Metabolic Consequences of High-Fat Diet Are Attenuated by Suppression of HIF-1α
Open Access
- 1 October 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (10), e46562
- https://doi.org/10.1371/journal.pone.0046562
Abstract
Obesity is associated with tissue hypoxia and the up-regulation of hypoxia inducible factor 1 alpha (HIF-1α). Prior studies in transgenic mice have shown that HIF-1α plays a role in the metabolic dysfunction associated with obesity. Therefore, we hypothesized that, after the development of diet-induced obesity (DIO), metabolic function could be improved by administration of HIF-1α antisense oligonucleotides (ASO). DIO mice were treated with HIF-1α ASO or with control ASO for 8 weeks and compared with an untreated group. We found that HIF-1α ASO markedly suppressed Hif-1α gene expression in adipose tissue and the liver. HIF-1α ASO administration induced weight loss. Final body weight was 41.6±1.4 g in the HIF-1α ASO group vs 46.7±0.9 g in the control ASO group and 47.9±0.8 g in untreated mice (pvs 12±0.1 and 11.9±0.4 kcal/kg/hr, respectively, pvs 0.75±0.01 and 0.76±0.01, respectively, pvs 239±7.8 mg/dl in the control ASO group and 222±8.2 mg/dl in untreated mice, p<0.01), plasma insulin, hepatic glucose output, and liver fat content. These findings demonstrate that the metabolic consequences of DIO are attenuated by HIF-1α ASO treatment.This publication has 52 references indexed in Scilit:
- Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ systemGenes & Development, 2012
- Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomesJournal of Applied Physiology, 2011
- Adipose Tissue-specific Inhibition of Hypoxia-inducible Factor 1α Induces Obesity and Glucose Intolerance by Impeding Energy Expenditure in Mice*Online Journal of Public Health Informatics, 2010
- Hypoxia-Inducible Factor 1α Induces Fibrosis and Insulin Resistance in White Adipose TissueMolecular and Cellular Biology, 2009
- Biochemical and physiological function of stearoyl-CoA desaturaseAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissueAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- Emerging role of adipose tissue hypoxia in obesity and insulin resistanceInternational Journal of Obesity, 2008
- UCP1: its involvement and utility in obesityInternational Journal of Obesity, 2008
- Analyzing real-time PCR data by the comparative CT methodNature Protocols, 2008
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001