Pre-meal water consumption reduces meal energy intake in older but not younger subjects

Objective: To determine whether the consumption of water 30 minutes before an ad libitum meal reduces meal energy intake in young and older adults. Research Methods and Procedures: Healthy, non‐obese young (n = 29; age, 21 to 35 years) and older (n = 21; age, 60 to 80 years) individuals were provided with an ad libitum lunch meal on two occasions. Thirty minutes before the lunch meals, subjects were given either a water preload (WP: 375 mL, women; 500 mL, men) or no preload (NP). Energy intake at the two lunch meals was measured. Visual analog scales were used to assess changes in hunger, fullness, and thirst during the meal studies. Results: There was no significant difference in meal energy intake between conditions in the young subjects (892 + 51 vs. 913 ± 54 kcal for NP and WP, respectively; p = 0.65). However, meal energy intake after the WP was significantly reduced relative to the NP condition in the older subjects (682 + 53 vs. 624 ± 56 kcal for NP and WP, respectively; p = 0.02). This effect was caused primarily by the reduction in meal energy intake after water consumption in older men. Hunger ratings were lower and fullness ratings were higher in older compared with younger adults (p < 0.01). Fullness ratings were higher in the WP condition compared with the NP condition for all subjects (p = 0.01). No age differences in thirst were detected during the test meals. Discussion: Under acute test meal conditions, pre‐meal water consumption reduces meal energy intake in older but not younger adults. Because older adults are at increased risk for overweight and obesity, intervention studies are needed to determine whether pre‐meal water consumption is an effective long‐term weight management strategy for the aging population.     

Protein intake and energy balance

Maintaining energy balance in the context of body-weight regulation requires a multifactorial approach. Recent findings suggest that an elevated protein intake plays a key role herein, through (i) increased satiety related to increased diet-induced thermogenesis, (ii) its effect on thermogenesis, (iii) body composition, and (iv) decreased energy-efficiency, all of which are related to protein metabolism. Supported by these mechanisms, relatively larger weight loss and subsquent stronger body-weight maintenance have been observed. Elevated thermogenesis and GLP-1 appear to play a role in high protein induced satiety. Moreover, a negative fat-balance and positive protein-balance is shown in the short-term, whereby fat-oxidation is increased. Furthermore, a high protein diet shows a reduced energy efficiency related to the body-composition of the body-weight regained, i.e. favor of fat free mass. Since protein intake is studied under various energy balances, absolute and relative protein intake needs to be discriminated. In absolute grams, a normal protein diet becomes a relatively high protein diet in negative energy balance and at weight maintenance. Therefore 'high protein negative energy balance diets' aim to keep the grams of proteins ingested at the same level as consumed at energy balance, despite lower energy intakes.     

Gastric bypass reduces fat intake and preference

Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation.     

Effects of dietary protein to carbohydrate balance on energy intake,fat storage,and heat production in mice

Objective:

Protein leverage plays a role in driving increased energy intakes that may promote weight gain. The influence of the protein to carbohydrate ratio (P:C) in diets of C57BL/6J mice on total energy intake, fat storage, and thermogenesis was investigated.

Design and Methods:

Male mice (9 weeks old) were provided ad libitum access to one of five isocaloric diets that differed in P:C. Food intake was recorded for 12 weeks. After 16 weeks, white adipose tissue (WAT) and brown adipose tissue (BAT) deposits were dissected, weighed, and the expression levels of key metabolic regulators were determined in BAT. In a separate cohort, body surface temperature was measured in response to 25 diets differing in protein, fat, and carbohydrate content.

Results:

Mice on low P:C diets (9:72 and 17:64) had greater total energy intake and increased WAT and BAT stores. Body surface temperature increased with total energy intake and with protein, fat, and carbohydrate, making similar contributions per kJ ingested. Expression of three key regulators of thermogenesis were downregulated in BAT in mice on the lowest P:C diet.

Conclusions:

Low‐protein diets induced sustained hyperphagia and a generalized expansion of fat stores. Increased body surface temperature on low P:C diets was consistent with diet‐induced thermogenesis (DIT) as a means to dissipate excess ingested energy on such diets, although this was not sufficient to prevent development of increased adiposity. Whether BAT was involved in DIT is not clear. Increased BAT mass on low P:C diets might suggest so, but patterns of thermogenic gene expression do not support a role for BAT in DIT, although they might reflect failure of thermogenic function with prolonged exposure to a low P:C diet.     

Effects of increased meal frequency on fat oxidation and perceived hunger

Objective:

Consuming smaller, more frequent meals is often advocated as a means of controlling body weight, but studies demonstrating a mechanistic effect of this practice on factors associated with body weight regulation are lacking. The purpose of this study was to compare the effect of consuming three (3M) vs. six meals (6M) per day on 24‐h fat oxidation and subjective ratings of hunger.

Design and Methods:

Lean (body mass index <25 kg/m²) subjects (7M, 8F) were studied in a whole‐room calorimeter on two occasions in a randomized cross‐over design. Subjects were provided isoenergetic, energy balanced diets with a 1‐ to 2‐week washout between conditions. Hunger, fullness, and “desire to eat” ratings were assessed throughout the day using visual analog scales and quantified as area under the curve (AUC).

Results:

There were no differences (P < 0.05) in 24‐h energy expenditure (8.7 ± 0.3 vs. 8.6 ± 0.3 mj d^?1), 24‐h respiratory quotient (0.85 ± 0.01 vs. 0.85 ± 0.01), or 24‐h fat oxidation (82 ± 6 vs. 80 ± 7 g day^‐1) between 3M and 6M, respectively. There was no difference in fullness 24‐h AUC, but hunger AUC (41850 ± 2255 vs. 36612 ± 2556 mm.24 h, P = 0.03) and “desire to eat” AUC (47061 ± 1791 vs. 41170 ± 2574 mm.24 h, P = 0.03) were greater during 6M than 3M.

Conclusion:

We conclude that increasing meal frequency from three to six per day has no significant effect on 24‐h fat oxidation, but may increase hunger and the desire to eat.

     

Effect of a high fat intake on protein utilization during ontogenetic development

Male rats (Wistar strain, Velaz, Prague) aged 30, 90 and 150 days were fed 14 days ad libitum on a high fat diet (containing 40% margarine) and their growth (PER, NPR) and utilization (NPU, LPU) parameters of protein (casein) biological value were compared with those of animals given a standard gel containing 10% margarine (the diets were isoenergetic). The course of gluconeogenesis in their liver was also determined by measuring phosphoenolpyruvate carboxykinase (PEPCK) activity. A high fat intake had a negative effect on the growth parameters of protein biological value, PER and NPR, in all three age groups and on the utilization parameters NPU and LPU in 30- and 90-day-old rats. The nonsignificant increase in NPU and LPU in the oldest animals was evidently related to the equal protein intake compared with the control, indicating that proteins need to be utilized more economically in the presence of a raised fat intake; owing to their far lower fat intake compared with 90-day-old animals on a high fat diet, the fat had a less negative effect on their protein utilization than in the younger age group. The negative effect of a high fat intake was confirmed by high activation of gluconeogenesis in 30- and 90-day-old animals and by raised phosphoenolpyruvate carboxykinase activity in 150-day-old rats, in which the supposition that gluconeogenesis would be highly activated if the diet were administered for a period other than 14 days cannot be ignored. The biological and biochemical methods employed in this study can be used with a wider perceptual range of dietary nutrients to determine optimum nutrient values under different conditions.     

Ghrelin and the regulation of food intake and energy balance

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is synthesized principally in the stomach and is released in response to acute and chronic changes in nutritional state. In addition to having a powerful effect on the secretion of growth hormone, ghrelin stimulates food intake and transduces signals to hypothalamic regulatory nuclei that control energy homeostasis. Thus, it is interesting to note that the stomach may play an important role in not only digestion but also pituitary growth hormone release and central feeding regulation. We summarize recent findings on the integration of ghrelin into neuroendocrine networks that regulate food intake and energy balance.     

Increased resting energy expenditure, fat oxidation, and food intake in patients with highly active antiretroviral therapy-associated lipodystrophy

Highly active antiretroviral therapy (HAART) is associated with metabolic adverse events such as lipodystrophy in human immunodeficiency virus (HIV)-infected patients. The objective of the present study was to evaluate the effects of HAART-associated lipodystrophy on resting energy expenditure and caloric intake. In this cross-sectional study we compared resting energy expenditure (REE) and energy intake in 30 HAART-treated patients with lipodystrophy (HAART+LD+) with 13 HAART-treated patients without lipodystrophy (HAART+LD-). REE was measured using indirect calorimetry, and energy intake was recorded as a 3-day diary of food intake. REE (5,180+/-160 vs. 4,260+/-150 J/min, P<0.01) and also REE expressed per fat-free mass (86+/-1 vs. 78+/-2 J.kg fat-free mass-1.min-1, P<0.01) were significantly higher in the HAART+LD+ than the HAART+LD- group. Rate of lipid oxidation was significantly higher in the HAART+LD+ than the HAART+LD- group. Total energy and fat intakes were significantly increased in the HAART+LD+ compared with the HAART+LD- group. These results imply that HAART-associated lipodystrophy is associated with increased REE and lipid oxidation and with increased caloric and fat intake.     

CD36 gene deletion reduces fat preference and intake but not post-oral fat conditioning in mice

Several findings suggest the existence of a "fatty" taste, and the CD36 fatty acid translocase is a candidate taste receptor. The present study compared fat preference and acceptance in CD36 knockout (KO) and wild-type (WT) mice using nutritive (triglyceride and fatty acid) and nonnutritive (Sefa Soyate oil) emulsions. In two-bottle tests (24 h/day) naive KO mice, unlike WT mice, displayed little or no preference for dilute soybean oil, linoleic acid, or Sefa Soyate emulsions. At high concentrations (2.5-20%), KO mice developed significant soybean oil preferences, although they consumed less oil than WT mice. The postoral actions of fat likely conditioned these preferences. KO mice, like WT mice, learned to prefer a flavored solution paired with intragastric soybean oil infusions. These findings support CD36 mediation of a gustatory component to fat preference but demonstrate that it is not essential for fat-conditioned flavor preferences. The finding that oil-naive KO mice failed to prefer a nonnutritive oil, assumed to provide texture rather than taste cues, requires explanation. Finally, CD36 deletion decreased fat consumption and enhanced the ability of the mice to compensate for the calories provided by their optional fat intake.     

Heparanase affects food intake and regulates energy balance in mice

Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.     

Effects of two weeks' mandatory snack consumption on energy intake and energy balance

Objective: Our goal was to compare the effects of mandatory consumption of commercial snack products (CSPs) on energy intakes and energy balance in free‐living adults and to assess the interaction between habitual level of CSP consumption and the interventions. Research Methods and Procedures: Four groups of 18 subjects (lean and overweight, males and females) were studied using a crossover design. Subjects consumed one type of CSP (high‐carbohydrate, high‐fat, or mixed composition) at three manipulations of energy 0 MJ (control), 1.5 MJ (low‐energy), and 3.0 MJ (high‐energy) each day during three 14‐day interventions. The study design was parallel for type of CSP (macronutrient composition) and within‐subjects for energy level. Subjects self‐recorded food intakes between Days 8 and 14, and body weights were investigator‐recorded on Days 1, 8, and 15 of each intervention period. Daily energy expenditure was estimated by heart rate monitoring. Results: Daily energy intakes increased from 10.4 MJ (control) to 11.1 MJ (low‐energy) and 11.5 MJ (high‐energy) (p < 0.001), resulting in a trend (not significant) for body weight gain. Energy balance was more positive when subjects were not recording their food intakes than when they were (p < 0.001). There was a trend (not significant) for greater increases in energy intake with increasing fat content, and energy density, of the interventions. Frequent CSP consumers compensated more for the interventions than did infrequent CSP consumers (R² = 0.125, p = 0.003). Discussion: Subjects partially compensated for energy when supplemented with CSPs over 14‐day periods, although this was insufficient to prevent some increase in energy balance. The level of compensation correlated with habitual energy intake from CSPs.     

Intracerebroventricular C75 decreases meal frequency and reduces AgRP gene expression in rats

3-Carboxy-4-alkyl-2-methylenebutyrolactone (C75), an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyltransferase-1, reduces food intake and body weight in rodents when given systemically or centrally. Intracellular molecular mechanisms involving changes in cellular energy status are proposed to initiate the feeding and body weight reductions. However, effectors that lie downstream of these initial steps are not yet fully identified. Present experiments characterize the time courses of hypophagia and weight loss after single injections of C75 into the lateral cerebroventicle in rats and go on to identify specific meal pattern changes and coinciding alterations in gene expression for feeding-related hypothalamic neuropeptides. C75 reduced chow intake and body weight dose dependently. Although the principal effects occurred on the first day, weight losses relative to vehicle control were maintained over multiple days. C75 did not affect generalized locomotor activity. C75 began to reduce feeding after a 6-h delay. The hypophagia was due primarily to decreased meal number during 6-12 h without a significant effect on meal size, suggesting that central C75 reduced the drive to initiate meals. C75 prevented the anticipated hypophagia-induced increases in mRNA for AgRP in the arcuate nucleus at 22 h and at 6 h when C75 begins to suppress feeding. Overall, the data suggest that gene expression changes leading to altered melanocortin signaling are important for the hypophagic response to intracerebroventricular C75.     

Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance

Macroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over cellular components. Here we demonstrate a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in the regulation of food intake and energy balance. We show that starvation-induced hypothalamic autophagy mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which in turn regulate AgRP levels. The functional consequences of inhibiting autophagy are the failure to upregulate AgRP in response to starvation, and constitutive increases in hypothalamic levels of pro-opiomelanocortin and its cleavage product α-melanocyte-stimulating hormone that typically contribute to a lean phenotype. We propose a conceptual framework for considering how autophagy-regulated lipid metabolism within hypothalamic neurons may modulate neuropeptide levels to have immediate effects on food intake, as well as long-term effects on energy homeostasis. Regulation of hypothalamic autophagy could become an effective intervention in conditions such as obesity and the metabolic syndrome.     

Increased calcium intake reduces plasma cholesterol and improves vasorelaxation in experimental renal failure

Chronic renal failure (CRF) is associated with abnormal lipid metabolism and high prevalence of vascular complications. Calcium salts are commonly used in CRF as phosphate binders. Increased calcium intake may also lower plasma cholesterol and beneficially influence vascular tone. Therefore, we investigated the influence of increasing dietary calcium from 0.3% to 3.0% for 8 wk after 5/6 nephrectomy (NTX) on plasma cholesterol and mesenteric resistance vessel tone in male Sprague-Dawley rats. The groups were Sham, Sham-Calcium, NTX, and NTX-Calcium (n = 10-11). Blood pressure was modestly elevated after NTX, whereas the plasma creatinine, urea nitrogen, phosphate, and parathyroid hormone levels were clearly increased. The high-calcium diet suppressed plasma phosphate and parathyroid hormone but was without effect on blood pressure. The NTX resulted in 1.6-fold elevation in plasma total cholesterol and 40% reduction in high density-to-low density lipoprotein ratio (HDL/LDL). However, the lipid profile in NTX rats on the high-calcium diet did not differ from sham-operated controls. The endothelium-mediated relaxations induced by acetylcholine were impaired in NTX rats, whereas the response was normalized by a high-calcium diet. No differences in vasorelaxations by the endothelium-independent vasodilator nitroprusside were detected. In conclusion, improved vasorelaxation after a high-calcium diet could be due to reduced plasma total cholesterol and ameliorated HDL/LDL ratio, although decreased plasma phosphate and parathyroid hormone may also play a significant role in the vascular effects of increased calcium intake.     

Increased expression of LDL receptor-related protein 1 during human cytomegalovirus infection reduces virion cholesterol and infectivity

In response to virus infection, cells can alter protein expression to modify cellular functions and limit viral replication. To examine host protein expression during infection with human cytomegalovirus (HCMV), an enveloped DNA virus, we performed a semiquantitative, temporal analysis of the cell surface proteome in infected fibroblasts. We determined that resident low density lipoprotein related receptor 1 (LRP1), a plasma membrane receptor that regulates lipid metabolism, is elevated early after HCMV infection, resulting in decreased intracellular cholesterol. siRNA knockdown or antibody-mediated inhibition of LRP1 increased intracellular cholesterol and concomitantly increased the infectious virus yield. Virions produced under these conditions contained elevated cholesterol, resulting in increased infectivity. Depleting cholesterol from virions reduced their infectivity by blocking fusion of the virion envelope with the cell membrane. Thus, LRP1 restricts HCMV infectivity by controlling the availability of cholesterol for the virion envelope, and increased LRP1 expression is likely a defense response to infection.     

Salmon calcitonin reduces food intake through changes in meal sizes in male rhesus monkeys

Amylinergic mechanisms are believed to be involved in the control of appetite. This study examined the effects of the amylin agonist, salmon calcitonin, on food intake and meal patterns in adult male rhesus monkeys. Fifteen minutes before the onset of their 6-h daily feeding period, monkeys received intramuscular injections of various doses of salmon calcitonin (0.032, 0.056, 0.1, 0.32, and 1 microg/kg) or saline. Salmon calcitonin dose dependently reduced total daily and hourly food intake, with significant decreases at the 0.1, 0.32, and 1 microg/kg doses. Daily food intake was reduced by approximately 35%, 62%, and 96%, at these doses, respectively. An analysis of meal patterns revealed that size of the first meal was significantly reduced across the dose range of 0.056 to 1 microg/kg, while average meal size was reduced with the 0.32 and 1 microg/kg doses. Meal number was only affected at the 1 microg/kg dose. Repeated 5-day administration of the 0.1 microg/kg dose resulted in a reduction in daily food intake only on injection day 2, while significant reductions in food intake were observed on all five injection days with a 0.32 microg/kg dose. Daily food intake was also reduced for 1 day after the termination of the 5-day injections of the 0.32 microg/kg salmon calcitonin dose. These sustained reductions in intake were expressed through decreases in meal size. These data demonstrate that salmon calcitonin acutely and consistently decreases food intake mainly through reductions in meal sizes in nonhuman primates.     

Protein intake during hemodialysis maintains a positive whole body protein balance in chronic hemodialysis patients

Protein energy malnutrition is present in 18 to 56% of hemodialysis patients. Because hemodialysis has been regarded as a catabolic event, we studied whether consumption of a protein- and energy-enriched meal improves the whole body protein balance during dialysis in chronic hemodialysis (CHD) patients. Patients were studied on a single day between dialysis (HD- protocol) in the morning while fasting and in the afternoon while consuming six small test meals. Patients were also studied during two separate dialysis sessions (HD+ protocol). Patients were fasted during one and consumed the meals during the other. Whole body protein metabolism was studied by primed constant infusion of l-[1-(13)C]valine. During HD-, feeding changed the negative whole body protein balance observed during fasting to a positive protein balance. Dialysis deepened the negative balance during fasting, whereas feeding during dialysis induced a positive balance comparable to the HD- protocol while feeding. Plasma valine concentrations during the studies were correlated with whole body protein synthesis and inversely correlated with whole body protein breakdown. We conclude that the consumption of a protein- and energy-enriched meal by CHD patients while dialyzing can strongly improve whole body protein balance, probably because of the increased amino acid concentrations in blood.