Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats
Open accessAbstract
This study was conducted to test the hypothesis that dietary supplementation of arginine, the physiologic precursor of nitric oxide (NO), reduces fat mass in the Zucker diabetic fatty (ZDF) rat, a genetically obese animal model of type-II diabetes mellitus. Male ZDF rats, 9 wk old, were pair-fed Purina 5008 diet and received drinking water containing arginine-HCl (1.51%) or alanine (2.55%, isonitrogenous control) for 10 wk. Serum concentrations of arginine and NO(x) (oxidation products of NO) were 261 and 70% higher, respectively, in arginine-supplemented rats than in control rats. The body weights of arginine-treated rats were 6, 10, and 16% lower at wk 4, 7, and 10 after the treatment initiation, respectively, compared with control rats. Arginine supplementation reduced the weight of abdominal (retroperitoneal) and epididymal adipose tissues (45 and 25%, respectively) as well as serum concentrations of glucose (25%), triglycerides (23%), FFA (27%), homocysteine (26%), dimethylarginines (18-21%), and leptin (32%). The arginine treatment enhanced NO production (71-85%), lipolysis (22-24%), and the oxidation of glucose (34-36%) and octanoate (40-43%) in abdominal and epididymal adipose tissues. Results of the microarray analysis indicated that arginine supplementation increased adipose tissue expression of key genes responsible for fatty acid and glucose oxidation: NO synthase-1 (145%), heme oxygenase-3 (789%), AMP-activated protein kinase (123%), and peroxisome proliferator-activated receptor gamma coactivator-1alpha (500%). The induction of these genes was verified by real-time RT-PCR analysis. In sum, arginine treatment may provide a potentially novel and useful means to enhance NO synthesis and reduce fat mass in obese subjects with type-II diabetes mellitus.
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Dietary L-arginine supplementation in rats reduces fat mass, increases skeletal muscle and brown fat mass, and reduces serum concentrations of glucose, triglycerides, free fatty acids, homocysteine, dimethylarginines, and leptin.
“In rats, not only has dietary L-arginine supplementation been shown to reduce fat mass, but it appears to increase skeletal muscle and brown fat mass and reduce serum concentrations of glucose, triglycerides, free fatty acids, homocysteine, dimethylarginines, and leptin as well [279, 280].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [279]
Rice endosperm protein is high in arginine, a precursor of nitric oxide, which is depleted in the diabetic rat model.
“Another potential explanation is that a protein such as rice endosperm protein is high in arginine, a precursor of nitric oxide (NO), which is depleted in this rat model [105,106].”
From Plant Proteins: Assessing Their Nutritional Quality and Effects on Health and Physical Function (2020) · cites this paper as [106]
Improvement of renal hemodynamics resulting from arginine supplementation could be the direct result of an increase in nitric oxide production.
“The improvement of renal hemodynamics which results from the supplementation of arginine could be the direct result of an increase in NO production [106].”
From Plant Proteins: Assessing Their Nutritional Quality and Effects on Health and Physical Function (2020) · cites this paper as [106]
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“tions of glucose, triglycerides, free fatty acids, homocysteine, dimethylarginines, and leptin as well [279,280].”
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- Authors
- Fu, W. J., Haynes, T. E., Kohli, R., Hu, J., Shi, W., Spencer, T. E., Carroll, R. J., Meininger, C. J., & Wu, G.
- Affiliations
- Texas A&M University (US)
- Texas A&M Health Science Center (US)
- Corresponding author
- Wu, Guoyao
- ORCID
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 135
- Issue
- 4
- Pages
- 714-721
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2138419214
- Cited by
- 353
- References
- 53
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 17 · 2021: 16 · 2020: 16 · 2019: 20 · 2018: 13 · 2017: 21 · 2016: 19 · 2015: 22 · 2014: 24 · 2013: 22 · 2012: 22
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (5r21hl077401-02, ES09106, R25 CA90301, CA57030)
- National Heart, Lung, and Blood Institute (R21HL077401-01, ES09106, R21 HL077401)
- National Cancer Institute (CA 90301, R25 CA90301, R25CA090301, CA 57030)
- National Institute of Environmental Health Sciences (P30ES009106, P30‐ES09106)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- arginine supplementation, nitric oxide, fat mass, Zucker diabetic fatty rats, type 2 diabetes, obesity, adipose tissue lipolysis, fatty acid oxidation, glucose oxidation, AMPK, PPARγ coactivator-1α, leptin, dimethylarginines, homocysteine, triglycerides, fatty acid binding protein
- MeSH terms
- Abdomen, Adipose Tissue, Animals, Arginine, Blood Glucose, Diabetes Mellitus, Type 2, Hormones, Lipids, Male, Nitrogen Oxides, Obesity, Rats, Zucker, DNA Primers, Dietary Supplements, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Rats
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