Although endothelial dysfunction, defined as abnormal vasoreactivity, is a common early finding in individuals with type 2 diabetes, the endothelium has not been known to regulate metabolism. As PPARγ, a transcriptional regulator of energy balance, is expressed in endothelial cells, we set out to investigate the role of endothelial cell PPARγ in metabolism using mice that lack PPARγ in the endothelium and BM (γEC/BM-KO). When γEC/BM-KO mice were fed a high-fat diet, they had decreased adiposity and increased insulin sensitivity compared with control mice, despite increased serum FFA and triglyceride (TG) levels. After fasting or olive oil gavage, γEC/BM-KO mice exhibited significant dyslipidemia and failed to respond to the FFA and TG lowering effects of the PPARγ agonist rosiglitazone. BM transplantation studies, which reconstituted hematopoietic PPARγ, established that these metabolic phenotypes were due to endothelial PPARγ deficiency. We further found that the impairment in TG-rich lipoprotein metabolism in γEC/BM-KO mice was associated with fatty acid–mediated lipoprotein lipase inhibition and changes in a PPARγ-regulated endothelial cell transcriptional program. Despite their metabolic improvements, high-fat diet–fed γEC/BM-KO mice had impaired vasoreactivity. Taken together, these data suggest that PPARγ in the endothelium integrates metabolic and vascular responses and may contribute to the effects of PPARγ agonists, thus expanding what endothelial function and dysfunction may entail.
Takeshi Kanda, Jonathan D. Brown, Gabriela Orasanu, Silke Vogel, Frank J. Gonzalez, Juliano Sartoretto, Thomas Michel, Jorge Plutzky
Usage data is cumulative from February 2019 through February 2020.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.