Palmitate-induced autophagy liberates monounsaturated fatty acids and increases Agrp expression in hypothalamic cells

Seokjae Park,Tae Seok Oh,Seolsong Kim,Eun-Kyoung Kim

doi:10.1080/19768354.2019.1696407

Seokjae Park, Tae Seok Oh + Show 2 more

Open Access

https://doi.org/10.1080/19768354.2019.1696407

Copy DOI

Abstract

ABSTRACT Fatty acids regulate food intake, although the exact mechanism remains unknown. Emerging evidence suggests that intracellular free fatty acids generated by starvation-induced autophagy regulate food intake. Starvation for 6 h elevated fatty acids such as palmitate, oleate, arachidonate, eicosatrienoate, and docosahexaenoate in the mouse serum. Among them, palmitate induced lipophagy, an autophagic degradation of cellular lipid droplets, in agouti-related peptide (Agrp)-expressing hypothalamic cells. Palmitate-induced lipophagy increased both Agrp expression and the contents of monounsaturated fatty acids such as palmitoleate, oleate, and (E)-9-octadecanoate, whereas these effects were blunted by autophagy deficiency. These findings support the role of free fatty acids in hypothalamic autophagy that regulates the appetite by changing the expression of orexigenic neuropeptides.

Highlights

Accumulating evidence suggests that hypothalamic lipid metabolism regulates food intake and energy balance in the etiology of metabolic diseases (Lam et al 2005; Lopez et al 2005)
We identified the types of free fatty acids (FFAs) that induce lipophagy and performed metabolomics analysis of FFAs generated by lipophagy that upregulates agoutirelated peptide (Agrp) expression
We demonstrated that lipophagy induced in hypothalamic cells by palmitate, a specific type of saturated fatty acids (SFA), degrades cytosolic lipid droplets (LDs) into intracellular FFAs and increases Agrp expression in hypothalamic cells

Summary

Introduction

Accumulating evidence suggests that hypothalamic lipid metabolism regulates food intake and energy balance in the etiology of metabolic diseases (Lam et al 2005; Lopez et al 2005). Circulating FFAs are a primary fuel source in most tissues during starvation and they are transported through the blood–brain barrier (Spector 1988), which may play a role in the appetite regulation. Fastinginduced circulating FFAs are rapidly taken up by a variety of cells including hypothalamic neurons and esterified to triglycerides within lipid droplets (LDs). Others have reported that i.c.v. infusion of palmitate shows orexigenic effects (Benoit et al 2009; Milanski et al 2009). These results imply distinct regulation of food intake depending on the type of FFA

Methods

Results

Conclusion