• Publications
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Triglyceride accumulation protects against fatty acid-induced lipotoxicity
TLDR
This work demonstrates in cultured cells that the relative toxicity of two common dietary long chain fatty acids is related to channeling of these lipids to distinct cellular metabolic fates, and supports a model of cellular lipid metabolism in which unsaturated fatty acids serve a protective function against lipotoxicity though promotion of triglyceride accumulation.
Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein
TLDR
Immunocytochemistry and subcellular fractionation of 3T3-L1 adipocytes show that FATP is localized to the plasma membrane, and it is proposed thatfatP is a plasma membrane transporter for LCFAs.
Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death Published, JLR Papers in Press, September 7, 2006.
TLDR
Palmitate rapidly increases the saturated lipid content of the ER, leading to compromised ER morphology and integrity, suggesting that impairment of the structure and function of this organelle is involved in the cellular response to fatty acid overload.
Niemann-Pick Type C1 I1061T Mutant Encodes a Functional Protein That Is Selected for Endoplasmic Reticulum-associated Degradation Due to Protein Misfolding*
TLDR
These findings provide the first description of an endoplasmic reticulum trafficking defect as a mechanism for human NPC disease, shedding light on the mechanism by which the NPC1I1061T mutation causes disease and suggesting novel approaches to treat NPC disease caused by the NPC 1I10 61T mutation.
A novel mouse model of lipotoxic cardiomyopathy.
TLDR
It is demonstrated that fatty acid uptake/utilization mismatch in the heart leads to accumulation of lipid species toxic to cardiac myocytes, and a novel mouse model of metabolic cardiomyopathy is established to provide insight into the role of perturbations in myocardial lipid metabolism in the pathogenesis of inherited and acquired forms of heart failure.
Palmitate-induced Apoptosis Can Occur through a Ceramide-independent Pathway*
TLDR
The data suggest that palmitate-induced apoptosis occurs through the generation of reactive oxygen species, independent of ceramide synthesis, is important for the lipotoxic response and may contribute to the pathogenesis of diseases involving intracellular lipid accumulation.
Lipotoxicity: when tissues overeat
  • J. Schaffer
  • Medicine
    Current opinion in lipidology
  • 1 June 2003
TLDR
Critical in this process are physiologic mechanisms for directing excess free fatty acids to specific tissues as well as cellular mechanisms for channeling excess fatty acid to particular metabolic fates, which may contribute to the development of more effective therapies for common human disorders.
Diet-induced obesity model: abnormal oocytes and persistent growth abnormalities in the offspring.
TLDR
These findings suggest maternal obesity has adverse effects as early as the oocyte and preimplantation embryo stage and that these effects may contribute to lasting morbidity in offspring, underscoring the importance of optimal maternal weight and nutrition before conception.
NPC1 and NPC2 Regulate Cellular Cholesterol Homeostasis through Generation of Low Density Lipoprotein Cholesterol-derived Oxysterols*
TLDR
Findings support a role for NPC1 and NPC2 in the regulation of sterol homeostasis through generation of LDL cholesterol-derived oxysterols and have important implications for the treatment of NPC disease.
Cholesterol Oxidation Products Are Sensitive and Specific Blood-Based Biomarkers for Niemann-Pick C1 Disease
TLDR
Blood concentrations of two related oxysterols molecules were almost 10 times higher in Niemann-Pick C1 patients than in age-matched healthy controls or those with other diseases such as atherosclerosis or diabetes, suggesting that the two oxysterol molecules are accurate diagnostic markers of early clinical disease and can be used not only to monitor disease progression but also to demonstrate drug efficacy.
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