Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Jul;10(1):9-12.
doi: 10.1016/j.cmet.2009.03.011.

As a matter of fat

Rita T Brookheart  1 , Carlos I Michel, Jean E Schaffer
Affiliations
Review

As a matter of fat

Rita T Brookheart et al. Cell Metab. 2009 Jul.

Abstract

Excess fatty acid accumulation in nonadipose tissues is a hallmark of metabolic disease. When elevated lipid levels exceed the cell's capacity to store or utilize fatty acids, a lipotoxic-response is elicited, characterized by destruction of organelle membranes, activation of stress pathways, and apoptosis. This Minireview focuses on the mechanisms by which lipid overload causes nonadipose cell death and contributes to the pathogenesis of obesity and diabetes.

PubMed Disclaimer

Figures

Figure 1
Figure 1. The lipotoxic-response
In non-adipose cells, excess saturated FFAs induce oxidative and ER stress through lipid metabolites and signaling pathways. Dysfunction of mitochondria and the ER are key steps through which excess lipid induces cell death, whereas channeling of excess FFAs to lipid droplets is cytoprotective.
See this image and copyright information in PMC

References

    1. Borradaile NM, Buhman KK, Listenberger LL, Magee CJ, Morimoto ET, Ory DS, Schaffer JE. A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death. Mol Biol Cell. 2006a;17:770–778. - PMC - PubMed
    1. Borradaile NM, Han X, Harp JD, Gale SE, Ory DS, Schaffer JE. Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res. 2006b;47:2726–2737. - PubMed
    1. Brookheart RT, Michel CI, Listenberger LL, Ory DS, Schaffer JE. The non-coding RNA gadd7 is a regulator of lipid-induced oxidative and ER stress. J Biol Chem. 2009 in press. - PMC - PubMed
    1. Cacicedo JM, Benjachareowong S, Chou E, Ruderman NB, Ido Y. Palmitate-induced apoptosis in cultured bovine retinal pericytes: roles of NAD(P)H oxidase, oxidant stress, and ceramide. Diabetes. 2005;54:1838–1845. - PubMed
    1. Cacicedo JM, Yagihashi N, Keaney JF, Jr, Ruderman NB, Ido Y. AMPK inhibits fatty acid-induced increases in NF-kappaB transactivation in cultured human umbilical vein endothelial cells. Biochem Biophys Res Commun. 2004;324:1204–1209. - PubMed

Publication types