Journal
FASEB JOURNAL
Volume 15, Issue 2, Pages 312-321Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.00-0590
Keywords
-
Categories
Funding
- NIDDK NIH HHS [DK02700-37] Funding Source: Medline
Ask authors/readers for more resources
Obesity-related diseases now threaten to reach epidemic proportions in the United States, Here we review in a rodent model of genetic obesity, the fa/fa Zucker diabetic fatty (ZDF) rat, the mechanisms involved in the most common complications of diet-induced human obesity, i.e., noninsulin-dependent diabetes mellitus, and myocardial dysfunction. In ZDF rats, hyperphagia leads to hyperinsulinemia, which upregulates transcription factors that stimulate lipogenesis. This causes ectopic deposition of triacylglycerol in nonadipocytes, providing fatty acid (FA) substrate for damaging pathways of nonoxidative metabolism, such as ceramide synthesis, In beta cells and myocardium, the resulting functional impairment and apoptosis cause diabetes and cardiomyopathy, Interventions that lower ectopic lipid accumulation or block nonoxidative metabolism of FA and ceramide formation completely prevent these complications, Given the evidence for a similar etiology for the complications of human obesity, it would be appropriate to develop strategies to avert the predicted epidemic of lipotoxic disorders.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available