Dietary L-Arginine Supplementation Reduces Fat Mass in Zucker Diabetic Fatty Rats

Abstract

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.

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover

“…hypertension, hyperlipidaemia, renal or hepatic disease, or diabetes. Further, we demonstrated elevations of all three MA in obesity, as reported in the Zucker rat [37]. Most prior human studies have reported only on ADMA, some also on SDMA, but rarely on all three.…”

The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats

“…There may be a higher peripheral utilisation of arginine by arginase at the expense of inducible NO synthase. Hypoargininaemia is clearly related to arginine availability, since a recent study showed that an arginine-supplemented diet improved NOx production in the serum of ZDF rats [22]. Our data demonstrated a depletion of glutamine, in accord with a recent study [13] reporting a decrease in plasma concentrations of several gluconeogenic amino acids in ZDF rats.…”

Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects

“…It is plausible therefore that improvements in muscle blood flow, and insulin sensitivity, which occur secondarily to improvements in endothelial function may be useful for the prevention or management of obesity. Supplementation with L-arginine, the primary substrate for NO, in Zucker diabetic fatty rats increased NO production by 71-85% and attenuated increases in fat mass over 10 weeks compared to those supplemented with alanine, 9 indicating a role of improved endothelial function in obesity management. More direct evidence of a potential role of cocoa in this was provided by a recent Japanese study.…”

“…Indirect support for this hypothesis comes from studies that have shown that the consumption of flavanol-containing cocoa products, and L-arginine (the primary substrate for NO), not only improve FMD, 7 but also reduce body fat. 8,9 Aerobic exercise is strongly advocated for increasing energy expenditure and reducing fat stores, but the amount of exercise required to achieve weight loss may be difficult to achieve for obese individuals who are unaccustomed to exercise. 10 However, if cocoa flavanols can improve circulatory function and fat metabolism, it may result in an augmentation of substrate utilization and/or energy expenditure during exercise.…”