Pecinova 2015 Abstract MiP2015

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Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue.

Link:

Pravenec M, Pecinova A, Mlejnek P, Zidek V, Landa V, Simakova M, Silhavy J, Strnad H, Eigner S, Eigner HK, Skop V, Malinska H, Kazdova L, Drahota Z, Mracek T, Houstek J (2015)

Event: MiP2015

Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin (Retn) transgene specifically in adipose tissue (SHR-Retn), we observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances by its ability to dissipate energy excess.

In the current study, we analyzed autocrine effects of transgenic resistin on BAT glucose and lipid metabolism and mitochondrial function in the SHR-Retn versus nontransgenic SHR controls. We observed that interscapular BAT isolated from SHR-Retn transgenic rats when compared to SHR controls showed a lower relative weight (0.71±0.05 vs. 0.91±0.08 g/100 g body weight, P<0.05), significantly reduced both basal and insulin stimulated incorporation of palmitate into BAT lipids (658±50 vs. 856±45 and 864±47 vs. 1086±35 nmol/g/2h, P<=0.01, respectively), and significantly decreased palmitate oxidation (37.6±4.5 vs. 57±4.1 nmol/g/2h, P=0.007) and glucose oxidation (277±34 vs. 458±38 nmol/g/2h, P=0.001). In addition, in vivo microPET imaging revealed significantly reduced 18F-FDG uptake in BAT induced by exposure to cold in SHR-Retn versus control SHR (232±19 vs. 334±22 kBq/cc*ccm, P<0.05). Gene expression profiles identified differentially expressed genes involved in skeletal muscle and connective tissue developmental and inflammation, as well as MAPK and insulin signaling.

These results provide compelling evidence that autocrine effects of resisitin in BAT play an important role in the pathogenesis of insulin resistance in the rat.


O2k-Network Lab: CZ Prague Houstek J, CZ Hradec Kralove Cervinkova Z


Labels: MiParea: Comparative MiP;environmental MiP  Pathology: Diabetes, Obesity 

Organism: Rat  Tissue;cell: Fat 




Event: E1, Oral, Poster  MiP2015 

Affiliations

1-Inst Physiology, Czech Acad Sc; 2-Inst Mol Genetics, Czech Acad Sc; 3-Nuclear Physics Inst, Czech Acad Sc, Husinec-Řež; 4-Fac Pharmacy, Charles Univ Prague, Hradec Králové; 5-Inst Clinical Experimental Med, Prague, Czech Republic. - alena.pecinova@fgu.cas.cz

Figures

MiP2015 Pecinova Figure.JPG

Acknowledgements

Research relating to this abstract was funded by ERC CZ LL1204 and Grant Agency of the Czech Republic (14-36804G).