Background-Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, that may also cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in the cachexia associated with chronic heart failure (CHF). Methods and Results-Plasma ghrelin was measured in 74 patients with CHF and 12 control subjects, together with potentially important anabolic and catabolic factors, such as GH and tumor necrosis factor (TNF-␣). Patients with CHF were divided into two groups, those with cachexia (nϭ28) and those without cachexia (nϭ46). Plasma ghrelin did not significantly differ between all CHF patients and controls (181Ϯ10 versus 140Ϯ14 fmol/mL, PϭNS). However, plasma ghrelin was significantly higher in CHF patients with cachexia than in those without cachexia (237Ϯ18 versus 147Ϯ10 fmol/mL, PϽ0.001). Circulating GH, TNF-␣, norepinephrine, and angiotensin II were also significantly higher in CHF patients with cachexia than in those without cachexia. Interestingly, plasma ghrelin correlated positively with GH (rϭ0.28, PϽ0.05) and TNF-␣ (rϭ0.31, PϽ0.05) and negatively with body mass index (rϭϪ0.35, PϽ0.01). Conclusions-Plasma ghrelin was elevated in cachectic patients with CHF, associated with increases in GH and TNF-␣ and a decrease in body mass index. Considering ghrelin-induced positive energy effects, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with CHF.

Tissue factor pathway inhibitor (TFPI), a protease inhibitor that is present in free and lipoprotein-associated forms in plasma and that also occurs as an endothelial cell-associated form, can inhibit the initial reactions of the tissue factor-mediated coagulation pathway. Although a positive correlation between plasma TFPI activity and cholesterol concentration in human plasma has been demonstrated, levels of the various forms of TFPI, ie, the LDL/VLDL-associated form, the HDL-associated form, and the free form, have not yet been completely determined in hyperlipidemia. We therefore established a method for the measurement of each of these forms of TFPI in plasma by gel filtration of plasma in buffer containing 1 mol/L NaCl. The recovery of TFPI activity in the free form was markedly greater as assessed by the new method than the recovery reported when other methods have been used. We employed the new method to analyze TFPI activity in 19 hyperlipidemic patients and compared the results with those for normal control subjects. The level of LDL/VLDL-associated TFPI in hyperlipidemic patients was significantly increased compared with control subjects' levels (0.383 +/- 0.112 versus 0.237 +/- 0.077 U/mL), whereas the level of the free form of TFPI in hyperlipidemic patients was significantly decreased (0.381 +/- 0.132 versus 0.495 +/- 0.106 U/mL), the former being positively correlated with cholesterol level, while the latter was negatively correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

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SummaryThe effects of low energy diets on protein metabolism in terms of the metabolic pool, active protein pool, and active and inactive protein synthesis rates were studied using [15N]glycine in five obese patients (percentage of ideal body weight, 120-190%). For 10 days, the patients were given a control diet containing 2,000 kcal of energy and 80g of protein. For the next 2 weeks, they were given Diet A with 1,100 kcal of energy and 70g of protein, and for the last 2 weeks given Diet B with 1,100 kcal of energy and 50g of protein. During the Diet A period , the active protein pool and the active and inactive protein synthesis rates were about the same as during the control diet period, although the metabolic pool tended to be slightly smaller than during the control diet period. During the Diet B period, the metabolic pool, active protein pool , and active protein synthesis rate were all significantly different from the values during the control diet period. The results suggest that protein metabo lism in obese patients is not maintained with less than 70g of protein daily when energy intake was restricted to 1,100 kcal/day. Key Words obese patients, protein metabolism, energy restriction, low energy diet, metabolic pool, active protein pool, inactive protein pool , active protein synthesis rate, inactive protein synthesis rate, [15N]glycine When energy is restricted, the nitrogen balance becomes lower; an increase in the protein intake under energy reductions improves the nitrogen balance (1-3). A detailed picture of this phenomenon has been made possible by using tracer amino acids, which allows estimation of the rate of body protein turnover (4-9). Garlick et al. (6) studied the nitrogen flux and protein synthesis and breakdown using 227

SummaryThe effect of nitrogen intake on nitrogen balance was studied in six obese patients receiving low energy diets. They were given a control diet containing 2,000 kcal of energy and 80g of protein for the first ten days. Then they were given Diet A with 1,100 kcal of energy and 70g of protein for the next 2 weeks, followed by Diet B with 1,100 kcal of energy and 50g of protein for 2 weeks. The relationship between nitrogen intake (X, mg/kg) and nitrogen balance (Y, mg/kg) during the low energy diet periods was statistically significant, with Y=0.388X-60.32 (SD= 17.71, r=+0.67, n=11, p<0.05). The nitrogen and protein requirements were estimated from this equation to be 201 .1mg/kg and 1.26g/kg, respectively. In our experiment, the nitrogen balance in obese patients was well maintained although total energy was reduced to 1,100 kcal/day in Diet A. It is suggested that protein quantity in the diets should be taken into account when a low energy diet is used for the treatment of obesity . Key Words obese patients, protein metabolism, energy restriction , low energy diet, nitrogen balance, maintenance requirement (for equilibrium) , protein requirementIn humans, the protein content of energy-restricted diets greatly influences the protein metabolism of the whole body (1-7). A protein-sparing modified fast (2-6) has been used in adults as a method for weight reduction wherein nitrogen balance is maintained. Garlick et al.(1) studied the nitrogen flux, protein synthesis, and breakdown using [15N]glycine in obese subjects eating an energy-restricted diet with various protein levels. They found that if protein intake was adequate (50 g/day), whole-body protein synthesis was unchanged when the energy intake was decreased 219