The aim of the present study was to examine the effects of creatine supplementation on liver fat accumulation induced by a high-fat diet in rats. Rats were fed 1 of 3 different diets for 3 wk: a control liquid diet (C), a high-fat liquid diet (HF), or a high-fat liquid diet supplemented with creatine (HFC). The C and HF diets contained, respectively, 35 and 71% of energy derived from fat. Creatine supplementation involved the addition of 1% (wt:v) of creatine monohydrate to the liquid diet. The HF diet increased total liver fat concentration, liver TG, and liver TBARS and decreased the hepatic S-adenosylmethionine (SAM) concentration. Creatine supplementation normalized all of these perturbations. Creatine supplementation significantly decreased the renal activity of l-arginine:glycine amidinotransferase and plasma guanidinoacetate and prevented the decrease in hepatic SAM concentration in rats fed the HF diet. However, there was no change in either the phosphatidylcholine:phosphatidylethanolamine (PE) ratio or PE N-methyltransferase activity. The HF diet decreased mRNA for PPARα as well as 2 of its targets, carnitine palmitoyltransferase and long-chain acylCoA dehydrogenase. Creatine supplementation normalized these mRNA levels. In conclusion, creatine supplementation prevented the fatty liver induced by feeding rats a HF diet, probably by normalization of the expression of key genes of β-oxidation.

We assessed the role of the renin-angiotensin system in the response of the renal circulation to restriction of sodium intake in 38 normal patients. Both saralasin (10 to 30 ng/kg/min), an angiotensin antagonist, and SQ 20881 (30 to 300microgram/kg), a converting enzyme inhibitor, induced a dose-related increase in renal blood flow (xenon 133 washout) only when the resin-angiotension system was activated by restriction of sodium intake to 10 MEq/day. Increasing doses of saralasin (100 to 1,000 ng/kg/min) reduced renal blood flow, presumably due to the angiotensin-like action of this partial agonist. The renal vascular response to SQ 20881 paralleled the endocrine response: An identical threshold dose (30 microgram/kg) increased renal blood flow and reduced plasma angiotensin II concentration, which fell despite a progressive rise of plasma renin activity. Plasma bradykinin concentration did not change in response to SQ 20881, which also blocks kininase II. Both agents also induced a small but consistent and statistically significant reduction in arterial blood pressure, which will be important in assessing the pathogenetic significance of a blood pressure reduction in patients with hypertension. This study indicates that angiotensin mediates the renal vascular response to restriction of salt intake in normal man and provides an approach to assessing the role played by angiotensin in the pathogenesis of functional renal disease.

We assessed the role of the renin-angiotensin system in the control of aldosterone secretion in response to sodium restriction in 62 normal subjects. Both saralasin, an angiotensin II antagonist, and SQ 20881, a converting enzyme inhibitor, induced a dose-related decrease in plasma aldosterone levels when the renin-angiotensin system was activated by restriction of sodium intake. Two types of experiments were performed with saralasin. In the first set, a dose-response relationship was established 20 min after beginning infusions ranging from 0.03-1.0 microgram/kg/min. The optimal dose was 0.1 microgram/kg/min, with a reduction in aldosterone levels of -10.1 +/- 3.8 ng/dl (P less than 0.025). Higher doses induced smaller reductions in aldosterone levels. In the second set, a 3-h infusion was given. The results were qualitatively similar but the magnitude was greater (-15 +/- 4 ng/dl; P less than 0.01). The aldosterone response 20 min after administration of SQ 20881 paralleled the angiotensin II response, with the first significant decrement (-6.5 +/- 1.5 ng/dl; P less than 0.01) occurring at 0.1 mg/kg and maximum (-10 +/- 3 ng/dl) occurring at 0.3 mg/kg. Thus, both agents produced qualitatively similar changes in aldosterone secretion in sodium-restricted normal subjects. However, neither reduced sodium restricted aldosterone levels to that measured in sodium-loaded subjects because of the intrinsic limitation of each agent. Saralasin is a partial agonist. SQ 20881 induces an increase in plasma renin activity via interruption of the short feedback loop, which probably limits its action. Yet, these data do support the hypothesis that angiotensin mediates the adrenal's response to sodium restriction in normal man.