AJP - Renal Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (June 27, 2007). doi:10.1152/ajprenal.00021.2007
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
293/3/F670    most recent
00021.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dominguez, J. H.
Right arrow Articles by Kelly, K. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dominguez, J. H.
Right arrow Articles by Kelly, K. J.
Submitted on January 12, 2007
Accepted on June 22, 2007

Lipotoxic and inflammatory phenotypes in rats with uncontrolled metabolic syndrome and nephropathy

Jesus H. Dominguez1*, Pengfei Wu2, C. Subah Packer3, Constance J Temm2, and Katherine J. Kelly2

1 Dept of Medicine and Physiology, Indiana University School of Med, Indianapolis, Indiana, United States
2 Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States
3 Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana, United States

* To whom correspondence should be addressed. E-mail: jhdoming{at}iupui.edu.

Anomalous inflammatory responses triggered by the metabolic syndrome cause renal injury. This discovery links renal lipid accumulation with lipotoxicity to inflammation, and may explain the insidious fibrosis and cellular decay characteristic of nephropathy in the metabolic syndrome. However, it is not clear if control of inflammation protects the kidney independently of lipid accumulation, which is a required step for lipotoxicity in hyperglycemia and dyslipidemia. We hypothesized that in rats with the metabolic syndrome, and overt nephropathy, treatment with mycophenolate mofetil (MMF, 10 mg/kg/day for 14 weeks, I.P.) would reduce the abnormal renal lipid depots and limit renal inflammation and injury. We studied groups of lean and obese F1 hybrid Zucker Fatty Diabetic/Spontaneous Hypertensive Heart Failure (ZS) rats. MMF did not affect lean rats. In obese ZS rats, MMF did not change severe hyperglycemia or the higher kidney loads of unutilized lipid and peroxidation products. Nonetheless, MMF dramatically reduced diabetes/obesity-derived systemic and renal inflammation, limited renal size, hyperfiltration, and fibrosis. These data indicate that in rats, anti-inflammatory therapy presumably acting downstream, and independently of lipotoxicity, can effectively limit renal injury and fibrosis.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Zhang, Y. Tan, W. Guo, C. Li, S. Ji, X. Li, and L. Cai
Attenuation of diabetes-induced renal dysfunction by multiple exposures to low-dose radiation is associated with the suppression of systemic and renal inflammation
Am J Physiol Endocrinol Metab, December 1, 2009; 297(6): E1366 - E1377.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
X. X. Wang, T. Jiang, Y. Shen, L. Adorini, M. Pruzanski, F. J. Gonzalez, P. Scherzer, L. Lewis, S. Miyazaki-Anzai, and M. Levi
The farnesoid X receptor modulates renal lipid metabolism and diet-induced renal inflammation, fibrosis, and proteinuria
Am J Physiol Renal Physiol, December 1, 2009; 297(6): F1587 - F1596.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. J. Kelly, J. L. Burford, and J. H. Dominguez
Postischemic inflammatory syndrome: a critical mechanism of progression in diabetic nephropathy
Am J Physiol Renal Physiol, October 1, 2009; 297(4): F923 - F931.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
J. E. Toblli, M. G. Ferrini, G. Cao, D. Vernet, M. Angerosa, and N. F. Gonzalez-Cadavid
Antifibrotic effects of pioglitazone on the kidney in a rat model of type 2 diabetes mellitus
Nephrol. Dial. Transplant., August 1, 2009; 24(8): 2384 - 2391.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Y. Wang, W. Feng, W. Xue, Y. Tan, D. W. Hein, X.-K. Li, and L. Cai
Inactivation of GSK-3{beta} by Metallothionein Prevents Diabetes-Related Changes in Cardiac Energy Metabolism, Inflammation, Nitrosative Damage, and Remodeling
Diabetes, June 1, 2009; 58(6): 1391 - 1402.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. G. Goodwill, M. E. James, and J. C. Frisbee
Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension
Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1522 - H1528.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. J. Kelly, P. Wu, C. E. Patterson, C. Temm, and J. H. Dominguez
LOX-1 and inflammation: a new mechanism for renal injury in obesity and diabetes
Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1136 - F1145.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. H. Dominguez, J. L. Mehta, D. Li, P. Wu, K. J. Kelly, C. S. Packer, C. Temm, E. Goss, L. Cheng, S. Zhang, et al.
Anti-LOX-1 therapy in rats with diabetes and dyslipidemia: ablation of renal vascular and epithelial manifestations
Am J Physiol Renal Physiol, January 1, 2008; 294(1): F110 - F119.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.