This study was conducted to test the hypothesis that dietary arginine supplementation
reduces fat mass in diet-induced obese rats. Male Sprague-Dawley rats were fed either
low- or high-fat diets for 15 wks (16 rats/diet). Thereafter, lean or obese rats continued
to be fed their same respective diets and received drinking water containing either 1.51%
L-arginine-HCl or 2.55% alanine (isonitrogenous control) (n=8/treatment group).
Twelve weeks after the initiation of the arginine treatment, rats were euthanized to
obtain tissues for biochemical analyses. Results were statistically analyzed as a 2x2
factorial experimental design using ANOVA. High-fat diet increased the mass of white
adipose tissues at different anatomical locations by 49-96% compared to the low-fat diet.
Concentrations of serum cholesterol as well as lipids in skeletal muscle and liver were
higher in obese rats than in lean rats. L-Arginine supplementation reduced white adipose
tissue mass by 20-40% while increasing brown adipose tissue mass by 15-20%. In
addition, arginine treatment decreased adipocyte size, serum concentrations of glucose,
triglycerides and leptin, improved glucose tolerance, and enhanced glucose and oleic acid oxidation in skeletal muscles. The mRNA levels for hepatic fatty acid synthase and
stearoyl-CoA desaturase were reduced, but mRNA levels for hepatic AMP-activated
protein kinase (AMPK), PPAR coactivator-1 and carnitine palmitoyltransferase I
(CPT-I) as well as muscle CPT-I were increased in response to the arginine treatment.
Subsequent experiments were conducted with cell models to define the direct effects of
arginine on energy-substrate metabolism in insulin-sensitive cells. In BNL CL.2 mouse
hepatocytes, C2C12 mouse myotubes and 3T3-L1 mouse adipocytes, increasing
extracellular concentrations of arginine from 0 to 400 µM increased AMPK expression
as well as glucose and oleic acid oxidation. Inhibition of nitric oxide synthesis
moderately attenuated the arginine-stimulated increases of substrate oxidation as well as
AMPK and ACC phosphorylation in BNL CL.2 cells, but had no effect in C2C12 and
3T3-L1 cells. Collectively, these results suggest that arginine increases AMPK
expression and energy-substrate oxidation in a cell-specific manner, thereby reducing fat
mass in diet-induced obese rats. The findings have important implications for treating
obesity in humans and companion animals as well as decreasing fat deposition in
livestock species.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-1948 |
| Date | 02 June 2009 |
| Creators | Jobgen, Wenjuan Shi |
| Contributors | Wu, Guoyao |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | electronic, application/pdf, born digital |
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