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High fat feeding and dietary l-arginine supplementation differentially regulate gene expression in rat white adipose tissue

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Abstract

Dietary l-arginine (Arg) supplementation reduces white-fat gain in diet-induced obese rats but the underlying mechanisms are unknown. This study tested the hypothesis that Arg treatment affects expression of genes related to lipid metabolism in adipose tissue. Four-week-old male Sprague–Dawley rats were fed a low-fat (LF) or high-fat (HF) diet for 15 weeks. Thereafter, lean or obese rats continued to be fed their same respective diets and received drinking water containing 1.51% Arg–HCl or 2.55% l-alanine (isonitrogenous control). After 12 weeks of Arg supplementation, rats were euthanized to obtain retroperitoneal adipose tissue for analyzing global changes in gene expression by microarray. The results were confirmed by RT-PCR analysis. HF feeding decreased mRNA levels for lipogenic enzymes, AMP-activated protein kinase, glucose transporters, heme oxygenase 3, glutathione synthetase, superoxide dismutase 3, peroxiredoxin 5, glutathione peroxidase 3, and stress-induced protein, while increasing expression of carboxypeptidase-A, peroxisome proliferator activated receptor (PPAR)-α, caspase 2, caveolin 3, and diacylglycerol kinase. In contrast, Arg supplementation reduced mRNA levels for fatty acid binding protein 1, glycogenin, protein phosphates 1B, caspases 1 and 2, and hepatic lipase, but increased expression of PPARγ, heme oxygenase 3, glutathione synthetase, insulin-like growth factor II, sphingosine-1-phosphate receptor, and stress-induced protein. Biochemical analysis revealed oxidative stress in white adipose tissue of HF-fed rats, which was prevented by Arg supplementation. Collectively, these results indicate that HF diet and Arg supplementation differentially regulate gene expression to affect energy-substrate oxidation, redox state, fat accretion, and adipocyte differentiation in adipose tissue. Our findings provide a molecular mechanism to explain a beneficial effect of Arg on ameliorating diet-induced obesity in mammals.

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Abbreviations

AA:

Amino acid

AMPK:

AMP-activated protein kinase

Arg:

l-Arginine

DIO:

Diet-induced obese

HF:

High fat

HO-3:

Heme oxygenase 3

LF:

Low fat

NO:

Nitric oxide

PGC1α:

PPARγ coactivator-1α

PPARγ:

Peroxisome proliferator activator receptor γ

RP:

Retroperitoneal

RT-PCR:

Reverse transcriptase-polymerase chain reaction

SCD1:

Stearoyl-CoA desaturase 1

ZDF:

Zucker diabetic fatty

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Acknowledgments

We thank Dr. Laurie Davidson and Mr. Scott Jobgen for technical assistance. This work was supported by National Research Initiative Competitive Grants from the USDA Cooperative State Research, Education, and Extension Service (2008-35206-18762), American Heart Association-TX (0655109Y and 0755024Y), and Texas AgriLife Research (H-8200).

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Authors and Affiliations

  1. Department of Animal Science, Faculty of Nutrition, Texas A&M University, College Station, TX, 77843, USA

    Wenjuan Jobgen, Wenjiang J. Fu, Haijun Gao, Peng Li, Stephen B. Smith, Thomas E. Spencer & Guoyao Wu

  2. Department of Epidemiology, Michigan State University, East Lansing, MI, 48824, USA

    Wenjiang J. Fu

  3. Department of Systems Biology and Translational Medicine, Texas A&M Health Science Center, Temple, TX, 76504, USA

    Cynthia J. Meininger & Guoyao Wu

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  1. Wenjuan Jobgen
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  2. Wenjiang J. Fu
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  3. Haijun Gao
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  4. Peng Li
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  5. Cynthia J. Meininger
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  7. Thomas E. Spencer
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  8. Guoyao Wu
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Correspondence to Guoyao Wu.

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Jobgen, W., Fu, W.J., Gao, H. et al. High fat feeding and dietary l-arginine supplementation differentially regulate gene expression in rat white adipose tissue. Amino Acids 37, 187–198 (2009). https://doi.org/10.1007/s00726-009-0246-7

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  • DOI: https://doi.org/10.1007/s00726-009-0246-7

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