Enhanced lipid oxidation rate -
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Download references. We wish to thank Takeda Pharmaceuticals for their financial support and intellectual input in study design. We would also like to thank Hui Xie for his assistance with the statistical analysis of data presented in this study.
This study was made possible through the efforts and dedication of TRI-MD staff and the study volunteers. We wish to extend our gratitude all that participated in this study. This research was funded through a partnership with Takeda Pharmaceuticals.
The Southeast Center for Integrated Metabolomics NIH Grant U24 DKA1 provided support regarding generation of βOHB data included in this study. SP and SS are the guarantors of this work and, such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
SP wrote the manuscript, elaborated tables and figures, participated in the analysis and interpretation of data. FY participated in data analysis. All authors read and approved the final manuscript. SRS and SP received research support from Takeda Pharmaceuticals, Inc.
The other authors have no conflicts of interest. None of the funding sources played a role in the collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication.
The Institutional Review Board at Florida Hospital approved this research for ethical standards, scientific merit, and regulatory compliance IRBNet — The Office of Research Administration ORA provided support and oversight to ensure integrity of this research at Florida Hospital.
Translational Research Institute for Metabolism and Diabetes, Florida Hospital, E. Princeton Street, Orlando, FL, , USA. Stephanie A. Parsons, Karen P. Jones, Fanchao Yi, Christopher P. Metabolomics Core, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, , USA.
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Correspondence to Stephanie A. Pre- and Post-Intralipid Respiratory Quotient Values. RQ measured under fasting conditions, with CHO Diet or without Ad Lib Diet high carbohydrate dietary intake, ±Glucose, and following Intralipid infusion. DOCX kb. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.
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Download PDF. Protocol Open access Published: 06 October A novel clinical approach to evaluating changes in fat oxidation in healthy, overnight-fasted subjects Stephanie A. Parsons 1 , Karen P. Jones 1 , Fanchao Yi 1 , Christopher P.
Bock 1 , Christopher J. Petucci 2 , Stella K. Betancourt 2 , Stephen J. Smith 1 , 2 Show authors Translational Medicine Communications volume 1 , Article number: 6 Cite this article Accesses 1 Altmetric Metrics details.
Abstract Background Obesity is characterized by impaired fat oxidation, and, therefore, the development of therapeutics designed to enhance fat oxidation for treating obesity is a growing focus in drug discovery. Background There is an ever growing need for new and innovative approaches for the treatment of obesity, and obesity-related diseases such as type 2 diabetes.
Methods Ethical approval and screening The study protocol was approved by the Florida Hospital Institutional Review Board and was carried out in accordance with the Declaration of Helsinki.
Subjects Twenty-four healthy men and women between the ages of 19 and 54 years of age took part in this study. Experimental protocol During a baseline visit occurring within two weeks prior to the overnight test visit, a frequently-sampled intravenous glucose tolerance test FSIGTT was performed following an overnight fast.
Full size image. Results The Lean, Saline LS study population was comprised of five lean or overweight males and three lean or overweight females, Lean, Glucose LG group of six lean or overweight males and two lean or overweight females, and the Obese, Saline OS group of four obese males and four obese females.
Table 1 Anthropometric and baseline laboratory values of the study population at screening Full size table. Discussion Increased de novo lipogenesis and impaired fatty acid oxidation appear to be key in the development of obesity and insulin resistance.
Conclusion The pursuit of new anti-obesity pharmacotherapies is increasingly focused on strategies to target pathways important for the regulation of energy balance.
Abbreviations Beta hCG: Beta human chorionic gonadotropin BMI: Body mass index CBC: Complete blood count CHO: Carbohydrate CK: Creatinine kinase CMP: Comprehensive metabolic profile CRP: C reactive protein DBP: Diastolic blood pressure ECG: Electrocardiogram EE: Energy expenditure FAOx: Fatty acid oxidation FSIGTT: Frequently-sampled intravenous glucose tolerance test HDL: High density lipoprotein HR: Heart rate IV: Intravenous LDL: Low density lipoprotein LG: Lean, glucose LS: Lean, saline OS: Obese, saline RQ: Respiratory quotient SBP: Systolic blood pressure TSH: Thyroid-stimulating hormone VCO 2 : CO 2 production VO 2 : O 2 consumption βOHB: β-hydroxybutyrate.
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Hence, an understanding of the factors that increase or decrease fat oxidation is important. Exercise intensity and duration are important determinants of fat oxidation.
Fat oxidation rates increase from low to moderate intensities and then decrease when the intensity becomes high. HFD Results in Rapid Increase in Lipid Metabolism In an effort to understand the progression of changes in lipid oxidation in response to HFD consumption, we quantified the initial whole body metabolic response using the comprehensive laboratory animal monitoring system CLAMS.
Skeletal Muscle is not Insulin Resistant Following 3 Weeks of HFD Despite Glucose Intolerance Following either an overnight or a 6 hour fast an intraperitoneal glucose tolerance test IPGTT was performed.
Figure 3. Indices of glucose intolerance and muscle insulin resistance following 3 weeks of HFD. Increased Inflammation in Adipose Tissue, but Little to no Change in Liver, Muscle or Blood Following 3 Weeks of HFD Lipid overload and inflammation in adipose tissue and liver is linked to the onset of insulin resistance in these organs [16] , [17] , [27] , [28].
Figure 4. Indices of adipose, liver, blood and muscle inflammation following 3 weeks of HFD. Figure 5. Pro-inflammatory transcripts in muscle following 8 weeks of HFD. Discussion Our results indicate that the early, whole body response to HFD, particularly that of skeletal muscle, is a protective adaptation which provides a buffering period of time before the onset of insulin resistance in muscle after 8 weeks of HFD as previously demonstrated in this model [18].
Methods Animals and Blood Sampling All experimental protocols were approved by the McMaster University Animal Care Committee in accordance with the Canadian Council for Animal Care guidelines. Experimental Procedures Group 1 mice were weighed then euthanized by cervical dislocation following 3 or 8 weeks of diet and tissues were harvested and either snap frozen or mounted with tissue freezing medium and frozen in isopentane cooled by liquid nitrogen then frozen in liquid nitrogen.
Histochemical Analysis Serial sections of GP muscle 8 µm were cut on a cryostat with one section used for a metachromatic stain to determine fiber type and the other section used for a IIA myosin immunofluorescent IF and Oil-Red-O co-stain to confirm fiber type and assess IMCL deposition.
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Research Oxdation Immunology Metabolism Open Access Address Enhanced lipid oxidation rate to: Qing Yi, Fannin Street, SM, Houston, TexasUSA. Phone: Find articles by Xiao, L. in: JCI PubMed Google Scholar.
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