Hyperphagic obesity in adult dicer CKO mice: the role of hypothalamic AgRP/NPY neurons

• Autorzy: Hajdukiewicz K. , Stefaniuk M. , Grinievich V. , Konopka W.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Obesity is a worldwide disease of complex etiology. The main appetite regulatory center is located within the brain, in the hypothalamus. A putative mechanism responsible for the obesity phenotype involves microRNA interplay between feeding regulatory elements of the hypothalamic AgRP/NPY-expressing, POMC-producing and probably other arcuate nucleus neurons. Dicer is a key enzyme in microRNA processing. In Dicer’s absence, there is a pronounced lack of mature microRNAs and a disturbed regulation of translation. AIM(S): We want to observe how massive, spatially and temporally defined, loss of microRNAs impacts metabolism and obesity outcome. METHOD(S): We injected rAAV-coding Cre recombinase under the AgRP specific promoter into the arcuate nucleus of mice with a Cre- dependent Dicer sequence. As NPY is a known appetite stimulator, to determine whether NPY is the key player in this phenotype, we induced Dicer loss in NPY knockout (KO) mice via Tamoxifen IP injections. RESULTS: Our preliminary data show that administration of AAV-AgRP- Cre construct leads to visible weight gain, correlated with increased food intake. This phenotypic effect is AAV‑dose‑dependent and is likely accompanied by an imbalance between anorexygenic and orexigenic neuropeptide levels. However, NPY KO mice with massive microRNA loss gradually put on weight, though with different kinetics as compared to Dicer CKO mice. CONCLUSIONS: Our approach demonstrates that microRNA loss in a subpopulation of arcuate nucleus neurons has a very pronounced effect on the central regulation of metabolism, expressed by weight gain as well as hyperphagy. Moreover, it is likely the mechanism involves an extensive system of complex relationships because loss of single-gene coding of the main orexigenic neuropeptide (NPY) does not inhibit weight gain. Nevertheless, the exact mechanism underlying this phenomenon has not yet been elucidated.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.93

Twórcy

autor

Hajdukiewicz K.

• Laboratory of Animal Models, Neurobiology Center, Nencki Institute of Experimental Biology, Warsaw, Poland

autor

Stefaniuk M.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Warsaw, Poland

autor

Grinievich V.

• Schaller Research Group on Neuropeptides, German Cancer Research Center and University of Heidelberg, Heidelberg, Germany

autor

Konopka W.

• Laboratory of Animal Models, Neurobiology Center, Nencki Institute of Experimental Biology, Warsaw, Poland