| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Discovery Technologies Area, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA
2 the Diabetes and Metabolism Area, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA
* To whom correspondence should be addressed. E-mail: didier.laurent{at}pharma.novartis.com.
High visceral adiposity and intramyocellular lipid levels (IMCL) are both associated with the
development of type 2 diabetes. The relationship between visceral adiposity and IMCL levels
was explored in a diet-induced and a glucocorticoid-induced model of insulin resistance. In
the diet-induced model, lean and fa/fa Zucker rats were fed either a normal or a high-fat (HF)
chow over a 4-week period. Fat distribution, IMCL content in the tibialis anterior (IMCLTA)
muscle and whole-body insulin resistance were measured prior to and following the 4-week
period. The HF diet-induced increase in IMCLTA was strongly correlated with visceral fat
accumulation and greater glucose intolerance in both groups of rats. The increase in IMCLTA
to visceral fat accumulation was three-fold greater for fa/fa rats. In the glucocorticoid-induced
model, insulin sensitivity was impaired using dexamethasone. In-vivo adiposity and IMCLTA
content measurements were combined with ex-vivo analysis of plasma and muscle tissue.
Dexamethasone treatment had minimal effect on visceral fat accumulation, while increasing
IMCLTA levels by ~30% (p<0.05) compared to controls. Dexamethasone increased plasma
glucose by 2-fold, and increased the saturated fatty acid content of plasma lipids (fatty acid
(CH2)n/
CH3 ratio +15%, p<0.05). The lipid composition of the TA muscle was unchanged by
dexamethasone treatment indicating that the relative increase in IMCLTA observed in-vivo
resulted from a decrease in lipid oxidation. Visceral adiposity may influence IMCL
accumulation in the context of dietary manipulations; however a "causal" relationship still
remains to be determined. Dexamethasone-induced insulin resistance likely operates under a
different mechanism, i.e. independently of visceral adiposity.
This article has been cited by other articles:
|
|
 |
|
  S. S. Velan, N. Said, C. Durst, S. Frisbee, J. Frisbee, R. R. Raylman, M. A. Thomas, V. M. Rajendran, R. G. Spencer, and S. E. Alway Distinct patterns of fat metabolism in skeletal muscle of normal-weight, overweight, and obese humans Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1060 - R1065. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Didier, B. Yerby, R. Deacon, and J. Gao Diet-induced modulation of mitochondrial activity in rat muscle Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1169 - E1177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Berthiaume, M. Laplante, W. T. Festuccia, K. Cianflone, L. P. Turcotte, D. R. Joanisse, G. Olivecrona, R. Thieringer, and Y. Deshaies 11beta-HSD1 inhibition improves triglyceridemia through reduced liver VLDL secretion and partitions lipids toward oxidative tissues Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1045 - E1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Aslanidi, V. Kroutov, G. Philipsberg, K. Lamb, M. Campbell-Thompson, G. A. Walter, S. Kurenov, J. Ignacio Aguirre, P. Keller, K. Hankenson, et al. Ectopic expression of Wnt10b decreases adiposity and improves glucose homeostasis in obese rats Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E726 - E736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Beha, H.-P. Juretschke, J. Kuhlmann, C. Neumann-Haefelin, U. Belz, M. Gerl, W. Kramer, M. Roden, and A. W. Herling Muscle type-specific fatty acid metabolism in insulin resistance: an integrated in vivo study in Zucker diabetic fatty rats Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E989 - E997. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
