Format

Send to

Choose Destination
Biochim Biophys Acta. 2010 Mar;1801(3):350-61. doi: 10.1016/j.bbalip.2009.09.016. Epub 2009 Sep 29.

Hypothalamic lipotoxicity and the metabolic syndrome.

Author information

1
Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela, A Coruña, 15782, Spain.

Abstract

Ectopic accumulation of lipids in peripheral tissues, such as pancreatic beta cells, liver, heart and skeletal muscle, leads to lipotoxicity, a process that contributes substantially to the pathophysiology of insulin resistance, type 2 diabetes, steatotic liver disease and heart failure. Current evidence has demonstrated that hypothalamic sensing of circulating lipids and modulation of hypothalamic endogenous fatty acid and lipid metabolism are two bona fide mechanisms modulating energy homeostasis at the whole body level. Key enzymes, such as AMP-activated protein kinase (AMPK) and fatty acid synthase (FAS), as well as intermediate metabolites, such as malonyl-CoA and long-chain fatty acids-CoA (LCFAs-CoA), play a major role in this neuronal network, integrating peripheral signals with classical neuropeptide-based mechanisms. However, one key question to be addressed is whether impairment of lipid metabolism and accumulation of specific lipid species in the hypothalamus, leading to lipotoxicity, have deleterious effects on hypothalamic neurons. In this review, we summarize what is known about hypothalamic lipid metabolism with focus on the events associated to lipotoxicity, such as endoplasmic reticulum (ER) stress in the hypothalamus. A better understanding of these molecular mechanisms will help to identify new drug targets for the treatment of obesity and metabolic syndrome.

PMID:
19796707
DOI:
10.1016/j.bbalip.2009.09.016
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center