In vivo multi-tissue efficacy of peroxisome proliferator-activated receptor-γ therapy on glucose and fatty acid metabolism in obese type 2 diabetic rats
Author contributions: SN and SR analyzed and interpreted the data and contributed to writing this manuscript. KS analyzed, interpreted, contributed to writing the manuscript, and approved the final version for publication.
Funding agencies: This work was supported by NIH (Grant No. 5R01DK085298). The work utilized core services provided by the Diabetes Research Center (DRC) (Grant No. P60DK020579), and the Nutrition Obesity Research Center (NORC) (Grant No. P30DK056341).
Disclosure: The authors have no conflicts of interest to report.
To identify the disturbances in glucose and lipid metabolism observed in type 2 diabetes mellitus, we examined the interaction and contribution of multiple tissues (liver, heart, muscle, and brown adipose tissue) and monitored the effects of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ) agonist rosiglitazone (RGZ) on metabolism in these tissues.
Design and Methods
Rates of [18F]fluorodeoxyglucose ([18F]FDG) and [11C]Palmitate uptake and utilization in the Zucker diabetic fatty (ZDF) rat were quantified using noninvasive positron emission tomography imaging and quantitative modeling in comparison to lean Zucker rats. Furthermore, we studied two separate groups of RGZ-treated and untreated ZDF rats.
Glucose uptake is impaired in ZDF brown fat, muscle, and heart tissues compared to leans, while RGZ treatment increased glucose uptake compared to untreated ZDF rats. Fatty acid (FA) uptake decreased, but FA flux increased in brown fat and skeletal muscle of ZDF rats. RGZ treatment increased uptake of FA in brown fat but decreased uptake and utilization in liver, muscle, and heart.
Our data indicate tissue-specific mechanisms for glucose and FA disposal as well as differential action of insulin-sensitizing drugs to normalize substrate handling and highlight the role that preclinical imaging may play in screening drugs for obesity and diabetes.