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News in gut-brain communication: a role of peptide YY (PYY) in human obesity and following bariatric surgery?

Recent advances in obesity research focused on neuroendocrine control of food intake, appetite and body weight balance. Gut hormones, which are sequentially released from different regions of the gut, send signals to the areas of appetite control in the central nervous system causing a release of counter-regulatory hormones also originating from the gastrointestinal system. Ghrelin, a peptide secreted from the gastric fundus is released just before meal intake and stimulates hunger and food intake. Recently, peptide YY has been suggested to counteract ghrelin by inducing satiety and reducing appetite and caloric intake. While the effects of PYY on various gastrointestinal functions are well described, its action on weight loss is less known. Controversial results on the effect of exogenous administration of PYY(3-36) opened the discussion on the respective roles of PYY and/or PYY(3-36) in body weight homeostasis in man.

Appetite Regulation↗

Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes.

BACKGROUND: It is not known how a low-carbohydrate, high-protein, high-fat diet causes weight loss or how it affects blood glucose levels in patients with type 2 diabetes. OBJECTIVE: To determine effects of a strict low-carbohydrate diet on body weight, body water, energy intake and expenditure, glycemic control, insulin sensitivity, and lipid levels in obese patients with type 2 diabetes. DESIGN: Inpatient comparison of 2 diets. SETTING: General clinical research center of a university hospital. PATIENTS: 10 obese patients with type 2 diabetes. INTERVENTION: Usual diets for 7 days followed by a low-carbohydrate diet for 14 days. MEASUREMENTS: Body weight, water, and composition; energy intake and expenditure; diet satisfaction; hemoglobin A1c; insulin sensitivity; 24-hour urinary ketone excretion; and plasma profiles of glucose, insulin, leptin, and ghrelin. RESULTS: On the low-carbohydrate diet, mean energy intake decreased from 3111 kcal/d to 2164 kcal/d. The mean energy deficit of 1027 kcal/d (median, 737 kcal/d) completely accounted for the weight loss of 1.65 kg in 14 days (median, 1.34 kg in 14 days). Mean 24-hour plasma profiles of glucose levels normalized, mean hemoglobin A1c decreased from 7.3% to 6.8%, and insulin sensitivity improved by approximately 75%. Mean plasma triglyceride and cholesterol levels decreased (change, -35% and -10%, respectively). LIMITATIONS: The study was limited by the short duration, small number of participants, and lack of a strict control group. CONCLUSION: In a small group of obese patients with type 2 diabetes, a low-carbohydrate diet followed for 2 weeks resulted in spontaneous reduction in energy intake to a level appropriate to their height; weight loss that was completely accounted for by reduced caloric intake; much improved 24-hour blood glucose profiles, insulin sensitivity, and hemoglobin A1c; and decreased plasma triglyceride and cholesterol levels. The long-term effects of this diet, however, remain uncertain.

Appetite↗

Energy intake: its relationship to colon cancer risk.

A case-control study was conducted to assess the role of diet in the etiology of colon cancer. Diet was measured by means of a comprehensive quantifiable food frequency history instrument in 246 cases and 484 controls drawn from the general population of Utah. Each subject's diet was described by major nutrient groups and total energy based on the nutritional content of foods reported. Cases reported higher daily food intake 5 years preceding diagnosis than controls [men, rate ratio (RR) = 2.5; women, RR = 3.6], as measured by total energy content of the diet. Higher risk of colon cancer with increasing energy intake was independent of stage of disease at diagnosis and obesity, as measured by body mass. Fat, protein, and carbohydrate intake all had elevated RRs but could not be assessed as risk factors independent of energy intake because of their strong correlations with total calories. Due to the higher energy intake of the cases, odds ratios for the daily intake of dietary fiber and vitamins A and C were also greater than 1. However, adjusting for caloric intake removed this effect, and dietary fiber showed a weak protective effect. Total energy intake must be evaluated before attempting to assign a causal role to any food or nutrient that may be postulated to play a role in colon cancer.

Adult↗

Dietary compliance for pediatric burned patients.

Physician diet orders written for pediatric burned patients frequently differ from the diets patients actually receive. At Shriners Burns Institute in Boston, such deviations from the diet order were generally not recognized for at least two days. In order to increase compliance with physician diet orders, changes in the nutritional support program were implemented which included physician diet orders containing specific macronutrient requirements in addition to the caloric goal, which was changed in response to recent research demonstrating that the previously used formula provided excessive calories; introduction of modular diets for parenteral and enteral feedings; institution of daily nutrition flow sheets; and a change of the time at which daily caloric intake records were calculated. In order to assess the benefits of the new measures, the average deviation from the caloric goal was calculated for patients who did not receive the new assessment tools (control group, N = 51), compared with those who did (study group, N = 50). Least squares regression analysis indicated a trend toward improved compliance and less deviation from the calculated caloric goal following implementation of the four measures.

Adolescent↗

Morinda revisited: changes in nutritional well-being and gender differences after 30 years of rapid economic growth in rural Punjab, India.

A follow-up study of malnutrition and its determinants among children 6 to 24 months of age was carried out in rural areas of Punjab State in India 30 years after the original study, and following a period of rapid economic growth. The original 1971 study had found a high prevalence of mortality and malnutrition and the worst gender difference in nutritional status ever recorded in an Indian study. The 2001 follow-up study found dramatic reductions in child mortality, child malnutrition, gender-based imbalances in child well-being and care, and family size, the result of participatory economic growth coupled with broad-based educational, health, and family-planning services. Despite overall improvements in caloric intake, however, 40% of lower-class children in 2001 were still consuming less than 50% of their caloric allowance. With minimal gender-based abortion and significantly reduced neglect and mortality offemale children, gender balance among children in this area of rural Punjab improved markedly over the 30-year period.

Child Nutrition Disorders↗

Effect of glucagon in macronutrient self-selection: glucagon-enhanced protein intake.

The effect of glucagon on macronutrient selection was studied using rats. Continuous infusion of glucagon (5 ng/microliters/h) into the lateral cerebral ventricle increased total caloric intake and protein selection, and decreased carbohydrate selection. Continuous infusion of glucagon subcutaneously induced similar changes. Since a hyperglycemic response to the intracranial injection of 2-deoxy-D-glucose (2DG) disappeared in rats either with bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) (17) or with acquired (21) and congenital (10) blindness, and bilateral lesions of the SCN eliminated the hyperglucagonemic response to the 2DG-injection (19), changes in the plasma glucagon concentration after 2DG injection were examined in acquired and congenital blind rats. Consequently, it was found that the hyperglucagonemic response to 2DG was not observed in those blind rats which lacked the hyperglycemic response. In those SCN-lesioned and blind rats lacking the hyperglucagonemic response to 2DG, the protein selection was lower, and carbohydrate selection tended to be higher, than those selections found in the control rats. Considering the neural connection between the retina and the SCN, these findings suggest that glucagon may have a stimulatory effect on protein intake and a suppressive one for carbohydrate intake; and that the SCN may be involved in such a regulatory mechanism of feeding behavior through controlling the blood glucagon level.

Animal Nutritional Physiological Phenomena↗

The effect of dietary cholesterol, energy intake, and oxygen consumption on cholesterol metabolism in the chick.

This experiment, involving 320 chicks, was conducted to determine the effects of dietary cholesterol, restricted caloric intake, and genetic lines on cholesterol metabolism in the bird. The two lines of chicks studied had been divergently selected for oxygen consumption and had been shown to differ significantly (P less than .01) in weight gain and carcass lipid deposition. The dietary treatments, administered for a 2-week period, consisted of two levels of dietary cholesterol (none and supplemented) for each of two levels of energy (ad libitum and restricted). At the end of this 2-week period, the birds were injected intravenously with 1-14C-acetate and their livers removed 4 hr later. Hepatic cholesterol and lipid synthesis were measured by the uptake of acetate. Added dietary cholesterol significantly (P less than .01) decreased hepatic cholesterol synthesis, lipid synthesis, and specific activity of hepatic cholesterol but increased plasma and liver cholesterol. However, the elevation in plasma and liver cholesterol represented only .9 and 1.8% respectively, of the increase in total intake of dietary cholesterol. Metabolizable energy of diets fed ad libitum was also significantly (P less than .01) reduced with supplemented dietary cholesterol. A significant (P less than .01) difference in body weight was present between the two lines, with low oxygen consuming (LOC) birds exhibiting heavier body weights than high oxygen consuming (HOC) birds. A significant interaction between line and energy intake (P less than .05) was present for hepatic cholesterol levels; LOC birds exhibited higher levels of hepatic cholesterol than HOC birds when both groups were fed at restricted levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Short-term control of feeding: limitation of the glucostatic theory.

In the rat, the short-term effect on spontaneous feeding of intravenous administration of either glucose or glucose plus insulin was investigated. The infusions lasted 4 hours and covered 170% of rats's previously measured spontaneous caloric intake, while control infusions of saline and saline plus insulin were also made. Feeding patterns in subjects' home cages were recorded. Glycaemia and glycosuria were measured in order to asses glucose utilization. When it was infused alone, glucose was utilized at 95% and so covered 160% of oral caloric requirements, while the reduction of oral intake was only 40%. When insulin was co-infused with glucose, utilization reached 100% and oral feeding was reduced by 70%. Saline infusions did not affect oral feeding, and insulin brought about the expected increase in feeding. It is proposed that the mechanism which sustains feeding should depend on multiple macronutrients utilization rather than on one specific chemical family. Furthermore, the fact that insulin has a clear-cut effect, despite its lipogenetic, i.e., metabolite-sequestering properties, favors the ischymetric hypothesis (based on cellular power-production), rather than the energostatic one (based on yields of nutrients).

Animals↗

Aspects of the control of feeding: application of quantitation in psychobiology.

In rhesus monkeys equipped with indwelling gastric cannulae and studied in the unanesthetized state, it is possible to demonstrate that their feeding is a precisely regulated behavior functioning to maintain caloric intake quite constant. The infusion of nutrients into the stomach through the cannula results in a reduction in their feeding by an amount that is equivalent to the caloric value of the infusion. A similar precise recovery from caloric deficits by overeating can also be demonstrated. One means of controlling intake of food may derive from a remarkable change in gastric function that occurs with feeding. If the stomach is filled with non-nutrient saline it functions like a physiological "pump" expelling its contents into the small bowel in an exponential fashion--more rapidly with increasing volume. If the stomach is filled with nutrients then it functions like a precise "valve," delivering its contents at a constant and linear rate of 0.4 kcal/min to the duodenum regardless (within limits) of the volume, concentration or character (carbohydrate, fat, protein) of the nutrient meal. This change in gastric activity is provoked by the calories that are passed into the duodenum and sustained for a period depending on the amount of calories in the duodenum. The relation of these physiological events to the control of feeding is discussed.

Animals↗

Caloric restriction prevents age-related decline in skeletal muscle dihydropyridine receptor and ryanodine receptor expression.

The dihydropyridine receptor (DHPR), a voltage-gated L-type Ca2+ channel, and the Ca2+ release channel/ryanodine receptor isoform-1 (RyR1) are key molecules involved in skeletal muscle excitation-contraction coupling. We have reported age-related decreases in the level of DHPR expression in fast- and slow-twitch muscles from Fisher 344 cross Brown Norway (F344BNX) rats (Renganathan, Messi and Delbono, J. Membr. Biol. 157 (1997) 247-253). Based on these studies we postulate that excitation-contraction uncoupling is a basic mechanism for the decline in muscle force with aging (Delbono, Renganathan and Messi, Muscle Nerve Suppl. 5 (1997) S88-92). In the present study, we extended our studies to older ages and we intended to prevent or retard excitation-contraction uncoupling by restricting the caloric intake of the F344BNX rats from 16 weeks of age. Three age groups, 8-, 18-, and 33-month old caloric restricted rats, were compared with ad libitum fed animals. The number of DHPR and RyR1 and DHPR/RyR1 ratio (an index of the level of receptors uncoupling) in skeletal muscles of 8-month and 18-month rats was not significantly different in either ad libitum fed or caloric restricted rats. However, the age-related decrease in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in 33-month old ad libitum fed rats was absent in 33-month old caloric restricted rats. These results suggest that caloric restriction prevents age-related decreases in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in fast- and slow-twitch rat skeletal muscles.

Aging↗

The effect on health of alternate day calorie restriction: eating less and more than needed on alternate days prolongs life.

Restricting caloric intake to 60-70% of normal adult weight maintenance requirement prolongs lifespan 30-50% and confers near perfect health across a broad range of species. Every other day feeding produces similar effects in rodents, and profound beneficial physiologic changes have been demonstrated in the absence of weight loss in ob/ob mice. Since May 2003 we have experimented with alternate day calorie restriction, one day consuming 20-50% of estimated daily caloric requirement and the next day ad lib eating, and have observed health benefits starting in as little as two weeks, in insulin resistance, asthma, seasonal allergies, infectious diseases of viral, bacterial and fungal origin (viral URI, recurrent bacterial tonsillitis, chronic sinusitis, periodontal disease), autoimmune disorder (rheumatoid arthritis), osteoarthritis, symptoms due to CNS inflammatory lesions (Tourette's, Meniere's) cardiac arrhythmias (PVCs, atrial fibrillation), menopause related hot flashes. We hypothesize that other many conditions would be delayed, prevented or improved, including Alzheimer's, Parkinson's, multiple sclerosis, brain injury due to thrombotic stroke atherosclerosis, NIDDM, congestive heart failure. Our hypothesis is supported by an article from 1957 in the Spanish medical literature which due to a translation error has been construed by several authors to be the only existing example of calorie restriction with good nutrition. We contend for reasons cited that there was no reduction in calories overall, but that the subjects were eating, on alternate days, either 900 calories or 2300 calories, averaging 1600, and that body weight was maintained. Thus they consumed either 56% or 144% of daily caloric requirement. The subjects were in a residence for old people, and all were in perfect health and over 65. Over three years, there were 6 deaths among 60 study subjects and 13 deaths among 60 ad lib-fed controls, non-significant difference. Study subjects were in hospital 123 days, controls 219, highly significant difference. We believe widespread use of this pattern of eating could impact influenza epidemics and other communicable diseases by improving resistance to infection. In addition to the health effects, this pattern of eating has proven to be a good method of weight control, and we are continuing to study the process in conjunction with the NIH.

Caloric Restriction↗

Energy, nutrient intake and prostate cancer risk: a population-based case-control study in Sweden.

The role of diet in the etiology of prostate cancer remains unclear, because results from several case-control and cohort studies on fat intake and risk of prostate cancer have been inconsistent; few of the studies have adjusted the results for caloric intake. To examine the relationship between energy, intake of several nutrients and risk of prostate cancer (all stages combined and advanced stages separately), we conducted a population-based case-control study in Orebro County, Sweden, from 1989 through 1994. A total of 526 patients with newly diagnosed prostate cancer and 536 controls, randomly selected from the population register and frequency-matched by age, were included in the analyses. Information about dietary intake was obtained from a self-administered semi-quantitative food frequency questionnaire. Odds ratios with 95% confidence intervals were estimated by unconditional logistic regression. In age-adjusted analyses, there were positive associations of prostate cancer (all stages combined) risk with total energy intake as well as intake of total fat (saturated and monounsaturated), protein, retinol and zinc. The positive association with energy intake was stronger for advanced cancer, with an excess risk of 70% for the highest quartile vs. the lowest. After adjustment for energy intake, there was no apparent association of prostate cancers (all stages combined) with any of the investigated nutrients. However, a weak positive association between intake of retinol and advanced cancer was observed. We conclude that our results provide some evidence that total energy intake is a risk factor for prostate cancer.

Adult↗

Behavioral analysis of marijuana effects on food intake in humans.

Nine male research volunteers, in three groups of three subjects each, resided in a residential laboratory for up to 25 days. All contact with the experimenter was through a networked computer system and subjects' behaviors including food intake were continuously recorded. Subjects brought their own activities such as model-making, and these in combination with those provided by the laboratory resulted in rich behavior repertoires. During the first part of the day, subjects remained in their private rooms doing planned work activities, and during the remainder of the day, they were allowed to socialize. Cigarettes containing active marijuana (1.84% THC) or placebo were smoked prior to the private work period and during the social access period. A single active marijuana cigarette prior to the private work period had no effect on food intake. The administration of two or three active marijuana cigarettes during the social access period increased average daily caloric intake. The increased intake was due to an augmentation of calories consumed as between-meal snack items rather than an increase in meal size per se.

Adult↗

Trends in mortality, body weights and tumor incidences of Wistar rats over 20 years.

Historical data of more than 8,000 Wistar rats (designation: WISW SPF Cpb) used as controls in seventy 2-year studies terminated between 1975 and 1994 were analyzed for time trends in food consumption, terminal body weight, mortality, and tumor incidences. In males there was a significant (p < 0.01) time trend towards higher terminal body weight and a tendency (p > 0.05) to lower incidences of pituitary tumors and adrenal pheochromocytomas, while mortality remained stable. Leydig cell tumors showed a significant (p = 0.0005) positive trend. In females, terminal body weight did not increase over time but pituitary and mammary tumors showed a marked and highly significant (p = 0.0001) increase, which explains a significant (p = 0.0045) positive trend in mortality. There was a significant (p = 0.0001) negative time trend for uterine adenomas/carcinomas and a slight tendency (p = 0.4135) towards a decreased incidence of endo-metrial stromal polyps. Since the average food intake data do not indicate a time trend the changes observed might probably not be related to higher caloric intake. In contrast to other authors we could not find a positive correlation between either body weight and incidences of pituitary tumors or body weight and mortality. Certain selection measures at breeding and/or a genetic drift over time might explain the time trends observed. This data does not yet indicate a need for a change in ad-libitum feeding of these animals.

Animals↗

[Pregnancy and nutrition].

Based on the active role of the placenta fetal nutrient supply is to a large degree independent on the nutrition of the mother. The fetus must be considered as a parasite within the maternal organism and only with extreme reduction in nutritional intake by the mother will an effect on fetal growth become apparent. Mild chronic forms of inadequate food intake may lead to depletion of maternal reserves, in particular of minerals and vitamins, and as a consequence of the extra demands during pregnancy supply of maternal tissues may be short. Special high risk groups for inadequate nutrition during pregnancy are defined and intense counseling of these mothers must be part of prenatal care. An increased intake of food with high nutritional value, i.e. a high content in minerals and vitamins relative to the caloric content, should be the basis of good nutrition in pregnancy. This will satisfy extra demands of these substances without increasing caloric intake.

Adolescent↗

Nutrient intake and blood pressure: families of adult identical twins.

To investigate the relationship of dietary intake to blood pressure, 198 adults and 53 children who were members of 92 nuclear families completed a 3-day diet diary prior to an outpatient clinic examination for cardiovascular disease risk factors. Nutrient intake was significantly related to age and anthropometric variables in adults. Sodium and potassium intake were related to blood pressure in adults, but this relationship was no longer significant after adjustment for caloric intake. The diet and blood pressure relationships in children were less clear. Multiple linear regression techniques using age, anthropometric variables, and nutrient intake demonstrated that in adults age and skinfold were the principal determinants of blood pressure, but in children age and saturated fat intake were most likely to enter the equations. In comparisons of normotensive and hypertensive adults, there were no differences in the dietary intakes of these electrolytes. The results of this investigation underscore the complex interaction of nutrient intake with body size and age. Investigators who focus only on a few nutrients and fail to account for other sources of variation can be misled.

Adult↗

Monitoring energy balance: metabolites of fatty acid synthesis as hypothalamic sensors.

Because energy balance is important for survival, a system is required to monitor energy status and to make appropriate adjustments in energy intake and energy expenditure. In higher animals, a centrally located system has evolved to accomplish this task. When caloric intake exceeds expenditure, the surplus is channeled into energy storage pathways, primarily the synthesis of fatty acids, which are converted into fat and stored in adipose tissue. Thus, metabolic flux through the pathway of fatty acid synthesis, located in the lipogenic tissues, reflects the "energy status" of the animal. The enzymatic machinery of this pathway is also expressed in the brain, notably the hypothalamus. In the hypothalamus, intermediates in this pathway appear to serve as energy sensors that signal higher brain centers to produce appropriate responses, e.g., altered food intake and energy expenditure.

Acyl Coenzyme A↗

Food intake by brain-injured humans who are in the chronic phase of recovery.

This study examined whether survivors of traumatic brain injury differ from normal, non-injured controls in the regulation of food intake in their natural environment. Caregivers of 20 brain-injured subjects and 20 controls recorded in diaries: caloric intake, time of meals, subjective hunger ratings, and the number of persons present during meals for 7 consecutive days. Brain-injured subjects ate larger meals and more total (overall) calories per day compared with controls. In addition, the presence of other people during a meal, or social factor, was a significant predictor of meal size for the control subjects, but not for the brain-injured subjects. Brain-injured subjects also differed from control subjects in their response to pre-meal stomach content.

Activities of Daily Living↗