Elsevier

Biochimie

Volume 176, September 2020, Pages 110-116
Biochimie

Lipid excess affects chaperone-mediated autophagy in hypothalamus

https://doi.org/10.1016/j.biochi.2020.06.008Get rights and content
Under an Elsevier user license
open access

Highlights

  • Short-term high-fat diet enhances hypothalamic cytokines expression.

  • High-fat diet induces changes in chaperone-mediated autophagy machinery.

  • Acute palmitate treatment enhances neuronal chaperone-mediated autophagy.

Abstract

Obesity is a major health problem worldwide. Overweight and obesity directly affect health-related quality of life and also have an important economic impact on healthcare systems. In experimental models, obesity leads to hypothalamic inflammation and loss of metabolic homeostasis. It is known that macroautophagy is decreased in the hypothalamus of obese mice but the role of chaperone-mediated autophagy is still unknown. In this study, we aimed to investigate the role of hypothalamic chaperone-mediated autophagy in response to high-fat diet and also the direct effect of palmitate on hypothalamic neurons. Mice received chow or high-fat diet for 3 days or 1 week. At the end of the experimental protocol, chaperone-mediated autophagy in hypothalamus was investigated, as well as cytokines expression. In other set of experiments, neuronal cell lines were treated with palmitic acid, a saturated fatty acid. We show that chaperone-mediated autophagy is differently regulated in response to high-fat diet intake for 3 days or 1 week. Also, when hypothalamic neurons are directly exposed to palmitate there is activation of chaperone-mediated autophagy. High-fat diet causes hypothalamic inflammation concomitantly to changes in the content of chaperone-mediated autophagy machinery. It remains to be studied the direct role of inflammation and lipids itself on the activation of chaperone-mediated autophagy in the hypothalamus in vivo and also the neuronal implications of chaperone-mediated autophagy inhibition in response to obesity.

Keywords

Autophagy
Hypothalamus
Obesity
Palmitic acid
Chaperone-mediated autophagy

Abbreviations

CMA
chaperone-mediated autophagy
FBS
fetal bovine serum
HCS
High-content screening
HFD
High-fat diet

Cited by (0)

1

Present Adress: Laboratory of Immunoinflammation, Institute of Biology, UNICAMP, Campinas, 13083-862, Brazil.

2

Present Adress: Paris-Saclay Institute of Neuroscience, Université Paris-Sud, University Paris Saclay, Orsay, CNRS UMR 9197, France.