Basal lipolysis, not the degree of insulin resistance, differentiates large from small isolated adipocytes in high-fat fed mice
Autor: | Stephan Wueest, Julia M. Rytka, Daniel Konrad, E. J. Schoenle, Reto A. Rapold |
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Přispěvatelé: | University of Zurich, Konrad, D |
Rok vydání: | 2009 |
Předmět: |
Male
medicine.medical_specialty Cell Survival Endocrinology Diabetes and Metabolism medicine.medical_treatment Lipolysis Adipose tissue 030209 endocrinology & metabolism 610 Medicine & health Cell Separation Biology Carbohydrate metabolism 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Insulin resistance Internal medicine Adipocyte Internal Medicine medicine Adipocytes Animals Insulin RNA Messenger Pancreatic hormone 030304 developmental biology Cell Size 0303 health sciences Glucose tolerance test medicine.diagnostic_test Lipase Glucose Tolerance Test medicine.disease Dietary Fats Mice Inbred C57BL 2712 Endocrinology Diabetes and Metabolism Endocrinology Glucose chemistry 10036 Medical Clinic 2724 Internal Medicine 10076 Center for Integrative Human Physiology 570 Life sciences biology Insulin Resistance Carboxylic Ester Hydrolases |
Zdroj: | Diabetologia |
DOI: | 10.5167/uzh-12239 |
Popis: | AIMS/HYPOTHESIS Adipocytes in obesity are characterised by increased cell size and insulin resistance compared with adipocytes isolated from lean patients. However it is not clear at present whether hypertrophy actually does drive adipocyte insulin resistance. Thus the aim of the present study was to metabolically characterise small and large adipocytes isolated from epididymal fat pads of mice fed a high fat diet (HFD). METHODS C57BL/6J mice were fed normal chow or HFD for 8 weeks. Adipocytes from epididymal fat pads were isolated by collagenase digestion and in HFD fed mice separated into two fractions according to their size by filtration through a nylon mesh. Viability was assessed by lactate dehydrogenase and 3 (45 dimethylthiazol 2 yl) 2 5 diphenyltetrazolium assays. Basal and insulin stimulated D [U (14)C]glucose incorporation and lipolysis were measured. Protein levels and mRNA expression were determined by western blot and real time RT PCR respectively. RESULTS Insulin stimulated D [U (14)C]glucose incorporation into adipocytes isolated from HFD fed mice was reduced by 50 compared with adipocytes from chow fed mice. However it was similar between small (average diameter 60.9 +/ 3.1 microm) and large (average diameter 83.0 +/ 6.6 microm) adipocytes. Similarly insulin stimulated phosphorylation of protein kinase B and AS160 were reduced to the same extent in small and large adipocytes isolated from HFD mice. In addition insulin failed to inhibit lipolysis in both adipocyte fractions whereas it decreased lipolysis by 30 in adipocytes of chow fed mice. In contrast large and small adipocytes differed in basal lipolysis rate which was twofold higher in the larger cells. The latter finding was associated with higher mRNA expression levels of Atgl (also known as Pnpla2) and Hsl (also known as Lipe) in larger adipocytes. Viability was not different between small and large adipocytes. CONCLUSIONS/INTERPRETATION Rate of basal lipolysis but not insulin responsiveness is different between small and large adipocytes isolated from epididymal fat pads of HFD fed mice. |
Databáze: | OpenAIRE |
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