Effects of high-fat diet and AMP-activated protein kinase modulation on the regulation of whole-body lipid metabolism
| Autor: | Milena Schönke, Julie Massart, Juleen R. Zierath |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty QD415-436 Oxidative phosphorylation AMP-Activated Protein Kinases Gene mutation Diet High-Fat Biochemistry Palmitic acid Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Insulin resistance AMP-activated protein kinase Lipid oxidation Internal medicine Methods fatty acids/oxidation medicine Animals Muscle Skeletal biology metabolic kinetics Lipid metabolism Cell Biology Lipid Metabolism medicine.disease Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation chemistry Mutation biology.protein Epoxy Compounds diet effects/lipid metabolism 030217 neurology & neurosurgery Etomoxir |
| Zdroj: | Journal of Lipid Research, Vol 59, Iss 7, Pp 1276-1282 (2018) |
| ISSN: | 0022-2275 |
| Popis: | Metabolic flexibility, the capacity to adapt to fuel availability for energy production, is crucial for maintaining whole-body energy homeostasis. An inability to adequately promote FA utilization is associated with lipid accumulation in peripheral tissues and contributes to the development of insulin resistance. In vivo assays to quantify whole-body lipid oxidation in mouse models of insulin resistance are lacking. We describe a method for assessing whole-body FA oxidation in vivo, as well as tissue-specific lipid uptake in conscious mice. The method relies on intravenous administration of [9,10-(3)H(N)]palmitic acid combined with a non-β-oxidizable palmitate analog, [1-(14)C]2-bromopalmitic acid. Pretreatment with etomoxir, a CPT1 inhibitor that prevents the shuttling of FAs into mitochondria, markedly reduced the appearance of the β-oxidation product (3)H(2)O in circulation and reduced lipid uptake by oxidative tissues including heart and soleus muscle. Whole-body fatty oxidation was unaltered between chow- or high-fat-fed WT and transgenic mice expressing a mutant form of the AMPK γ3 subunit (AMPKγ3(R225Q)) in skeletal muscle. High-fat feeding increased lipid oxidation in WT and AMPKγ3(R225Q) transgenic mice. In conclusion, this technique allows for the assessment of the effect of pharmaceutical agents, as well as gene mutations, on whole-body FA oxidation in mice. |
| Databáze: | OpenAIRE |
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