Energy Expenditure, Carbohydrate Oxidation and Appetitive Responses to Sucrose or Sucralose in Humans: A Pilot Study.

BACKGROUND: In light of obesity, replacing sugar with non-nutritive sweeteners is commonly used to reduce sugar content of food products. This study aimed to compare human energy expenditure (EE), carbohydrate oxidation and food intake after the ingestion of test foods sweetened with sucrose or a non-nutritive sweetener. METHODS: This was an acute crossover feeding study that entailed consumption of three test foods: jelly sweetened with 50 g sucrose (SUCROSE), with 120 mg of sucralose only (NNS), or 120 mg sucralose but matched in carbohydrate with 50 g maltodextrin (MALT). On test days, participants arrived at the research facility after an overnight fast. Resting energy expenditure (indirect calorimeter) was measured for 30 min followed by jelly consumption. Participants' EE and substrate oxidation were measured for 90 min subsequently. After EE assessment, participants completed a meal challenge before leaving the research facility, and recorded food intake for the remaining day. Subjective appetite ratings were assessed before and after test foods and meal challenge. RESULTS: Eleven participants completed the study. EE was higher in SUCROSE and MALT than NNS, but not statistically significant. Carbohydrate oxidation was SUCROSE > MALT > NNS (p < 0.001). Earlier and bigger rise in carbohydrate oxidation was observed in SUCROSE than MALT, although both were carbohydrate-matched. NNS did not promote energy expenditure, carbohydrate oxidation or stimulate appetite. CONCLUSIONS: Foods sweetened with sucrose or non-nutritive sweeteners but matched in carbohydrate content have different effects on human EE and carbohydrate oxidation. Sucralose alone did not affect EE, but lower energy in the test food from sugar replacement was eventually fully compensated. Findings from this pilot study should be verified with bigger clinical studies in the future to establish clinical relevance.

Effects of dipeptidyl peptidase IV inhibition on glycemic, gut hormone, triglyceride, energy expenditure, and energy intake responses to fat in healthy males.

Fat is the most potent stimulus for glucagon-like peptide-1 (GLP-1) secretion. The aims of this study were to determine whether dipeptidyl peptidase IV (DPP-IV) inhibition would enhance plasma active incretin [glucose-dependent insulinotropic polypeptide (GIP), GLP-1] concentrations and modulate the glycemic, gut hormone, triglyceride, energy expenditure, and energy intake responses to intraduodenal fat infusion. In a double-blind, randomized, placebo-controlled crossover design, 16 healthy lean males received 50 mg vildagliptin (V), or matched placebo (P), before intraduodenal fat infusion (2 kcal/min, 120 min). Blood glucose, plasma insulin, glucagon, active GLP-1, and GIP and peptide YY (PYY)-(3-36) concentrations; resting energy expenditure; and energy intake at a subsequent buffet meal (time = 120-150 min) were quantified. Data are presented as areas under the curve (0-120 min, means ± SE). Vildagliptin decreased glycemia (P: 598 ± 8 vs. V: 573 ± 9 mmol·l⁻¹·min⁻¹, P < 0.05) during intraduodenal lipid. This was associated with increased insulin (P: 15,964 ± 1,193 vs. V: 18,243 ± 1,257 pmol·l⁻¹·min⁻¹, P < 0.05), reduced glucagon (P: 1,008 ± 52 vs. V: 902 ± 46 pmol·l⁻¹·min⁻¹, P < 0.05), enhanced active GLP-1 (P: 294 ± 40 vs. V: 694 ± 78 pmol·l⁻¹·min⁻¹) and GIP (P: 2,748 ± 77 vs. V: 4,256 ± 157 pmol·l⁻¹·min⁻¹), and reduced PYY-(3-36) (P: 9,527 ± 754 vs. V: 4,469 ± 431 pM/min) concentrations compared with placebo (P < 0.05, for all). Vildagliptin increased resting energy expenditure (P: 1,821 ± 54 vs. V: 1,896 ± 65 kcal/day, P < 0.05) without effecting energy intake. Vildagliptin 1) modulates the effects of intraduodenal fat to enhance active GLP-1 and GIP, stimulate insulin, and suppress glucagon, thereby reducing glycemia and 2) increases energy expenditure. These observations suggest that the fat content of a meal, by enhancing GLP-1 and GIP secretion, may contribute to the response to DPP-IV inhibition.

The endocannabinoid arachidonylethanolamide attenuates aspects of lipopolysaccharide-induced changes in energy intake, energy expenditure and hypothalamic Fos expression.

Arachidonylethanolamide (AEA), an endocannabinoid, regulates both appetite and the immune system. The present study investigated in the rat the ability of AEA (1mg/kg, s.c.) to attenuate the lipopolysaccharide (LPS)-induced (100µg/kg, i.p.) changes in metabolic indices and Fos expression within hypothalamic and mesolimbic systems. AEA attenuated LPS-induced fever and hypophagia, abolished LPS-induced decreases in Fos expression within the arcuate and ventromedial nucleus of the hypothalamus, while both AEA and LPS independently increased Fos expression within the nucleus accumbens. These results highlight the importance of hypothalamic and mesolimbic systems in the regulation of appetite and energy partitioning.

[Role of the brain in the regulation of metabolism and energy expenditure: the central role of insulin, and insulin resistance of the brain]. / Az agy szerepe az anyagcsere és energiaforgalom szabályozásában: az inzulin központi idegrendszeri hatásai, az agy inzulinrezisztenciája.

Regulatory role of the brain in energy expenditure, appetite, glucose metabolism, and central effects of insulin has been prominently studied. Certain neurons in the hypothalamus increase or decrease appetite via orexigenes and anorexigenes, regulating energy balance and food intake. Hypothalamus is the site of afferent and efferent stimuli between special nuclei and beta- and alpha cells, and it regulates induction/inhibition of glucose output from the liver. Incretines, produced in intestine and in certain brain cells (brain-gut hormones), link to special receptors in the hypothalamus. Central role of insulin has been proved both in animals and in humans. Insulin gets across the blood-brain barrier, links to special hypothalamic receptors, regulating peripheral glucose metabolism. Central glucose sensing, via "glucose-excited" and "glucose-inhibited" cells have outstanding role. Former are active in hyperglycaemia, latter in hypoglycaemia, via influencing beta- and alpha cells, independently of traditional metabolic pathways. Evidence of brain insulin resistance needs centrally acting drugs, paradigm changes in therapy and prevention of metabolic syndrome, diabetes, cardiovascular and oncological diseases.

Presence or absence of carbohydrates and the proportion of fat in a high-protein diet affect appetite suppression but not energy expenditure in normal-weight human subjects fed in energy balance.

Two types of relatively high-protein diets, with a normal or low proportion of carbohydrates, have been shown effective for weight loss. The objective was to assess the significance of the presence or absence of carbohydrates and the proportion of fat in high-protein diets for affecting appetite suppression, energy expenditure, and fat oxidation in normal-weight subjects in energy balance. Subjects (aged 23 (sd 3) years and BMI 22·0 (sd 1·9) kg/m2) were stratified in two groups. Each was offered two diets in a randomised cross-over design: group 1 (n 22) - normal protein (NP; 10, 60 and 30 % energy (En%) from protein, carbohydrate and fat), high protein (HP; 30, 40 and 30 En%); group 2 (n 23) - normal protein (NP-g; 10, 60 and 30 En%), high protein, carbohydrate-free (HP-0C; 30, 0 and 70 En%) for 2 d; NP-g and HP-0C were preceded by glycogen-lowering exercise (day 1). Appetite was measured throughout day 2 using visual analogue scales (VAS). Energy expenditure (EE) and substrate oxidation (respiratory quotient; RQ) were measured in a respiration chamber (08.00 hours on day 2 until 07.30 hours on day 3). Fasting plasma ß-hydroxybutyrate (BHB) concentration was measured (day 3). NP-g and NP did not differ in hunger, EE, RQ and BHB. HP-0C and HP v. NP-g and NP, respectively, were lower in hunger (P < 0·05; P < 0·001) and RQ (P < 0·01; P < 0·001) and higher in EE (P < 0·05; P = 0·07) and BHB (P < 0·05; P < 0·001). Hunger and RQ were lower with HP-0C than HP (693 (sd 208) v. 905 (sd 209) mm VAS × 24 h, P < 0·01; 0·76 (sd 0·01) v. 0·81 (sd 0·02), P < 0·01); BHB was higher (1349 (sd 653) v. 332 (sd 102) µmol/l; P < 0·001). ΔHunger, ΔRQ, and ΔBHB were larger between HP-0C-NP-g than between HP-NP ( - 346 (sd 84) v. - 107 (sd 52) mm VAS ×  24 h, P < 0·01; - 0·09 (sd 0·00) v. - 0·05 (sd 0·00), P < 0·001; 1115 (sd 627) v. 104 (sd 42) µmol/l, P < 0·001). In conclusion, appetite suppression and fat oxidation were higher on a high-protein diet without than with carbohydrates exchanged for fat. Energy expenditure was not affected by the carbohydrate content of a high-protein diet.

C-type natriuretic peptide as a new regulator of food intake and energy expenditure.

The physiological implication of C-type natriuretic peptide (CNP) including energy metabolism has not been elucidated, because of markedly short stature in CNP-null mice. In the present study we analyzed food intake and energy expenditure of CNP-null mice with chondrocyte-targeted CNP expression (CNP-Tg/Nppc(-/-) mice), in which marked skeletal dysplasia was rescued, to investigate the significance of CNP under minimal influences of skeletal phenotypes. In CNP-Tg/Nppc(-/-) mice, body weight and body fat ratio were reduced by 24% and 32%, respectively, at 20 wk of age, and decreases of blood glucose levels during insulin tolerance tests were 2-fold exaggerated at 17 wk of age, as compared with CNP-Tg/Nppc(+/+) mice. Urinary noradrenalin excretion of CNP-Tg/Nppc(-/-) mice was greater than that of CNP-Tg/Nppc(+/+) mice by 28%. In CNP-Tg/Nppc(-/-) mice, rectal temperature at 1600 h was higher by 1.1 C, and uncoupling protein-1 mRNA expression in the brown adipose tissue was 2-fold increased, which was canceled by propranolol administration, as compared with CNP-Tg/Nppc(+/+) mice. Oxygen consumption was significantly increased in CNP-Tg/Nppc(-/-) mice compared with that in CNP-Tg/Nppc(+/+) mice. Food intake of CNP-Tg/Nppc(-/-) mice upon ad libitum feeding and refeeding after 48 h starvation were reduced by 21% and 61%, respectively, as compared with CNP-Tg/Nppc(+/+) mice. This study unveiled a new aspect of CNP as a molecule regulating food intake and energy expenditure. Further analyses on precise mechanisms of CNP actions would lead to the better understanding of the significance of the CNP/guanylyl cyclase-B system in food intake and energy expenditure.

Anorexia: aetiology, epidemiology and management in older people.

The loss of appetite is termed 'anorexia'. Dramatic and poorly understood alterations occur in the physiological regulation of appetite in older adults, who frequently exhibit less hunger and earlier satiety. Appetite regulation (and, therefore, food intake) is affected by a number of social, cultural and psychological factors, as well as by acute and chronic disease states, drugs, dementia or mood disorders. Self-reported anorexia has been reported by approximately one-third of older men and women. Recent development of validated measures of appetite aid in the approach to the problem. The differential diagnostic approach for appetite disturbances should follow from an understanding of the physiological, social, psychological and pathophysiological causes of anorexia. Emerging understanding of the association between proinflammatory cytokines and the anorexia/cachexia syndrome indicates that this process is the most commonly encountered underlying reason for anorexia in acute and chronically ill older persons. Despite the changes in appetite regulation in older persons, the response to social and psychological stimulants in this age group is similar to that in younger adults. Pharmacological stimulants of appetite appear to be a promising intervention for anorexia.

The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake.

For humans and animal models alike there is general agreement that the central nervous system processing of gastrointestinal (GI) signals arising from ingested food provides the principal determinant of the size of meals and their frequency. Despite this, relatively few studies are aimed at delineating the brain circuits, neurochemical pathways and intracellular signals that mediate GI-stimulation-induced intake inhibition. Two additional motivations to pursue these circuits and signals have recently arisen. First, the success of gastric-bypass surgery in obesity treatment is highlighting roles for GI signals such as glucagon-like peptide-1 (GLP-1) in intake and energy balance control. Second, accumulating data suggest that the intake-reducing effects of leptin may be mediated through an amplification of the intake-inhibitory effects of GI signals. Experiments reviewed show that: (1) the intake-suppressive effects of a peripherally administered GLP-1 receptor agonist is mediated by caudal brainstem neurons and that forebrain-hypothalamic neural processing is not necessary for this effect; (2) a population of medial nucleus tractus solitarius (NTS) neurons that are responsive to gastric distention is also driven by leptin; (3) caudal brainstem-targeted leptin amplifies the food-intake-inhibitory effects of gastric distention and intestinal nutrient stimulation; (4) adenosine monophosphate-activated protein kinase (AMPK) activity in NTS-enriched brain lysates is elevated by food deprivation and reduced by refeeding and (5) the intake-suppressive effect of hindbrain-directed leptin is reversed by elevating hindbrain AMPK activity. Overall, data support the view that the NTS and circuits within the hindbrain mediate the intake inhibition of GI signals, and that the effects of leptin on food intake result from the amplification of GI signal processing.

Control of food intake and energy expenditure by amylin-therapeutic implications.

Amylin is a pancreatic B-cell hormone that plays an important role in the control of nutrient fluxes because it reduces food intake, slows gastric emptying, and reduces postprandial glucagon secretion. These actions seem to depend on a direct effect on the area postrema (AP). Subsequent to area AP activation, the amylin signal is conveyed to the forebrain via distinct relay stations. Within the lateral hypothalamic area, amylin diminishes the expression of orexigenic neuropeptides. Recent studies suggest that amylin may also play a role as a long term, adiposity signal. Similar to leptin or insulin, an infusion of amylin into the brain resulted in lower body weight gain than in controls, irrespective of the starting body weight. Interestingly, preliminary data also suggest that rats fed an energy-dense diet develop resistance to central amylin. In addition to amylin's action to control meal termination and to act as a potential adiposity signal, amylin and its agonist salmon calcitonin have recently been shown to increase energy expenditure under certain conditions. In summary, amylin may be an interesting target as a body weight lowering drug. In fact, recent studies provide evidence that amylin, especially when combined with other anorectic hormones (for example, peptide YY and leptin) has beneficial long-term effects on body weight.

Hypothalamic neuronal histamine mediates the thyrotropin-releasing hormone-induced suppression of food intake.

We examined the involvement of thyrotropin-releasing hormone (TRH) and TRH type 1 and 2 receptors (TRH-R1 and TRH-R2, respectively) in the regulation of hypothalamic neuronal histamine. Infusion of 100 nmol TRH into the rat third cerebroventricle (3vt) significantly decreased food intake (p < 0.05) compared to controls infused with phosphate- buffered saline. This TRH-induced suppression of food intake was attenuated partially in histamine-depleted rats pre-treated with alpha-fluoromethylhistidine (a specific suicide inhibitor of histidine decarboxylase) and in mice with targeted disruption of histamine H1 receptors. Infusion of TRH into the 3vt increased histamine turnover as assessed by pargyline-induced accumulation of tele-methylhistamine (t-MH, a major metabolite of neuronal histamine in the brain) in the tuberomammillary nucleus (TMN), the paraventricular nucleus, and the ventromedial hypothalamic nucleus in rats. In addition, TRH-induced decrease of food intake and increase of histamine turnover were in a dose-dependent manner. Microinfusion of TRH into the TMN increased t-MH content, histidine decarboxylase (HDC) activity and expression of HDC mRNA in the TMN. Immunohistochemical analysis revealed that TRH-R2, but not TRH-R1, was expressed within the cell bodies of histaminergic neurons in the TMN of rats. These results indicate that hypothalamic neuronal histamine mediates the TRH-induced suppression of feeding behavior.

Sugar-sweetened and artificially sweetened soft drinks in association to restrained, external and emotional eating.

We studied sugar-sweetened soft drinks and light soft drinks in their associations to psychological constructs of eating behavior and demographic data for adults and children. Soft drink intakes were assessed by consumption of soft drinks in number of days the last week, and eating behavior was measured by the Dutch Eating Behaviour Questionnaire (DEBQ). The sample included 3265 men and women, and their 12-year old children, originating from Swedish national databases. Associations to younger age and lower education in adults were in particular apparent for sugar-sweetened soft drinks. Consumption of sugar-sweetened soft drinks was further associated to less restrained and more external eating in adults. In contrast, light soft drinks were associated with higher BMI, more restrained eating and also more emotional eating in adults. For the children these associations were generally weaker. Sugar-sweetened soft drinks are consumed by persons with a lower education, who furthermore are less prone to attempt to restrict their calorie intake, and by some of those who are sensitive to external stimuli of foods. Light soft drinks are rather chosen by the more heavy persons who try to restrict their energy intake perhaps in order to control the body weight, and more unexpectedly, by adults who eat for comfort. Being more sensitive to an external stimulus of food such as taste seems to imply proneness to consume sugar-sweetened soft drinks instead of the light versions. Light soft drinks may be perceived as an adequate substitute in the use of foods for comfort, meaning the sweet taste may be sufficient for this purpose.

Consumption of dietary supplements containing Citrus aurantium (bitter orange)--2004 California Behavioral Risk Factor Surveillance Survey (BRFSS).

BACKGROUND: Following the marketing ban of ephedra-containing supplements in April 2004, many manufacturers substituted the herb Citrus aurantium for ephedra and marketed the products as "ephedra-free" supplements. Extracts of C. aurantium contain synephrine, a sympathomimetic alkaloid. OBJECTIVE: To determine the prevalence of consumption of dietary supplements containing C. aurantium in California during 2004. METHODS: We used the 2004 California Behavioral Risk Factor Surveillance Survey to determine the prevalence of consumption of dietary supplements containing C. aurantium in California during 2004. RESULTS: Two percent (n = 70) of the 4140 survey respondents reported taking a dietary supplement containing C. aurantium in the previous year. Reasons stated included energy enhancement, weight loss, and appetite suppression. Compared with nonusers, users were more likely to report being single, aged 18-34 years, and Hispanic; consuming 3 or more alcoholic drinks on days that they imbibed; and having a heavier body mass index. Among the 5 users who reported experiencing an adverse event that they attributed to the supplement, 3 indicated that the severity was mild. CONCLUSIONS: Given that supplements containing ephedra were banned in April 2004, the results from this study may serve as a baseline estimate against which future studies of the use of C. aurantium products may be compared.

Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents.

The conditioned taste aversion (CTA) is routinely used to assess the aversive consequences of anorexic agents, including potential pharmacological therapies for obesity. In a typical CTA paradigm, rats briefly sampling a novel tastant (e.g., saccharin) are acutely administered with toxin (e.g., lithium chloride, LiCl). After as few as one taste-toxin pairing, rats will reliably avoid the novel tastant. This paradigm is frequently used for the assessment of possible aversive consequences of drugs that are candidates for pharmacological therapies. The degree to which the drug supports development of a CTA is interpreted as an index of its aversive properties. Difficulties with previous work include the inability to assess affects on food intake and CTA simultaneously, particularly during chronic drug administration. We report here two novel CTA paradigms for the assessment of appetitive and aversive consequences of anorexic agents, simultaneously. In the first experiment, animals receive an intraoral infusion of a novel and highly palatable tastant immediately prior to administration of increasing doses of LiCl. In the second experiment, rats were implanted intraperitoneally with osmotic minipumps that chronically delivered a low dose of LiCl for 7 days. LiCl did not affect short or long term food intake in either experiment. However, LiCl did support the development of a CTA in both paradigms. These results suggest that both the appetitive and aversive consequences of anorexic agents can be assessed simultaneously during either acute or chronic drug administration.

Sucrose intake as a function of its cost and the cost of chow.

The avid consumption of pure carbohydrate solutions, which often results in a distortion of nutrient balance, is generally presumed to be driven by their taste. In the first of two experiments, we examined the effect of consumption cost on rats' intake of three concentrations of sucrose solution (8%, 16%, and 32%) when a nutritionally complete chow was concurrently freely available. In the second experiment, we examined the intake of 24% sucrose solution and chow as the consumption costs of both were varied. Increasing the cost of sucrose resulted in a reduction in the percent calories taken from sucrose; the steepness of the decline in intake with price was inversely related to the sucrose concentration and to the cost of chow. Chow calories were substituted for relatively expensive sucrose calories. An increase in the cost of chow resulted in a reduction in the percent of calories taken from chow and a protein-poor diet. The cost of sucrose did not affect the slope of the chow intake curve, presumably because, despite its sweet taste, sucrose was not a substitute for the protein, fat, and micronutrients in chow. Total caloric intake was conserved in all cases.Thus, the avid consumption of sucrose solution is curtailed when it is costly; but the degree of change in intake with cost depends on the cost of an alternative food. These results suggest that diet selection involves a comparison not only of the taste and post-ingestive consequences of available foods, but also of the cost of calories and nutrients in the foods. Selection appears to be guided first by caloric requirements and the relative cost of calories, then by nutrient requirements and the relative cost of nutrients, and finally by taste.