Inhibition of satiety neuropeptides is related to low expression of pERK and Egr1 in diet‐induced obesity

Abstract

Leptin stimulates the production of appetite‐inhibiting peptides POMC/CART in hypothalamus. However, reduced expression of POMC/CART despite an elevated leptin level has been reported in diet‐induced obesity (DIO). We investigated the changes in leptin receptor signaling molecules to understand the mechanisms of decreased POMC/CART in DIO.C57BL mice were fed diets with 10% (Control) or 60% energy from fat (HFD) for 16 weeks. Hypothalamic mRNA levels of neuropeptides CART, POMC, AGRP, and NPY, and signaling molecules Egr1, p35, and SOCS3 were determined. Hypothalamic protein expression of pSTAT3, STAT3, pSHP2, SHP2, pERK1/2 and ERK1/2, and serum leptin and free‐fatty acids were determined.Consumption of HFD resulted in significantly more weight gain (29.9±0.4g in HFD vs. 14.1±0.7g in control), and higher leptin and free‐fatty acids. Hypothalamus from HFD group expressed significantly lower CART, POMC, AgRP, NPY, Egr1, and p35 mRNA but higher SOCS3 mRNA. pSTAT3 and pERK1/2 protein expressions were lower in the HFD group but there was no difference in pSHP2 expression.Results from this study showed that leptin receptor signaling pathways via pERK‐Egr1 and pSTAT3‐p35 were reduced in DIO. Lower expression of POMC/CART despite an elevated leptin level in DIO seems to be related to overexpression of SOCS3 and impaired leptin receptor signaling due to lower pERK1/2, Egr1, pSTAT3, and p35 expression. Supported by the grant from National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (KRF‐331–2008‐C00305)