Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet

Abstract

Background: Studies suggest that leucine supplementation (LS) has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET) as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD) in rats.

Methods: Forty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (n = 10) or HFD (n = 37). After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (n = 7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-α) were analyzed.

Results: At the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P = 0.019). In addition, ET was more effective than LS in reducing adiposity (P = 0.019), serum insulin (P = 0.022) and TNF-α (P = 0.044). Conversely, LS increased serum adiponectin (P = 0.021) levels and reduced serum total cholesterol concentration (P = 0.042).

Conclusions: The results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration.

Figure 1

Effect of chronic exercise training and/or leucine supplementation on body weight changes. (A) Body weight. ^#, effect of training in fifth week (P = 0.045); + vs week 1 (P < 0.002). (B) Total body weight variation (final - initial body weight). *, effect of diet (P = 0.028); ^#, effect of training, (P = 0.006). Experimental groups: control diet (REF), diet supplemented with 5% L-leucine (LS), 6 weeks of endurance training (ET) plus standard diet, and diet supplemented with 5% L-leucine plus endurance training (LS+ET). Values are mean ± sem (n = 7-8 rats per group).

Figure 2

Chronic exercise is more efficient than leucine supplementation in reducing adiposity. (A) Body composition (%). ^#, effect of training (P < 0.019). (B) Epididymal adipocyte volume. ^#, effect of training (P < 0.005); *, effect of diet, (P <0.020). (C) Epididymal adipocyte number ^#, effect of training (P < 0.044). Experimental groups: control diet (REF), diet supplemented with 5% L-leucine (LS), 6 weeks of endurance training (ET) plus standard diet, and diet supplemented with 5% L-leucine plus endurance training (LS+ET). Values are mean ± sem (n = 7-8 rats per group).

Figure 3

Leucine supplementation reduces serum total cholesterol levels in sedentary animals. (A) Serum concentration of triacylglycerol. (B) Serum concentration of cholesterol. *, effect of diet (P <0.042); interaction of the two factors (P = 0.018). (C) Serum concentration of HDL-cholesterol. (D) Serum concentration of glucose. (E) Serum concentration of Insulin. ^#, effect of training (P < 0.022). Experimental groups: control diet (REF), diet supplemented with 5% L-leucine (LS), 6 weeks of endurance training (ET) plus standard diet, and diet supplemented with 5% L-leucine plus endurance training (LS+ET). Values are mean ± sem (n = 5-8 rats per group).

Figure 4

Leucine supplementation increases adiponectin levels. (A) Adiponectin. *, effect of diet (P <0.021). (B) TNF-α. ^#, effect of training (P < 0.044). (C) Leptin. Experimental groups: control diet (REF), diet supplemented with 5% L-leucine (LS), 6 weeks of endurance training (ET) plus standard diet, and diet supplemented with 5% L-leucine plus endurance training (LS+ET). Values are mean ± sem (n = 6-8 rats per group).

Figure 5

Effect of chronic exercise and/or leucine supplementation on circulating levels of amino acids. ^#, effect of training (P < 0.05); *, interaction for amino acids glycine and threonine (P <0.05). Experimental groups: control diet (REF), diet supplemented with 5% L-leucine (LS), 6 weeks of endurance training (ET) plus standard diet, and diet supplemented with 5% L-leucine plus endurance training (LS+ET). Values are mean ± sem (n = 5-4 rats per group).