Decrease In Meal Frequency Research Articles

The Dietary Pattern and Hemoglobin Status of School-Age Children in Odeda Local Government Area of Ogun State in Nigeria

Iron deficiency is the most common case of micronutrient deficiency in the world and widely known to cause anemia. School-age children are at high risk of micronutrient deficiency due to increased energy expenditure, combined with decreased meal frequency and insufficient maternal attention as well as parasitic infections. This study assessed the dietary pattern and hemoglobin status of school-age children in Odeda Local Government area of Ogun State in Nigeria. Two-hundred-and-twenty-seven (227) children from two schools were recruited for the study. Data on the socio-demographic characteristics of the respondents and consumption pattern were obtained through a semi-structured questionnaire. Anthropometric measurements (height and weight) of the children were determined using standard anthropometric procedures, while anthropometric indices were measured against WHO growth standard. Blood samples of the subjects were collected and analysed for haematological variables (haemoglobin, serum transferrin, and serum ferritin). Data were analyzed using frequency count, percentage, and mean. Research results have revealed that regular consumption of fruits is generally low (6.8%) among respondents. Most of the respondents (61.0%) consume green leafy vegetables on a regular basis, while 54.3% and 46.3% consume meat and fish more than 4 times per week, respectively. The anthropometric measurement of the subjects at baseline shows that 17.2% are severely stunted (HAZ-3SD), 19.5% are moderately stunted (-3SD<HAZ<-1SD), and 39.4% are mildly stunted (‐2 SD < HAZ <‐1 SD). The BAZ status record that 14.1% are underweight (BAZ<-2SD), 1.4% are overweight (2 SD > BAZ >1 SD), and 0.8% are identified with obesity (BAZ >2 SD). Biochemical status shows that 54.9% are anemic, while all (100.0%) of the children have adequate ferritin and transferrin status. This study has acknowledged that school-age children in Odeda local government face serious prevalence of anemia associated with causes beyond the lack of iron-rich food sources.

Food intake, and anthropometrical and biological parameters in adult Tunisians during Ramadan

We evaluated the effects of fasting during Ramadan on nutritional intake and plasma lipoproteins in 20 healthy adults of normal weight. A 5-day food questionnaire was completed for every participant. Clinical investigations, anthropometrical measurements and laboratory analysis were also undertaken. Body weight, blood pressure and blood glucose were not influenced by fasting but there were non-significant modifications in the plasma lipid fractions. The total cholesterol remained unchanged. Total daily energy intake was comparable before, during and after Ramadan despite the decrease in meal frequency during fasting. Thus fasting in Ramadan did not affect dietary intake, clinical, anthropometrical and most biological parameters

Beneficial effects of a decreased meal frequency on nutrient utilization, secretion of luteinizing hormones and ovarian follicular development in gilts

BackgroundReplacement gilts are typically fed ad libitum, whereas emerging evidence from human and rodent studies has revealed that time-restricted access to food has health benefits. The objective of this study was to investigate the effect of meal frequency on the metabolic status and ovarian follicular development in gilts.MethodsA total of 36 gilts (Landrace × Yorkshire) with an age of 150±3 d and a body weight of 77.6±3.8 kg were randomly allocated into one of three groups (n = 12 in each group), and based on the group allocation, the gilts were fed at a frequency of one meal (T1), two meals (T2), or six meals per day (T6) for 14 consecutive weeks. The effects of the meal frequency on growth preference, nutrient utilization, short-chain fatty acid production by gut microbial, the post-meal dynamics in the metabolic status, reproductive hormone secretions, and ovarian follicular development in the gilts were measured.ResultsThe gilts in the T1 group presented a higher average daily gain (+ 48 g/d, P < 0.05) and a higher body weight (+ 4.9 kg, P < 0.05) than those in the T6 group. The meal frequency had no effect on the apparent digestibility of dry matter, crude protein, ether extract, ash, and gross energy, with the exception that the T1 gilts exhibited a greater NDF digestibility than the T6 gilts (P < 0.05). The nitrogen balance analysis revealed that the T1 gilts presented decreased urine excretion of nitrogen (− 8.17 g/d, P < 0.05) and higher nitrogen retention (+ 9.81 g/d, P < 0.05), and thus exhibited higher nitrogen utilization than the T6 gilts. The time-course dynamics of glucose, α-amino nitrogen, urea, lactate, and insulin levels in serum revealed that the T1 group exhibited higher utilization of nutrients after a meal than the T2 or T6 gilts. The T1 gilts also had a higher acetate content and SCFAs in feces than the T6 gilts (P < 0.05). The age, body weight and backfat thickness of the gilts at first estrous expression were not affected by the meal frequency, but the gilts in the T1 group had higher levels of serum luteinizing hormone on the 18th day of the 3rd estrus cycle and 17β-estradiol, a larger number of growing follicles and corpora lutea, and higher mRNA expression levels of genes related to follicular development on the 19th day of the 3rd estrus cycle.ConclusionsThe current findings revealed the benefits of a lower meal frequency equal feed intake on nutrient utilization and reproductive function in replacement gilts, and thus provide new insights into the nutritional strategy for replacement gilts, and the dietary pattern for other mammals, such as humans.

Perceived impact of the COVID-19 pandemic on young adults with type 1 diabetes in Rwanda.

Introductiondata on the impact of COVID-19 on people with type 1 diabetes (T1D) in less resourced countries are limited. Our study was undertaken in Kigali, Rwanda, and aimed to investigate and describe the problems and challenges experienced by young adults with T1D resulting from the early phase of the pandemic. The study further aimed to understand the mechanisms being used to solve problems and overcome challenges, and perceived support needs.Methodsthis was a cross-sectional study, with anonymous data (n=52) collected through use of questionnaire. Participants were registered, and attending or receiving diabetes-related healthcare through the Rwanda Diabetes Association clinic.Resultsmean+standard deviation age and T1D duration were 24.0±2.1 and 7.4±3.4 years respectively, with sex distribution unequal (male n=22, 42.3%). Of 43 participants, the COVID-19 pandemic did not significantly affect participants´ access to diabetes management supplies and care. Eight (18.6%) participants experienced difficulties accessing blood glucose testing strips, 13 (30.2%) insulin, and three (7.0%) syringes and pen devices. Thirty-two (74.4%) experienced difficulty in attending standard diabetes healthcare reviews at the clinic setting. Some participants experienced hardship, through a decrease in personal or family income (n=42, 80.8%) and challenges in accessing food (n=34, 65.4%), with thirty (57.7%) participants having decreased meal frequency (p<0.001).Conclusionour research illustrates the indirect effects of measures undertaken to curb the spread of COVID-19 on young adults with T1D in Rwanda. Study findings may help inform actions to mitigate negative impacts on T1D care in other crises.

Growth performance, feeding behavior, health status, and blood metabolites of environmentally heat-loaded Holstein dairy calves fed diets supplemented with chromium

We investigated the effect of Cr supplementation on growth performance, feeding behavior, health status, and blood metabolites of summer-exposed dairy calves during the pre- and postweaning periods. A total of 24 newborn Holstein female calves (1 d of age; 42.1 ± 0.89 kg of body weight) were assigned randomly to a control group (no Cr supplement; Cr-) or a Cr group (Cr+) receiving 0.05 mg of Cr/kg of body weight0.75. During the study period, the average maximum temperature-humidity index was 81.3 units, indicating a high environmental heat load. Chromium was provided in colostrum and milk during the preweaning period, and in the starter feed during the postweaning period. Calves had free access to fresh water and starter feed throughout the experiment and were weaned on d 63. Starter feed intake and total dry matter intake were greater in Cr+ calves. Despite decreased meal frequency in Cr+ calves, during the preweaning period the starter feed intake increased due to increases in meal duration and meal size and a tendency for greater meal interval. Increased postweaning starter intake in Cr+ calves was attributed to a tendency for an increase in meal duration. Chromium-supplemented calves had greater overall weight gain, but their feed efficiency and rectal temperature were not affected by Cr treatment. Chromium supplementation tended to increase the heart girth during the preweaning and overall periods and increased the hip width during the postweaning and overall periods. Respiration rates were lower in Cr+ calves than Cr- calves during the preweaning and overall periods. During the preweaning period, the time spent in eating and ruminating per 12-h period was not affected by Cr treatment. During the postweaning period, the rumination time (min per 12-h period) was unaffected but total eating time (min per 12-h period) increased in Cr+ calves. Times spent resting, drinking, standing, lying, and in nonnutritive oral behaviors were not affected by treatments during the pre- and postweaning periods. Chromium supplementation had no effects on serum concentrations of cortisol, triiodothyronine, and thyroxine measured at weaning or the end of the trial. The Cr+ calves tended to have higher serum concentrations of glucose and a higher ratio of insulin to glucose measured at the end of the trial. In conclusion, Cr supplementation of both liquid and solid feeds improved growth performance in summer-exposed calves as a result of reduced respiration rate and increased feed intake; however, no beneficial effects were found on feed efficiency and insulin metabolism.

Meal frequency and timing: impact on metabolic disease risk.

The purpose of this article is to provide an overview of the most recent human intervention trials that have examined the impact of meal frequency or meal timing on metabolic disease risk factors. Findings from intervention studies published over the past 12 months indicate that weight loss may be more pronounced with decreased meal frequency (two meals per day) versus increased meal frequency (six meals per day) under hypocaloric conditions. However, under isocaloric conditions, no effect on body weight was noted. Plasma lipid concentrations and glucoregulatory factors (fasting glucose, insulin, and insulin sensitivity) were not affected by alterations in meal frequency. As for meal timing, delaying the lunchtime meal by 3.5 h (from 1.30 p.m. to 4.30 p.m.) has no impact on body weight, but may impair glucose tolerance in young healthy adults. In sum, altering meal frequency has little impact on body weight, plasma lipids, or glucoregulatory factors, whereas eating the majority of calories later in the day may be detrimental for glycemic control. These preliminary findings, however, still require confirmation by longer term, larger scale controlled trials.

Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1

It is well-established that prostaglandins (PGs) affect tumorigenesis, and evidence indicates that PGs also are important for the reduced food intake and body weight loss, the anorexia-cachexia syndrome, in malignant cancer. However, the identity of the PGs and the PG producing cyclooxygenase (COX) species responsible for cancer anorexia-cachexia is unknown. Here, we addressed this issue by transplanting mice with a tumor that elicits anorexia. Meal pattern analysis revealed that the anorexia in the tumor-bearing mice was due to decreased meal frequency. Treatment with a non-selective COX inhibitor attenuated the anorexia, and also tumor growth. When given at manifest anorexia, non-selective COX-inhibitors restored appetite and prevented body weight loss without affecting tumor size. Despite COX-2 induction in the cerebral blood vessels of tumor-bearing mice, a selective COX-2 inhibitor had no effect on the anorexia, whereas selective COX-1 inhibition delayed its onset. Tumor growth was associated with robust increase of PGE(2) levels in plasma - a response blocked both by non-selective COX-inhibition and by selective COX-1 inhibition, but not by COX-2 inhibition. However, there was no increase in PGE(2)-levels in the cerebrospinal fluid. Neutralization of plasma PGE(2) with specific antibodies did not ameliorate the anorexia, and genetic deletion of microsomal PGE synthase-1 (mPGES-1) affected neither anorexia nor tumor growth. Furthermore, tumor-bearing mice lacking EP(4) receptors selectively in the nervous system developed anorexia. These observations suggest that COX-enzymes, most likely COX-1, are involved in cancer-elicited anorexia and weight loss, but that these phenomena occur independently of host mPGES-1, PGE(2) and neuronal EP(4) signaling.

170 THE ASSOCIATION BETWEEN MEAL FREQUENCY AND BODY FAT

Background: Obesity increases the risk for cardiovascular diseases and type 2 diabetes mellitus[1]. Many studies have revealed that increased meal frequency reduced the total serum cholesterol level, glucose tolerance and body mass index[2–4]. Hypothesizing that an increase in meal frequency decreases the percent body fat with total energy intake adjusted, we evaluated the association between meal frequency and percent body fat in Koreans aged more than 19 years old. Methods: This was cross-sectional observational study. We used the data from the Korean National Health and Nutrition Examination Survey. Percent body fat was measured with dual energy X-ray absorptiometry (DEXA). To examine the association of body fat percent with meal frequency, we performed multiple linear regression analysis adjusting for age, sex, smoking status, drinking frequency, International Physical Activity Questionnaires scores (MET-min per week), daily caloric intake (Kcal/day), and snack frequency. Results: Meal frequency was negatively associated with body fat percent (P = 0.0037). Three meal per day reduced body fat percent significantly (coefficient(95%CI) -1.578 (-2.798,-0.358)) compared than one meal per day respectively. Conclusions: These results suggest that a decreased meal frequency is associated with increased body fat percent although the causal relationship is not exactly known. It would be useful to pursue this question through further studies. References Padwal RS, Sharma AM: Prevention of cardiovascular disease: obesity, diabetes and the metabolic syndrome. Can J Cardiol 2010, 26 Suppl C:18C-20C. Ritchie LD: Less frequent eating predicts greater BMI and waist circumference in female adolescents. Am J Clin Nutr 2012. Smith KJ, Blizzard L, McNaughton SA, Gall SL, Dwyer T, Venn AJ: Daily eating frequency and cardiometabolic risk factors in young Australian adults: cross-sectional analyses. Br J Nutr 2011, [Epub ahead of print]:1-9. Jones PJ, Leitch CA, Pederson RA: Meal-frequency effects on plasma hormone concentrations and cholesterol synthesis in humans. Am J Clin Nutr 1993, 57(6):868-874.

Suppressor of cytokine signaling 3 knockdown in the mediobasal hypothalamus: counterintuitive effects on energy balance

An increase in brain suppressor of cytokine signaling 3 (SOCS3) has been implicated in the development of both leptin and insulin resistance. Socs3 mRNA is localized throughout the brain, and it remains unclear which brain areas are involved in the effect of SOCS3 levels on energy balance. We investigated the role of SOCS3 expressed in the mediobasal hypothalamus (MBH) in the development of diet-induced obesity in adult rats. Socs3 mRNA was down-regulated by local injection of adeno-associated viral vectors expressing a short hairpin directed against Socs3, after which we determined the response to high-fat high-sucrose choice diet. In contrast to neuronal Socs3 knockout mice, rats with SOCS3 knockdown limited to the MBH showed increased body weight gain, larger amounts of white adipose tissue, and higher leptin concentrations at the end of the experiment. These effects were partly due to the decrease in locomotor activity, as 24 h food intake was comparable with controls. In addition, rats with Socs3 knockdown in the MBH showed alterations in their meal patterns: average meal size in the light period was increased and was accompanied by a compensatory decrease in meal frequency in the dark phase. In addition, neuropeptide Y (Npy) mRNA levels were significantly increased in the arcuate nucleus of Socs3 knockdown rats. Since leptin is known to stimulate Npy transcription in the absence of Socs3, these data suggest that knockdown of Socs3 mRNA limited to the MBH increases Npy mRNA levels, which subsequently decreases locomotor activity and alters feeding patterns.

Measuring persistent temporomandibular joint nociception in rats and two mice strains

Temporomandibular joint (TMJ) pain has been reported to last for prolonged periods in humans. In rodents a variety of methods have been used to measure TMJ nociception, but for most of these methods the period of measurement has been minutes to a couple of hours. In addition, most measurement protocols required restraint or training of the animal. Previous studies from our laboratory demonstrated that feeding behavior, particularly meal duration, was an indicator of TMJ nociception in unrestrained and untrained male and female Sprague–Dawley rats for up to two days. In this study, we first found that injection of complete Freund's adjuvant (CFA) into the TMJ of rats significantly lengthened meal duration for 19 days and also decreased meal frequency for 42 days. Interestingly, the meal duration varied significantly from day to day within the 19 day period. TMJ interleukin-1β (IL-1β) and calcitonin gene-related peptide (CGRP) were significantly elevated in the TMJ tissues of CFA-injected animals and the level of these markers was attenuated as the meal duration decreased with time. Control animals injected with saline into the TMJ or CFA into the knee did not show a significant lengthening in meal duration but did show a decrease in meal frequency. In a second study, DBA/1LacJ mice given TMJ CFA injections showed a significantly lengthened meal duration on four of the seven days measured using end-of-the meal definition of 5 or 10 min. No other meal pattern changed significantly. Two days post-CFA injection, the DBA/1LacJ mice showed significantly elevated interleukin-6 (IL-6), but not elevated IL-1β. Seven days post-injection, both IL-6 and IL-1β were significantly elevated. No change in CGRP was detected. In this study C57Bl/6 mice also received TMJ CFA injections, but they did not show a lengthening in any meal pattern or significant increases in IL-1β, IL-6 or CGRP. Our data show, for the first time, that meal duration can be used to measure CFA-induced nociception in the TMJ over the course of several weeks in unrestrained rats and for up to seven days in the DBA/1LacJ mouse strain. In addition, C57Bl/6 mice are resistant to CFA-induced TMJ nociception at the same dose used in the DBA/1LacJ mice.

Seasonal changes of the at‐sea distribution and food provisioning in rhinoceros auklets

AbstractCentral‐place foraging seabirds increase food‐loads and decrease meal frequency when they forage in areas that are distant from the breeding colony. In 2001–2002, we studied the seasonal changes in at‐sea distribution, food‐load mass, meal frequency, and fledging mass in rhinoceros auklets (Cerorhinca monocerata), which forage in coastal waters during the day and feed their chicks at night. In both years, greater numbers of auklets were observed flying in northern waters that are more distant from the colony in June (65 km) and July (65–66 km) than in May (38–47 km). In July of both years, many auklets flew northward across the transect set 65–120 km north of the colony at sunrise; the birds returned south again at sunset, indicating that they foraged in waters outside the study area. This seasonal northward movement of the foraging area may reflect the migration of their main prey item, the Japanese anchovy (Engraulis japonicus), which move with the Tsushima Warm Current flowing from the southern Sea of Japan. Food‐load mass did not increase seasonally. In both years, the estimated daily meal frequency was lower in July than in May or June, partly because of the increased foraging distance in July. Late‐hatched chicks also displayed lighter fledging masses than early chicks in both years. We suggest that late breeders are required to forage at great distances for longer periods, which may result in decreased meal frequency and lighter fledging mass of their chicks.

Central insulin sensitivity in male and female juvenile rats

The incidence of juvenile obesity is increasing at an alarming rate. In adults, central insulin administration decreases hypothalamic orexigenic neuropeptides, food intake and body weight more effectively in males than females. Mechanisms regulating energy balance in juvenile animals are inherently different from those in adults due to differences in growth rates and hormonal milieu. Therefore, we sought to determine if central insulin treatment in juvenile rats (4 wk) would have similar sex-dependent effects on food intake as those reported in adult rats. Twenty-four hour food intake was measured following icv saline or insulin (0.01 or 0.1 U) prior to the onset of dark phase of the light cycle. An additional set of animals was used to assess the effects of central insulin on hypothalamic orexigenic (NPY, AgRP) and anorexigenic (POMC) neuropeptide mRNA expression. In both males and females, insulin reduced meal size initially (first 4 h) and later decreased meal frequency (4–24 h) to reduce cumulative food intake. Consistent with this, central insulin decreased hypothalamic NPY and AgRP and increased POMC mRNA expression. In contrast to adult studies, there were no demonstrated sex differences. These studies indicate that juvenile females and males are equally sensitive to central insulin anorexigenic effects, perhaps due to a lack of circulating gonadal hormones. The anorexigenic responsiveness of both genders suggests a potential pharmacologic approach to childhood obesity.

Ramadan Fasting Diet Entailed a Lipid Metabolic Disorder Among Type 2 Diabetic Obese Women

We designed this study to assess the effect of diet during Ramadan fasting on body weight and on serum lipid components in type 2 diabetic obese women. During Ramadan of 2005, 89 diabetic women receiving oral treatment (BMI = 33.20±3.01 kg m-2), aged 52 (±5 years), were selected. The study was carried out over 3 periods-, before (T1: pre-fasting), during (T2: fasting), and after (T3: post-fasting) Ramadan-in Sidi-bel-Abbes city. The daily food intake during the course of 3 days was recorded, and then weight, height, waist and hip circumferences, Body Mass Index (BMI) and Waist to Hip Ratio (WHR) were measured. Blood samples were analyzed for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), apolipoprotein A1 (apoA-I), apolipoprotein B (apoB), triglycerides (TGs), fasting serum glucose (FSG), and glycated haemoglobin (HbA1c) and results were compared using Student’s t-test. The dietary fat consumption increased during Ramadan, especially for the saturated one and as a result induced a major lipid unbalance, marked by a disorder observed in nearly all of the serum lipid components. There was a significant weight loss in diabetic women (-2.56 kg, p<0.05) during T2, correlated with a decrease in meal frequency (r2 = 0.313, p<0.01). As well, the level of glucose decreased significantly during T2 (8.23±0.75 mmol L-1) compared to T1 (9.23±1.08 mmol L-1). Our study showed a significant weight loss during Ramadan period and an improvement of glucose homeostasis. However, the lipid metabolism was imbalanced and was strongly linked to the Ramadan diet and to the eating habits modification.

Effect of Ramadan fasting on anthropometric parameters and food consumption in 276 type 2 diabetic obese women

AIM:To assess the effect of Ramadan fasting on body weight and food consumption in type 2 diabetic obese women.MATERIALS AND METHODS:A total of 276 outpatient women receiving oral antidiabetic drugs (OADs) (BMI = 34.63 ± 3.29 kg/m2), aged 49 (±6 years), were selected. The study was carried out over three periods - before (T1: prefasting), during (T2: fasting), and after (T3: postfasting) Ramadan - in three towns located in the northwestern region of Algeria. During the course of 3 days, the daily food intake and anthropometric parameters weight, height, waist and hip circumferences, body mass index (BMI), and waist-hip ratio (WHR) were recorded. A one-way repeated measures ANOVA test was used to compare the groups.RESULTS:The main effect of fasting during Ramadan was a significant weight loss (−3.12 kg i.e. 3.70%; P < 0.01), a decrease in meal frequency (2.2 ± 0.3 vs. 4.3 ± 0.4) as well as in energy intake (1488 ± 118 vs.1823 ± 262 Kcal/d) and an important increase in dietary fat consumption (35.84 vs. 25.36%), especially the saturated one (231Kca/d i.e. 43.25%) of total fat, dietary cholesterol (392 ± 121 vs. 221 ± 73 mg/d), and polyunsaturated fatty acids (PUFA). Except in three cases, there were no frequent hypoglycaemic episodes observed among the participants.CONCLUSIONS:Fasting during the month of Ramadan causes weight loss and decrease in calorie intake, which is correlated with a decrease in meal frequency. However, more foods rich in fat and dietary cholesterol were consumed during this period. The latter could constitute a high risk for diabetics who are fasting, in particular when medication advice and/or health care control are insufficient or ignored.

Starvation after AgRP neuron ablation is independent of melanocortin signaling

Ablation of inhibitory agouti-related protein (AgRP)-expressing neurons in the arcuate nucleus that also synthesize gamma-amino-butyric acid (GABA) and neuropeptide Y in adult mice leads to starvation within 1 week. The removal of inhibition from the AgRP neurons onto neighboring proopiomelanocortin neurons and their common postsynaptic neurons is predicted to stimulate melanocortin signaling, which is known to inhibit appetite. To examine the importance of uncontrolled melanocortin signaling in mediating starvation in this model, we ablated AgRP neurons in A(y)/a mice that have chronic blockade of the melanocortin signaling. The blockade of melanocortin signaling did not ameliorate the rate of starvation. On both WT and A(y)/a genetic backgrounds, there was a progressive decrease in meal frequency after AgRP neuron ablation. Surprisingly, intraoral feeding also was dramatically reduced after the ablation of AgRP neurons. These results indicate that both the appetitive and consummatory aspects of feeding become impaired in a melanocortin-independent manner after AgRP neuron ablation.

Factors Contributing to Obesity in Bombesin Receptor Subtype-3-Deficient Mice

Mice with a targeted disruption of bombesin receptor subtype-3 (BRS-3 KO) develop hyperphagia, obesity, hypertension, and impaired glucose metabolism. However, the factors contributing to their phenotype have not been clearly established. To determine whether their obesity is a result of increased food intake or a defect in energy regulation, we matched the caloric intake of BRS-3 KO mice to wild-type (WT) ad libitum (ad lib)-fed controls over 21 wk. Although BRS-3 KO ad lib-fed mice were 29% heavier, the body weights of BRS-3 KO pair-fed mice did not differ from WT ad lib-fed mice. Pair-feeding BRS-3 KO mice normalized plasma insulin but failed to completely reverse increased adiposity and leptin levels. Hyperphagia in ad lib-fed KO mice was due to an increase in meal size without a compensatory decrease in meal frequency resulting in an increase in total daily food intake. An examination of neuropeptide Y, proopiomelanocortin, and agouti-related peptide gene expression in the arcuate nucleus revealed that BRS-3 KO mice have some deficits in their response to energy regulatory signals. An evaluation of the satiety effects of cholecystokinin, bombesin, and gastrin-releasing peptide found no differences in feeding suppression by these peptides. We conclude that hyperphagia is a major factor leading to increased body weight and hyperinsulinemia in BRS-3 KO mice. However, our finding that pair-feeding did not completely normalize fat distribution and plasma leptin levels suggests there is also a metabolic dysregulation that may contribute to, or sustain, their obese phenotype.

CCK 1 receptor is essential for normal meal patterning in mice fed high fat diet

Cholecystokinin (CCK), released by lipid in the intestine, initiates satiety by acting at cholecystokinin type 1 receptors (CCK 1Rs) located on vagal afferent nerve terminals located in the wall of the gastrointestinal tract. In the present study, we determined the role of the CCK 1R in the short term effects of a high fat diet on daily food intake and meal patterns using mice in which the CCK 1R gene is deleted. CCK 1R −/− and CCK 1R +/+ mice were fed isocaloric high fat (HF) or low fat (LF) diets ad libitum for 18 h each day and meal size, meal frequency, intermeal interval, and meal duration were determined. Daily food intake was unaltered by diet in the CCK 1R −/− compared to CCK 1R +/+ mice. However, meal size was larger in the CCK 1R −/− mice compared to CCK 1R +/+ mice when fed a HF diet, with a concomitant decrease in meal frequency. Meal duration was increased in mice fed HF diet regardless of phenotype. In addition, CCK 1R −/− mice fed a HF diet had a 75% decrease in the time to 1st meal compared to CCK 1R +/+ mice following a 6 h fast. These data suggest that lack of the CCK 1R results in diminished satiation, causing altered meal patterns including larger, less frequent meals when fed a high fat diet. These results suggest that the CCK 1R is involved in regulating caloric intake on a meal to meal basis, but that other factors are responsible for regulation of daily food intake.

Hyperphagia and obesity in OLETF rats lacking CCK-1 receptors

The brain-gut peptide cholecystokinin (CCK) inhibits food intake following peripheral or site directed central administration. Peripheral exogenous CCK inhibits food intake by reducing the size and duration of a meal. Antagonist studies have demonstrated that the actions of the exogenous peptide mimic those of endogenous CCK. Antagonist administration results in increased meal size and meal duration. The feeding inhibitory actions of CCK are mediated through interactions with CCK-1 receptors. The recent identification of the Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat as a spontaneous CCK-1 receptor knockout model has allowed a more comprehensive evaluation of the feeding actions of CCK. OLETF rats become obese and develop non-insulin dependent diabetes mellitus (NIDDM). Consistent with the absence of CCK-1 receptors, OLETF rats do not respond to exogenous CCK. OLETF rats are hyperphagic and their increased food intake is characterized by a large increase in meal size with a decrease in meal frequency that is not sufficient to compensate for the meal size increase. Deficits in meal size control are evident in OLETF rats as young as 2 days of age. OLETF obesity is secondary to the increased food intake. Pair feeding to amounts consumed by intact control rats normalizes body weight, body fat and elevated insulin and glucose levels. Hypothalamic arcuate nucleus peptide mRNA expression in OLETF rats is appropriate to their obesity and is normalized by pair feeding. In contrast, pair fed and young pre-obese OLETF rats have greatly elevated dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) mRNA expression. Elevated DMH NPY in OLETF rats appears to be a consequence of the absence of CCK-1 receptors. In intact rats NPY and CCK-1 receptors colocalize to neurons within the compact subregion of the DMH and local CCK administration reduces food intake and decreases DMH NPY mRNA expression. We have proposed that the absence of DMH CCK-1 receptors significantly contributes to the OLETF's inability to compensate for their meal size control deficit leading to their overall hyperphagia. Access to a running wheel and the resulting exercise normalizes food intake and body weight in OLETF rats. When given access to running wheels for 6 weeks shortly after weaning, OLETF rats do not gain weight to the same degree as sedentary OLETF rats and do not develop NIDDM. Exercise also prevents elevated levels of DMH NPY mRNA expression, suggesting that exercise exerts an alternative, non-CCK mediated, control on DMH NPY. The OLETF rat is a valuable model for characterizing actions of CCK in energy balance and has provided novel insights into interactions between exercise and food intake.

Increased short-term food satiation and sensitivity to cholecystokinin in neurotrophin-4 knock-in mice.

Neurotrophin-4 (NT-4) knockout mice exhibited decreased innervation of the small intestine by vagal intraganglionic laminar endings (IGLEs) and reduced food satiation. Recent findings suggested this innervation was increased in NT-4 knock-in (NT-4KI) mice. Therefore, to further investigate the relationship between intestinal IGLEs and satiation, meal patterns were characterized using solid and liquid diets, and cholecystokinin (CCK) effects on 30-min solid diet intake were examined in NT-4KI and wild-type mice. NT-4KI mice consuming the solid diet exhibited reduced meal size, suggesting increased satiation. However, compensation occurred through increased meal frequency, maintaining daily food intake and body weight gain similar to controls. Mutants fed the liquid diet displayed a decrease in intake rate, again implying increased satiation, but meal duration increased, which led to an increase in meal size. This was compensated for by decreased meal frequency, resulting in similar daily food intake and weight gain as controls. Importantly, these alterations in NT-4KI mice were opposite, or different, from those of NT-4 knockout mice, further supporting the hypothesis that they are specific to vagal afferent signaling. CCK suppressed short-term intake in mutants and controls, but the mutants exhibited larger suppressions at lower doses, implying they were more sensitive to CCK. Moreover, devazepide prevented this suppression, indicating this increased sensitivity was mediated by CCK-1 receptors. These results suggest that the NT-4 gene knock-in, probably involving increased intestinal IGLE innervation, altered short-term feeding, in particular by enhancing satiation and sensitivity to CCK, whereas long-term control of daily intake and body weight was unaffected.

Suppression of feed intake after parenteral administration of D-beta-hydroxybutyrate in pygmy goats.

The effect of intraperitoneal injection of D,L- or D-beta-hydroxybutyrate on feed intake and plasma metabolites was investigated in pygmy goats. The combined intraperitoneal injection of D,L-beta-hydroxybutyrate or D-beta-hydroxybutyrate (15 mmol/kg0.75) and 1,3-butanediol (6.6 mmol/kg0.75), a ketogenic substrate, decreased cumulative food intake while the same dose of 1,3-butanediol or DL-beta-hydroxybutyrate alone had no effect. The decrease in food intake after combined injection of D-beta-hydroxybutyrate and 1,3-butanediol was characterized by a significant decrease in meal frequency and a prolongation of the latency to eat. The hypophagic effect of the combined injection of D-beta-hydroxybutyrate and 1,3-butanediol was significant for 8 h, while the hypophagia after D,L-beta-hydroxybutyrate and 1,3-butanediol was significant for only 2 h after injection. Injection of D,L-beta-hydroxybutyrate increased plasma D-beta-hydroxybutyrate levels to 0.55 mmol/l and decreased plasma free fatty acids. Addition of 1,3-butanediol (6.6 mmol/kg0.75) to the injection increased plasma D-beta-hydroxybutyrate level up to 0.75 mmol/l. The results show that parenteral administration of D-hydroxybutyrate reduces feed intake in pygmy goats and that the hypophagia appears to be related to the amount of D-beta-hydroxybutyrate injected. The hypophagia seems to be related to elevated plasma D-beta-hydroxybutyrate concentration, and the threshold concentration appeared to be about 0.7 mmol/l under the experimental conditions of this study.