os. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. Am J Physiol Regul Integr Comp Physiol 287: R1387-R1393, 2004. First published August 26, 2004 doi:10.1152/ajpregu.00159.2004The study investigated the mechanism by which glycine protects against increased circulating nonesterified fatty acids (NEFA), fat cell size, intra-abdominal fat accumulation, and blood pressure (BP) induced in male Wistar rats by sucrose ingestion. The addition of 1% glycine to the drinking water containing 30% sucrose, for 4 wk, markedly reduced high BP in sucrose-fed rats (SFR) (122.3 Ϯ 5.6 vs. 147.6 Ϯ 5.4 mmHg in SFR without glycine, P Ͻ 0.001). Decreases in plasma triglyceride (TG) levels (0.9 Ϯ 0.3 vs. 1.4 Ϯ 0.3 mM, P Ͻ 0.001), intra-abdominal fat (6.8 Ϯ 2.16 vs. 14.8 Ϯ 4.0 g, P Ͻ 0.01), and adipose cell size were observed in SFR treated with glycine compared with SFR without treatment. Total NEFA concentration in the plasma of SFR was significantly decreased by glycine intake (0.64 Ϯ 0.08 vs. 1.11 Ϯ 0.09 mM in SFR without glycine, P Ͻ 0.001). In control animals, glycine decreased glucose, TGs, and total NEFA but without reaching significance. In SFR treated with glycine, mitochondrial respiration, as an indicator of the rate of fat oxidation, showed an increase in the state IV oxidation rate of the ␤-oxidation substrates octanoic acid and palmitoyl carnitine. This suggests an enhancement of hepatic fatty acid metabolism, i.e., in their transport, activation, or ␤-oxidation. These findings imply that the protection by glycine against elevated BP might be attributed to its effect in increasing fatty acid oxidation, reducing intra-abdominal fat accumulation and circulating NEFA, which have been proposed as links between obesity and hypertension. obesity; mitochondrial oxygen uptake; fatty acid oxidation OBESITY is a significant human health problem; its incidence is reaching epidemic proportions in many Western countries (2, 31). Obesity with fat accumulation predominantly in the abdominal cavity is more frequently associated with disorders of glucose and lipid metabolism than is subcutaneous fat obesity (6, 17). It is well known that increased intra-abdominal fat accumulation is also associated with elevated circulating nonesterified fatty acids (NEFA) (33), resulting from the increased lipolytic activity in adipose tissue. High levels of circulating NEFA have been assumed to be a possible link between intra-abdominal fat accumulation and elevated blood pressure (BP) (9,34,46,49).Several factors are known to be involved in the development of intra-abdominal adiposity in both humans and animals, including genetic and environmental factors, such as excessive fat or carbohydrate intake and lack of physical exercise (8, 44). Thus several animal models of obesity have been developed to investigate the mechanism by which obesity induces hypertension, hyperinsulinemia, and insulin resistance.In our laboratory, we developed an animal model of intraabdominal fat accumulation, indu...

The use of glycine to lower high blood pressure could have a significant clinical impact in patients with the metabolic syndrome and with limited resources. On the other hand, more studies are needed to explore the beneficial effect of glycine in other models of hypertension and to investigate possible side-effects of treatment with glycine.

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Sucrose-fed rats (1) had higher intra-abdominal fat mass and plasma non-esterified fatty acids and lower testosterone levels, (2) were hypertensive, and (3) had lower plasma NO metabolites than controls. The lack of testosterone by castration of sucrose-fed rats decreased high blood pressure and circulating non-esterified fatty acids and increased NO metabolites. The administration of testosterone to castrated sucrose-fed rats restored hypertension, fat accumulation, and high-circulating non-esterified fatty acids, and lowered NO metabolite levels whereas estradiol treatment did not significantly affect these variables in castrated animals. This study proposes that the low levels of testosterone found in sucrose-fed rats are sufficient to maintain central obesity and increased circulating non-esterified fatty acids, which contribute to the development of hypertension in sucrose-fed rats by modulating the biosynthesis of NO.

Insulin-elicited endothelin release in hypertriglyceridemic, hypertensive, hyperinsulinemic (HTG) rats was shown. Weanling male Wistar rats were given 30% sucrose in their drinking water for 20–24 wk. In vitro contractions of aorta and femoral arteries were elicited with 40 mM KCl. Endothelin release induced with KCl plus 50 μU/ml insulin resulted in increases in contractile responses: 41 ± 5.9 and 57 ± 6% for control and 65.5 ± 6 and 95 ± 9% for HTG aortas and femoral arteries, respectively. The endothelin ETB-receptor blocker BQ-788 decreased responses to KCl + insulin by 39 ± 8 and 53 ± 5% in control and 48 ± 13 and 79 ± 3.5% in HTG aortas and femoral arteries, respectively. The ETA-receptor antagonist PD-151242 inhibited these responses by 12 ± 10 and 1 ± 9% in control and by 51.5 ± 9 and 58.5 ± 1% in HTG aortas and femoral arteries, respectively. These results suggest that endothelin may contribute to the hypertension in this model.