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
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