Effect of temperature and/or sweetness of beverages on body composition in rats.

Sweetened beverages are mainly consumed cold and various processes are activated in response to external temperature variations. However, the effect of internal temperature variations through the ingestion of cold beverages is far from clear. Two experiments were conducted to investigate the effect of beverage temperature on body composition. Sprague-Dawley rats (5-6-week-old males) had free access to food and beverage for 8 weeks. Energy intake, body weight and body composition were monitored. In Expt 1, two groups of rats (n 9) consumed water at room temperature (NW about 22°C) or cold (CW about 4°C). In Expt 2, rats were offered room-temperature (N) or cold (C) sweetened water (10 % sucrose CSu (n 7) and NSu (n 8); or 0·05 % acesulfame K CAk (n 6) and NAk (n 8)) for 12 h, followed by plain water. Our results show that in Expt 1, CW had higher lean body mass (P < 0·001) and lower body fat gain (P = 0·004) as compared with NW. In Expt 2, body weight (P = 0·013) and fat (P ≤ 0·001) gains were higher in the non-energetic sweetened groups, while lean body mass was not affected by the type of sweeteners or temperature. In conclusion, cold water ingestion improved lean body mass gain and decreased fat gain because of increased energy expenditure, while non-energetic sweetener (acesulfame K) increased body fat gain due to improved energy efficiency. Internal cold exposure failed to increase energy intake in contrast to that of external cold exposure.

Daily energy expenditure in rats following structured exercise training is affected by dietary phosphorus content.

P ingestion has been found to alter energy balance, while regular physical exercise (E) was reported to be associated with energy compensation. However, it is not clear whether dietary P would affect energy compensation following structured E. Two experiments were performed, low P (LP) (0·1, 0·2 and 0·3 %P) and high P (HP) (0·3 , 0·6 and 1·2 %P) diets. In each experiment, male rats were randomly divided into three groups (n 8), in which a sedentary or a moderate-intensity exercise routine (30 min 5 d a week) was implemented. Energy intake (EI); efficiency and stores; body measures and total energy expenditure (TEEx) were monitored for 6 weeks. In the LP experiment, EI and weight gain were the lowest in the 0·1 and 0·2 %P as compared with the 0·3 %P. In the HP experiment, EI was highest in the high P (0·6 and 1·2 %P) groups, while weight gain was reduced. In both experiments, exercise was able to reduce body fat accumulation and to maintain a higher % lean body mass. In the LP diets experiment, the similarity in TEEx between the sedentary and exercising groups suggests the probability of a reduction in normal daily activities, which indicates the presence of compensation for the energy expended during exercise by a subsequent reduction in EE. In contrast, the elevated TEEx in the HP exercising groups (0·6 and 1·2 %P) argue against the presence of energy compensation. In conclusion, high dietary P decreases the body's capability to compensate for the energy deficit induced by E, consequently maintaining an elevated TEEx.

Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical trial.

BACKGROUND: Phosphorus status is inversely correlated with body weight; however, the effect of phosphorus supplementation on body weight in a controlled design has not been studied. METHODS: This is a double-blind, randomized, placebo-controlled trial of 63 adults aged 18-45 years with a body mass index (BMI) of ⩾25 kg m(-2) and normal kidney function at the American University of Beirut. Participants were randomly assigned to the placebo or phosphorus group where daily placebo or phosphorus supplements were ingested with three main meals (breakfast, lunch and dinner) for a period of 12 weeks. Primary outcomes were changes in anthropometric measures, blood metabolites (including lipid profile, glucose and insulin) and subjective appetite scores. The trial is registered with Clinical Trial.gov, NCT02329990. RESULTS: Body weight was significantly lower in the phosphorus group when compared with the placebo group (-0.65 kg (95% confidence interval (CI) -1.69 to 0.40) vs 1.13 kg (95% CI 0.19 to 2.06), P=0.01). Similarly, BMI and waist circumference were significantly lower in the phosphorus group when compared with the placebo group (-0.24 kg m(-2) (95% CI -0.59 to 0.12) vs 0.42 kg m(-2) (95% CI 0.05 to 0.78), P=0.01; -3.62 cm (95% CI-4.90 to -2.33) vs 0.38 cm ( 95% CI-0.44 to 1.20), P<0.001; respectively). Several parameters of subjective appetite scores were decreased in the phosphorus-supplemented group. CONCLUSIONS: Phosphorus supplementation for 12 weeks significantly decreases body weight, BMI, waist circumference and subjective appetite scores. These findings support a promising role of the mineral phosphorus in the prevention and management of obesity, especially abdominal adiposity. The exact mechanisms of action and longer-term effects still need to be elucidated.

Refeeding and metabolic syndromes: two sides of the same coin.

Refeeding syndrome describes the metabolic and clinical changes attributed to aggressive rehabilitation of malnourished subjects. The metabolic changes of refeeding are related to hypophosphatemia, hypokalemia, hypomagnesemia, sodium retention and hyperglycemia, and these are believed to be mainly the result of increased insulin secretion following high carbohydrate intake. In the past few decades, increased consumption of processed food (refined cereals, oils, sugar and sweeteners, and so on) lowered the intake of several macrominerals (mainly phosphorus, potassium and magnesium). This seems to have compromised the postprandial status of these macrominerals, in a manner that mimics low grade refeeding syndrome status. At the pathophysiological level, this condition favored the development of the different components of the metabolic syndrome. Thus, it is reasonable to postulate that metabolic syndrome is the result of long term exposure to a mild refeeding syndrome.

Low phosphorus status might contribute to the onset of obesity.

Overweight and obesity are becoming global health problems. Although genetics certainly plays a role, weight gain is ultimately the result of a failure in the balance between energy expenditure and energy intake. Obesity during the past few decades was paralleled with several changes in dietary habits favouring low phosphorus consumption. This is believed to compromise adenosine triphosphate (ATP) production that is involved in the regulation of energy metabolism. Ingestion of high-carbohydrate-low phosphorus food is known to increase insulin release, to simultaneously stimulate peripheral uptake of phosphorus and the phosphorylation of many compounds. This creates a competition for phosphorus that compromises its availability for ATP production, possibly translated into low diet-induced thermogenesis. Moreover, reduced hepatic ATP production is believed to be transmitted through neural afferents to the central nervous system, resulting in an increase in food intake. On the other hand, the positive relation between phosphorus and red blood cell 2,3-diphosphoglycerate, which reduces oxygen affinity to haemoglobin, would be expected to reduce the capacity for physical activity. In line with that, plasma phosphorus status was reported to be inversely related to body weight. Adequate intakes of phosphorus are thus potentially protective against rising obesity epidemic across the globe.

Increased phosphorus content of preload suppresses ad libitum energy intake at subsequent meal.

Food intake is believed to be partially controlled by hepatic signals related to adenosine triphosphate (ATP) status. We hypothesized that increased phosphorus content of one meal can stimulate hepatic ATP synthesis of the next meal, which in turn contributes to satiation. This hypothesis was tested by measuring the energy intake after phosphorus addition to several preloads. The phosphorus content of the different preloads was found to be inversely related to the energy intake at a subsequent meal, although the exact mechanism behind such effects was not studied. Such findings point to a potential role for phosphorus in the control of food intake.

Plasma taurine and cysteine levels following an oral methionine load: relationship with coronary heart disease.

OBJECTIVE: To test the hypothesis that endogenous synthesis of taurine from methionine is impaired in people with coronary heart disease (CHD). DESIGN: Nested case-control. SUBJECTS: Indian Asian and white European males aged 35-60 y. Both racial group included patients with CHD and healthy controls. Samples from 20 subjects in each of the four groups were selected at random. INTERVENTION: Fasting blood samples were taken before and 6 h after consumption of methionine (100 mg/kg body weight) MEASUREMENTS: Plasma concentrations of taurine, cysteine, pyridoxal-5-phosphate and 4-pyridoxic acid. RESULTS: Fasting plasma taurine values were higher in Indian Asian cases than controls, but not significantly different between European cases and controls. Postload taurine values were higher in cases than controls in both racial groups (P=0.002). Fasting plasma cysteine was higher in cases than controls (P=0.002) and higher in Indian Asians than Europeans (0.007), but there were no significant differences between any of the groups in postload cysteine values, nor in plasma pyridoxal-5-phosphate or 4-pyridoxic acid. CONCLUSIONS: Taurine production from methionine was not impaired in patients with CHD, but fasting plasma cysteine was higher in CHD cases than controls.

Should the food intake of patients admitted to acute hospital services be routinely supplemented? A randomized placebo controlled trial.

BACKGROUND: Many patients admitted to acute hospital services are underweight or harbour vitamin deficiencies. OBJECTIVES: To determine the effect on patient throughput of a policy of routine vitamin supplementation, and of early routine sipfeed supplementation in 'thin' patients (5-10% weight loss or body mass index 18-22). DESIGN: Factorial randomized placebo controlled trial of oral multivitamins from the first day of admission, and, after nutritional screening, of a nutritionally complete sipfeed from the second day in 'thin' patients. SETTING: Acute medical, surgical and orthopaedic hospital services of a London teaching hospital. PARTICIPANTS: 1561 patients admitted as emergencies were included in the vitamin study of which 549 were included in the sipfeed study. MAIN OUTCOME MEASURE: Length of hospital stay (LOS). RESULTS: Offering multivitamins to acute admissions resulted in a mean change (reduction) in LOS of -0.4 days 95% CI (-2-1.2days). The results suggest greater reductions for those discharged after 10 days: mean change=-2.3 days 95% CI (-5.7 to 1.2). Sipfeed supplementation was associated with an increased mean length of stay 2.8 days 95% CI (-0.8-6.3). 18% of acute admissions were classified undernourished on the basis of BMI, MUAC or percent weight loss combined. CONCLUSIONS: No benefit was observed for sipfeed intervention although a small benefit of less than one day is not excluded. Vitamin supplementation may have slight but economically important benefit.

Methylenetetrahydrofolate reductase 677 C-->T mutation and coronary heart disease risk in UK Indian Asians.

Plasma homocysteine concentrations are elevated in UK Indian Asians and may contribute to twice as many coronary heart disease (CHD) deaths in this group compared with European whites. The mechanisms underlying elevated homocysteine concentrations among Indian Asians are not well understood. In this study, we have investigated the extent to which the methylenetetrahydrofolate reductase (MTHFR) 677 C-->T mutation accounts for elevated plasma homocysteine and increased CHD risk in Indian Asians compared with European whites. We investigated 454 male cases (with myocardial infarction or angiographically proven CHD: 224 Indian Asians, 230 European whites) and 805 healthy male controls (381 Indian Asians, 424 European whites). Fasting homocysteine concentrations, MTHFR 677 C-->T genotype, and conventional CHD risk factors were measured. The prevalence of homozygous MTHFR 677T in Indian Asian controls was less than one third that in European white controls (3.1% versus 9. 7%, P<0.001). In Indian Asians, the TT MTHFR genotype was not associated with homocysteine concentrations and was not present in any of the Asian controls with hyperhomocysteinemia (>15 micromol/L). In contrast, among European whites, the TT MTHFR genotype was strongly related to elevated plasma homocysteine concentrations and was found in 27% of the European controls with hyperhomocysteinemia. Elevated homocysteine in Indian Asian compared with European white controls was accounted for by their reduced levels of B vitamins but not by the MTHFR 677T genotype. However, neither the TT MTHFR genotype nor B vitamin levels explained the elevated homocysteine concentrations in CHD cases compared with controls. TT MTHFR was not a risk factor for early-onset CHD in Indian Asians (odds ratio, 0.5; 95% confidence interval, 0.1 to 2.4; P=0.39), unlike in European whites (odds ratio, 2.1; 95% confidence interval, 1.1 to 4. 1; P=0.02). We conclude that the MTHFR 677T: mutation does not contribute to elevated plasma homocysteine concentrations or increased CHD risk in Indian Asians compared with European whites. Our results suggest that novel genetic defects and/or environmental factors influence homocysteine metabolism in Indian Asians residing in the United Kingdom.

Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for coronary heart disease (CHD). Dietary supplementation with B vitamins lowers plasma homocysteine by up to 30%. However, little is known about the potential beneficial effects of homocysteine lowering on vascular function in patients with CHD. METHODS AND RESULTS: We investigated 89 men with CHD (aged 56 [range 39 to 67] years). Brachial artery flow-mediated dilatation (endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured before and 8 weeks after treatment with either (1) folic acid (5 mg) and vitamin B(12) (1 mg) daily (n=59) or (2) placebo (n=30). Total, protein-bound, and free plasma homocysteine, serum folate, and vitamin B(12) were measured at baseline and at 8 weeks. Flow-mediated dilatation improved after treatment with B vitamins (2.5+/-3.2% to 4.0+/-3.7%, P:=0.002) but not placebo (2.3+/-2.6% to 1.9+/-2.6%, P:=0.5). Vitamin therapy lowered plasma concentrations of total homocysteine (from 13.0+/-3.4 to 9.3+/-1.9 micromol/L, P:<0.001), protein-bound homocysteine (from 8.7+/-2.8 to 6.2+/-1.4 micromol/L, P:<0.001), and free homocysteine (from 4.3+/-1.2 to 3.0+/-0.6 micromol/L, P:<0.001) and raised concentrations of serum folate (from 10.3+/-4.3 to 31.2+/-10.8 ng/mL, P:<0.001) and vitamin B(12) (from 314+/-102 to 661+/-297 pg/mL, P:<0.001). In regression analysis, improved flow-mediated dilatation correlated closely with the reduction in free plasma homocysteine (r=-0.26, P:=0.001), independent of changes in protein-bound homocysteine, folate, and vitamin B(12). Nitroglycerin-induced dilatation was unchanged after both B vitamins and placebo. CONCLUSIONS: Folic acid and vitamin B(12) supplementation improves vascular endothelial function in patients with CHD, and this effect is likely to be mediated through reduced concentrations of free plasma homocysteine concentrations. Our data support the view that lowering homocysteine, through B vitamin supplementation, may reduce cardiovascular risk.

The postprandial rates of glycogen and lipid synthesis of lean and obese female Zucker rats.

OBJECTIVE: To determine the relative rates of glycogenesis and lipogenesis following administration of a test meal in lean and obese Zucker rats. PROTOCOL: Nine-week-old lean and obese Zucker rats were fasted overnight, then tube-fed a test meal of balanced composition amounting to 16kJ (lean rats and one group of obese rats) or 24kJ (one group of obese rats) and containing 200 mg 1-(13)C glucose. Immediately after the meal the rats were injected intraperitoneally with 5 mCi of 3H2O and killed 1 h later. METHODS: Glycogenesis was calculated from the incorporation of 3H into liver glycogen divided by the specific activity of plasma water. Lipogenesis was calculated similarly from the incorporation of 3H into saponifiable lipids in liver and perirenal adipose tissue. The proportion of glycogen synthesized by the indirect pathway via pyruvate was determined from the ratio of 3H labelling at positions C6 and C2 in the glycogen glucose residues. Glycogen synthesis from glucose was determined from the ratio of 13C enrichment in liver glycogen to that in plasma glucose. RESULTS: The rate of synthesis of glycogen was considerably lower in the livers of obese rats than those of lean controls, with the larger meal causing a small but significant increase in glycogenesis. The proportion of glycogen synthesized via pyruvate showed a non-significant increase in the obese rats, while the amount of glycogen synthesized from glucose was significantly decreased. Hepatic lipogenic rates were about five times higher in both groups of obese rats than the lean controls. In adipose tissue, lipogenesis per g tissue was slightly reduced in the obese rats, although there was clearly an increase in adipose tissue lipogenic activity per whole animal. The larger meal caused a greater rise in plasma glucose and insulin concentrations but did not affect lipogenic rates, although it did cause a greater suppression of lipolysis, as indicated by a lower plasma glycerol concentration. CONCLUSION: Ingested carbohydrate is partitioned predominantly into hepatic fatty acid synthesis in obese Zucker rats. Hepatic glycogen synthesis is suppressed and comes mainly from precursors other than glucose. The suppression of hepatic glycogen synthesis may contribute to the increased energetic efficiency of obese Zucker rats.

Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asian and European men.

BACKGROUND: Reasons for the increase in mortality due to coronary heart disease (CHD) in UK Indian Asians are not well understood. In this study, we tested the hypotheses that elevated plasma homocysteine concentrations are a risk factor for CHD in Indian Asians, and explain part of their increased CHD risk, compared with Europeans. METHODS: We undertook two parallel case-control studies, one in Europeans and one in Indian Asians. We recruited 551 male cases (294 European, 257 Indian Asian) and 1025 healthy male controls (507 European, 518 Indian Asian). Fasting and post-methionine load homocysteine, vitamin B12 and folate concentrations, and conventional CHD risk factors were measured. FINDINGS: Fasting homocysteine concentrations were 8% higher (95% CI 3-14) in cases compared with controls, in both ethnic groups. The odds ratio of CHD for a 5 micromol/L increment in fasting plasma homocysteine was 1.3 (1.1-1.6) in Europeans and 1.2 (1.0-1.4) in Indian Asians. The association between fasting plasma homocysteine and CHD was independent of conventional CHD risk factors in both ethnic groups. Post-load homocysteine concentrations were not significantly different in cases compared with controls. Among the controls, fasting homocysteine concentrations were 6% (2-10) higher in Indian Asians than in Europeans. From the results we estimate that elevated homocysteine may contribute to twice as many CHD deaths in Indian Asians, compared with Europeans. The differences in homocysteine concentrations between the two ethnic groups were explained by lower vitamin B12 and folate levels in Asians. INTERPRETATION: Plasma homocysteine is a novel and independent risk factor for CHD in Indian Asians, and may contribute to their increased CHD risk. Raised homocysteine concentrations in Indian Asians may be related to their reduced vitamin B12 and folate levels, implying that the increased CHD risk in this group may be reduced by dietary vitamin supplementation.

Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects.

We hypothesized that physiological increments in plasma homocysteine after low-dose oral methionine or dietary animal protein induce vascular endothelial dysfunction and that there is a graded, inverse relationship between homocysteine concentration and endothelial function. We studied 18 healthy volunteers aged 18 to 59 years. Brachial artery flow-mediated and glyceryltrinitrate-induced dilatation were measured after 1) oral L-methionine (10, 25, and 100 mg/kg), 2) dietary animal protein (lean chicken 551+/-30 g, comprising 3.2+/-0.2 g methionine), and 3) methionine-free amino acid mix (100 mg/kg). Methionine (10, 25, and 100 mg/kg) induced a dose-related increase in homocysteine (9.4+/-1.3 to 12.2+/-2.1, 17. 6+/-2.6, and 26.1+/-4.2 micromol/L, respectively; P<0.001) and a reduction in flow-mediated dilatation (4.1+/-0.8 to 2.1+/-0.8, 0. 3+/-0.8, and -0.7+/-0.8%, respectively; P<0.001) at 4 hours. Compared with usual meal, animal protein increased plasma homocysteine (9.6+/-0.8 to 11.2+/-0.9 micromol/L, P=0.005) and reduced flow-mediated dilatation (4.5+/-0.7% to 0.9+/-0.6%, P=0.003). Methionine-free amino acid mix did not induce any changes. Glyceryltrinitrate-induced dilatation was unchanged throughout. In this study, small physiological increments in plasma homocysteine after low-dose methionine and dietary animal protein induced vascular endothelial dysfunction. We propose that protein intake-induced increments in plasma homocysteine may have deleterious effects on vascular function and contribute to the development and progression of atherosclerosis.

The thiamin, riboflavin and pyridoxine status of patients on emergency admission to hospital.

The aim of this study was to assess the prevalence of thiamin, riboflavin and pyridoxine deficiencies at admission to an acute hospital. One hundred and twenty adult patients were selected at random from those admitted via the Accident and Emergency department over 3 days. Comparisons were made with a group of 80 healthy blood donors sequentially attending a local transfusion centre. The alcohol intake of 500 patients admitted sequentially via the same Accident and Emergency department was also assessed. Erythrocyte transketolase (ETK), glutathione reductase (EGR) and aspartate aminotransferase (EAA) coenzyme activation assays were used to determine thiamin, riboflavin and pyridoxine deficiencies. The prevalences of deficiency states in the inpatient group were 21, 2.7 and 32% for thiamin, riboflavin and pyridoxine deficiencies respectively with 49.2% being deficient in one or more vitamin. The mean alcohol intake in the group of patients in whom this was assessed was 9.7 units per week compared with 10 units per week amongst blood donors.

Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy.

BACKGROUND: Hyperhomocysteinemia is a major and independent risk factor for vascular disease. The mechanisms by which homocysteine promotes atherosclerosis are not well understood. We hypothesized that elevated homocysteine concentrations are associated with rapid onset endothelial dysfunction, which is mediated through oxidant stress mechanisms and can be inhibited by the antioxidant vitamin C. METHODS AND RESULTS: We studied 17 healthy volunteers (10 male and 7 female) aged 33 (range 21 to 59) years. Brachial artery diameter responses to hyperemic flow (endothelium dependent), and glyceryltrinitrate (GTN, endothelium independent) were measured with high resolution ultrasound at 0 hours (fasting), 2 hours, and 4 hours after (1) oral methionine (L-methionine 100 mg/kg), (2) oral methionine preceded by vitamin C (1g/day, for 1 week), and (3) placebo, on separate days and in random order. Plasma homocysteine increased (0 hours, 12.8+/-1.4; 2 hours, 25.4+/-2.5; and 4 hours, 31. 2+/-3.1 micromol/l, P<0.001), and flow-mediated dilatation fell (0 hours, 4.3+/-0.7; 2 hours, 1.1+/-0.9; and 4 hours, -0.7+/-0.8%) after oral L-methionine. There was an inverse linear relationship between homocysteine concentration and flow-mediated dilatation (P<0. 001). Pretreatment with vitamin C did not affect the rise in homocysteine concentrations after methionine (0 hours, 13.6+/-1.6; 2 hours, 28.3+/-2.9; and 4 hours, 33.8+/-3.7 micromol/l, P=0.27), but did ameliorate the reduction in flow-mediated dilatation (0 hours, 4. 0+/-1.0; 2 hours, 3.5+/-1.2 and 4 hours, 2.8+/-0.7%, P=0.02). GTN-induced endothelium independent brachial artery dilatation was not affected after methionine or methionine preceded by vitamin C. CONCLUSIONS: We conclude that an elevation in homocysteine concentration is associated with an acute impairment of vascular endothelial function that can be prevented by pretreatment with vitamin C in healthy subjects. Our results support the hypothesis that the adverse effects of homocysteine on vascular endothelial cells are mediated through oxidative stress mechanisms.

A placebo controlled investigation of the effects of tryptophan or placebo on subjective and objective measures of fatigue.

OBJECTIVE: To examine the effect of L-tryptophan administration on subjective and objective measures of fatigue in healthy volunteers. SUBJECTS: Six healthy volunteers (4M:2F) were recruited from staff and students at the College. SETTING: Department of Human Nutrition, St. Bartholomews and the Royal London School of Medicine and Dentistry. DESIGN: Subjects were tested for central and peripheral fatigue using a visual analogue scale, flicker fusion frequency, grip strength, reaction time and wrist ergometry. In addition, plasma free tryptophan concentrations and Trp:LNAA ratio were determined. Measurements were made before, and at 1, 2, 3 and 4 h after drinking one of two test drinks. The drinks were of either caffeine free diet Coca-Cola (placebo) or caffeine free diet Coca-Cola plus L-tryptophan (30 mg/kg: active drink). Each of the six subjects was tested after placebo and active drink with a one week washout period between test days. RESULTS: Subjective fatigue was significantly increased following tryptophan compared to placebo (P < 0.002), and objective measures of central fatigue were significantly increased by tryptophan compared to placebo (flicker fusion frequency: P < 0.001; reaction time P < 0.001). No significant changes in grip strength were found following tryptophan compared to placebo, but a significant increase in ergometric work output was seen (P < 0.001). CONCLUSION: Tryptophan ingestion in the quantity 30 mg/kg leads to increased subjective and central fatigue. Increases in work output observed following tryptophan may be as a result of a reduced perception of discomfort during ergometry.

The effect of meal size on postprandial carbohydrate metabolism in normal and tumor-bearing rats.

Doubling the size of a meal causes less than a two-fold increase in the thermic effect of feeding. One possible reason for this is that larger meals may be associated with a change in the pathway of postprandial hepatic glycogen synthesis from the indirect pathway, involving gluconeogenesis, to the more energetically efficient direct pathway. We have therefore investigated the effect of meal size on the relative contributions of those two pathways both in normal rats and in tumor-bearing rats, which have previously been shown to utilize the indirect pathway to a greater extent. Rats bearing a transplantable Leydig cell tumor and freely fed controls were fasted overnight and given a test meal amounting to 12 or 24 kJ of their normal diet. They were then injected with 3H2O and 14C-glycerol and killed one hour later. The total amount of 3H incorporated into liver glycogen was not affected by meal size, although it was greater in tumor-bearing rats than controls. Analysis of the 3H labelling at different positions in the glycogen glucose residues showed that the proportion of glycogen synthesized via pyruvate, which tended to be greater in tumor-bearing rats, was significantly reduced by increasing the size of the meal. Glycogen synthesis from glycerol was not affected by either meal size or tumor growth. Increasing the size of the meal increased the rate of fatty acid synthesis in both the liver and the epididymal fat pad, but not the tumor. Thus increasing the size of the meal appeared to increase the proportion of glycogen synthesized by the direct pathway from glucose in both tumor-bearing and control animals.

Glycogen synthesis in tumor-bearing rats after ingestion of a high-glycerol meal.

Tumor-bearing rats have a high rate of postprandial hepatic glycogen synthesis by the indirect pathway that involves gluconeogenesis. This study was designed to investigate the role of glycerol as a precursor for postprandial glycogen synthesis in tumor-bearing rats. Rats bearing a Leydig cell tumor and freely fed controls were fasted overnight, then fed a 16-kJ meal with or without 50 mg of glycerol by gavage. [U-14C]glycerol (1 microCi) was also administered intragastrically, and 7 mCi of 3H2O were injected intraperitoneally. The rats were killed one hour later, and the specific activities at different positions within the glycogen glucose residues in the liver were measured. Increasing the glycerol content of the meal had no significant effect on the overall incorporation of 3H into liver glycogen or on the proportion of glycogen synthesized via pyruvate in tumor-bearing or control rats. There was no difference between tumor-bearing and control rats in the amount of glycerol incorporated into glycogen, although this was increased by the high-glycerol meal. Thus glycerol appeared to make a small contribution to postprandial glycogen synthesis in tumor-bearing and control rats.

Effect of acute acipimox administration on the rates of lipid and glycogen synthesis in cachectic tumor-bearing rats.

Increased energy expenditure in cancer cachexia may be associated with increased postprandial glycogen synthesis via an indirect pathway involving gluconeogenesis. The possible beneficial effect of acipimox, a nicotinic acid analogue that suppresses lipolysis and may also inhibit gluconeogenesis, were therefore examined. Rats bearing a transplantable Leydig cell tumor and freely fed controls were fasted overnight, then given a test meal with or without 10 mg of acipimox. The meal included 200 mg of [1-13C]glucose, and the rats were injected simultaneously with 7 mCi of 3H2O and 1 microCi of [14C]glycerol. The rats were killed one hour later. The rate of incorporation of 3H2O into hepatic glycogen was increased in the tumor-bearing rats and suppressed by acipimox. Positional analysis of the tritium incorporated into glycogen indicated that a greater proportion of the glycogen was synthesized via pyruvate in the tumor-bearing rats. Acipimox tended to reduce this proportion, although the effect was not statistically significant. Neither tumor growth nor acipimox significantly affected the proportion of 13C incorporated into different positions in the glycogen glucose. Glycogen synthesis from glycerol tended to decrease when lipolysis was suppressed by acipimox, although the statistical significance of this effect was marginal. Fatty acid synthesis in liver and adipose tissue was reduced in tumor-bearing rats, but acipimox had no effect. It is concluded that acipimox does suppress gluconeogenesis and glycogenesis in the postprandial state, but it does not normalize all the metabolic abnormalities observed in cancer cachexia.