated blood pressure that is independent of ENaC activity and likely caused by increased Na+ reabsorption upstream of the aldosterone-sensitive distal nephron. © 2016 the American Physiological Society.
PubMed | Stanford University, Research Diets Incorporated and Mount Sinai School of Medicine
Type: Journal Article | Journal: American journal of physiology. Renal physiology | Year: 2016
The majority of patients with obesity, insulin resistance, and metabolic syndrome have hypertension, but the mechanisms of hypertension are poorly understood. In these patients, impaired sodium excretion is critical for the genesis of Na(+)-sensitive hypertension, and prior studies have proposed a role for the epithelial Na(+) channel (ENaC) in this syndrome. We characterized high fat-fed mice as a model in which to study the contribution of ENaC-mediated Na(+) reabsorption in obesity and insulin resistance. High fat-fed mice demonstrated impaired Na(+) excretion and elevated blood pressure, which was significantly higher on a high-Na(+) diet compared with low fat-fed control mice. However, high fat-fed mice had no increase in ENaC activity as measured by Na(+) transport across microperfused cortical collecting ducts, electrolyte excretion, or blood pressure. In addition, we found no difference in endogenous urinary aldosterone excretion between groups on a normal or high-Na(+) diet. High fat-fed mice provide a model of metabolic syndrome, recapitulating obesity, insulin resistance, impaired natriuresis, and a Na(+)-sensitive elevation in blood pressure. Surprisingly, in contrast to previous studies, our data demonstrate that high fat feeding of mice impairs natriuresis and produces elevated blood pressure that is independent of ENaC activity and likely caused by increased Na(+) reabsorption upstream of the aldosterone-sensitive distal nephron.