Format

Send to

Choose Destination
Mitochondrion. 2008 Sep;8(4):329-37. doi: 10.1016/j.mito.2008.02.001. Epub 2008 Feb 26.

Nuclear receptors, mitochondria and lipid metabolism.

Author information

1
Gene Expression Laboratory,The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, United States. alaynick@salk.edu

Abstract

Lipid metabolism is a continuum from emulsification and uptake of lipids in the intestine to cellular uptake and transport to compartments such as mitochondria. Whether fats are shuttled into lipid droplets in adipose tissue or oxidized in mitochondria and peroxisomes depends on metabolic substrate availability, energy balance and endocrine signaling of the organism. Several members of the nuclear hormone receptor superfamily are lipid-sensing factors that affect all aspects of lipid metabolism. The physiologic actions of glandular hormones (e.g. thyroid, mineralocorticoid and glucocorticoid), vitamins (e.g. vitamins A and D) and reproductive hormones (e.g. progesterone, estrogen and testosterone) and their cognate receptors are well established. The peroxisome-proliferator activated receptors (PPARs) and liver X receptors (LXRs), acting in concert with PPARgamma Coactivator 1alpha (PGC-1alpha), have been shown to regulate insulin sensitivity and lipid handling. These receptors are the focus of intense pharmacologic studies to expand the armamentarium of small molecule ligands to treat diabetes and the metabolic syndrome (hypertension, insulin resistance, hyperglycemia, dyslipidemia and obesity). Recently, additional partners of PGC-1alpha have moved to the forefront of metabolic research, the estrogen-related receptors (ERRs). Although no endogenous ligands for these receptors have been identified, phenotypic analyses of knockout mouse models demonstrate an important role for these molecules in substrate sensing and handling as well as mitochondrial function.

PMID:
18375192
PMCID:
PMC2831104
DOI:
10.1016/j.mito.2008.02.001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center