PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-2 (2)
 

Clipboard (0)
None
Journals
Authors
Year of Publication
Document Types
author:("ree, Karen")
1.  The lipin protein family: dual roles in lipid biosynthesis and gene expression 
FEBS letters  2007;582(1):90-96.
The prevalence of obesity in the western world has focused attention on factors that influence triglyceride biosynthesis, storage, and utilization. Members of the lipin protein family have a newly discovered enzymatic role in triglyceride and phospholipid biosynthesis as a phosphatidate phosphatase, and also act as an inducible transcriptional coactivator in conjunction with PGC-1α and PPARα. Through these activities, the founding member of the family, lipin-1, influences lipid metabolism and glucose homeostasis in diverse tissues including adipose tissue, skeletal muscle, and liver. The physiological roles of lipin-2 and lipin-3 are less well defined, but are likely to carry out similar functions in glycerolipid biosynthesis and gene expression in a distinct tissue distribution.
doi:10.1016/j.febslet.2007.11.014
PMCID: PMC2848953  PMID: 18023282
adipose tissue; ipodystrophy; obesity; triaclyglycerol; phosphatidate phosphatase; transcriptional coactivator
2.  Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models 
Human Molecular Genetics  2009;18(6):1006-1016.
In addition to the hallmark neurological manifestations of Huntington's disease (HD), weight loss with metabolic dysfunction is often observed in the later stages of disease progression and is associated with poor prognosis. The mechanism for weight loss in HD is unknown. Using two mouse models of HD, the R6/2 transgenic and CAG140 knock-in mouse strains, we demonstrate that adipose tissue dysfunction is detectable at early ages and becomes more pronounced as the disease progresses. Adipocytes acquire a ‘de-differentiated’ phenotype characterized by impaired expression of fat storage genes. In addition, HD mice exhibit reduced levels of leptin and adiponectin, adipose tissue-derived hormones that regulate food intake and glucose metabolism. Importantly, some of these changes occur prior to weight loss and development of some of the characteristic neurological symptoms. We demonstrate that impaired gene expression and lipid accumulation in adipocytes can be recapitulated by expression of an inducible mutant huntingtin transgene in an adipocyte cell line and that mutant huntingtin inhibits transcriptional activity of the PGC-1α co-activator in adipocytes, which may contribute to aberrant gene expression. Thus, our findings indicate that mutant huntingtin has direct detrimental effects in cell types other than neurons. The results also indicate that circulating adipose-tissue-derived hormones may be accessible markers for HD prognosis and progression and suggest that adipose tissue may be a useful therapeutic target to improve standard of life for HD patients.
doi:10.1093/hmg/ddn428
PMCID: PMC2649017  PMID: 19124532

Results 1-2 (2)