Regulation Of Caloric Intake Research Articles

Food Intake is Influenced by Gastric Emptying, Motility, and Compliance

Obesity, which results from an increase in caloric intake relative to energy expenditure, is often associated with an alterations in gastric emptying. The exact relationship between gastric emptying and food intake, however, is unclear. Some reports have suggested that obesity is associated with an accelerated liquid but a delayed solid gastric emptying rate, while more recent studies have suggested that there may be no significant correlation between BMI and gastric emptying. The purpose of the present study is to test the hypothesis that food intake in rodents is influenced by a combination of gastric emptying, gastric tone and motility, and compliance.Male and female Sprague‐Dawley rats (4–8 weeks of age) were fed a control or HFD (14% or 60% kcal from fat, respectively) for 3–5 days prior to experimentation (acute HFD). Food intake and body weight were measured twice daily prior to, and throughout, HFD exposure. The 13C octanoic acid breath test was used to measure gastric emptying rates in rats repeatedly throughout exposure to the high fat diet. Miniature strain gauges were sewn onto the ventral surface of the corpus and the antrum of the stomach in anesthetized rats to allow measurement of basal gastric motility and tone. Gastric compliance was measured via a latex balloon inserted into the stomach via the pylorus in anesthetized rats. Following placement, the balloon was maximally inflated (2mL; 1min) before deflation. After 10min recovery, the balloon was then inflated in 0.2mL increments for 1 minute each, and the balloon pressure measured continuously.Acute high fat diet exposure induced a brief (24hr) period of hyperphagia before rats regulate their food intake and restore caloric balance within a 3–5 day period (74.7±4.0 kcal/day at day 1 vs. 59±3.7 kcal/day at days 3–5, P<0.05, N=16), as described previously (PMID: 29368945). While gastric emptying rate was not significantly different during the hyperphagic period following high fat diet exposure (120±14.1% of baseline, P>0.05, N=6), emptying was significantly delayed after 4 days HFD exposure (144±15.8% of baseline, P>0.05, N=6), when caloric intake is restored to baseline levels. Neither gastric compliance (total AUC throughout distention volume range: 37±1.7 vs. 38±1.1, P>0.05, N=6–8) nor basal gastric motility (104±12.2 vs. 110±16.3mg/min P>0.05, N=10–13) was altered during this time period.These data suggest that i) gastric emptying rates are more closely associated with the regulation of caloric intake and energy balance than either basal gastric motility or compliance, and ii) gastric emptying may be disrupted without any observed alterations in local gastric functions. We have shown previously, that restoration of caloric balance is associated with neuroplasticity within central vagal neurocircuits (PMID: 29368945). These data suggest that dysregulation of gastric emptying may be important in the central control of food intake, even under conditions where alterations in peripheral gastric functions, including motility and compliance, are not observed.Support or Funding InformationNIH DK111667 to KNB NIH F31 118833 to CC

Dietary fats promote functional and structural changes in the median eminence blood/spinal fluid interface\u2014the protective role for BDNF

BackgroundThe consumption of large amounts of dietary fats activates an inflammatory response in the hypothalamus, damaging key neurons involved in the regulation of caloric intake and energy expenditure. It is currently unknown why the mediobasal hypothalamus is the main target of diet-induced brain inflammation. We hypothesized that dietary fats can damage the median eminence blood/spinal fluid interface.MethodsSwiss mice were fed on a high-fat diet, and molecular and structural studies were performed employing real-time PCR, immunoblot, immunofluorescence, transmission electron microscopy, and metabolic measurements.ResultsThe consumption of a high fat diet was sufficient to increase the expression of inflammatory cytokines and brain-derived neurotrophic factor in the median eminence, preceding changes in other circumventricular regions. In addition, it led to an early loss of the structural organization of the median eminence β1-tanycytes. This was accompanied by an increase in the hypothalamic expression of brain-derived neurotrophic factor. The immunoneutralization of brain-derived neurotrophic factor worsened diet-induced functional damage of the median eminence blood/spinal fluid interface, increased diet-induced hypothalamic inflammation, and increased body mass gain.ConclusionsThe median eminence/spinal fluid interface is affected at the functional and structural levels early after introduction of a high-fat diet. Brain-derived neurotrophic factor provides an early protection against damage, which is lost upon a persisting consumption of large amounts of dietary fats.

The Effect of Nonnutritive Sweeteners Added to a Liquid Diet on Volume and Caloric Intake and Weight Gain in Rats.

Long-term effects of diet beverage consumption on the regulation of caloric intake is unclear. The goal of this study was to investigate whether the chronic intake of a liquid diet with nonnutritive sweeteners (NNS) would lead to greater appetite and weight gain. Wistar rats were fed a liquid diet (Osmolite) sweetened with nutritive sweetener (NS; sucrose) and NNS (stevia and saccharin) or a nonsweetened control. Intakes and weight gain were measured. Phases 1 and 2 investigated sweetness preference, phase 3 used diets with or without sweeteners, and phase 4 measured the effect on volume of food and caloric intake of alternating between NNS, NS, and control diets. In phase 1, rats preferred: stevia, 0.10%; saccharin, 0.20%; and sucrose, 15%. In phase 2, rats preferred the sweetened diet over the control. In phase 3, rats fed the NS diet consumed less volume and more calories but gained less weight. In phase 4, when altering diet from NNS to NS, no differences were observed in appetite or weight gain. Using sucrose-sweetened diet as a control, increased weight gain with the ingestion of NNS was observed. However, using a nonsweetened control, neither increased caloric intake nor weight gain occurred with NNS intake. Alternating diets between NNS, NS, and control did not affect the appetite.

Serotonin enhances the impact of health information on food choice

Serotonin has been implicated in promoting self-control, regulation of hunger and physiological homeostasis, and regulation of caloric intake. However, it remains unclear whether the effects of serotonin on caloric intake reflect purely homeostatic mechanisms, or whether serotonin also modulates cognitive processes involved in dietary decision making. We investigated the effects of an acute dose of the serotonin reuptake inhibitor citalopram on choices between food items that differed along taste and health attributes, compared with placebo and the noradrenaline reuptake inhibitor atomoxetine. Twenty-seven participants attended three sessions and received single doses of atomoxetine, citalopram, and placebo in a double-blind randomised cross-over design. Relative to placebo, citalopram increased choices of more healthy foods over less healthy foods. Citalopram also increased the emphasis on health considerations in decisions. Atomoxetine did not affect decision making relative to placebo. The results support the hypothesis that serotonin may influence food choice by enhancing a focus on long-term goals. The findings are relevant for understanding decisions about food consumption and also for treating health conditions such as eating disorders and obesity.

Melanin-Concentrating Hormone and Its MCH-1 Receptor: Relationship Between Effects on Alcohol and Caloric Intake.

Reward and energy homeostasis are both regulated by a network of hypothalamic neuropeptide systems. The melanin-concentrating hormone (MCH) and its MCH-1 receptor (MCH1-R) modulate alcohol intake, but it remains unknown to what extent this reflects actions on energy balance or reward. Here, we evaluated the MCH1-R in regulation of caloric intake and motivation to consume alcohol in states of escalated consumption. Rats had intermittent access (IA) to alcohol and were divided into high- and low-drinking groups. Food and alcohol consumption was assessed after administration of an MCH1-R antagonist, GW803430. Next, GW803430 was evaluated on alcohol self-administration in protracted abstinence induced by IA in high-drinking rats. Finally, the effect of GW803430 was assessed on alcohol self-administration in acute withdrawal in rats exposed to alcohol vapor. Gene expression of MCH and MCH1-R was measured in the hypothalamus and nucleus accumbens (NAc) in both acute and protracted abstinence. High-drinking IA rats consumed more calories from alcohol than chow and GW803430 decreased both chow and alcohol intake. In low-drinking rats, only food intake was affected. In protracted abstinence from IA, alcohol self-administration was significantly reduced by pretreatment with GW803430 and gene expression of both MCH and the MCH1-R were dysregulated in hypothalamus and NAc. In contrast, during acute withdrawal from vapor exposure, treatment with GW803430 did not affect alcohol self-administration, and no changes in MCH or MCH1-R gene expression were observed. Our data suggest a dual role of MCH and the MCH1-R in regulation of alcohol intake, possibly through mechanisms involving caloric intake and reward motivation. A selective suppression of alcohol self-administration during protracted abstinence by GW803430 was observed and accompanied by adaptations in gene expression of MCH and MCH1-R. Selective suppression of escalated consumption renders the MCH1-R an attractive target for treatment of alcohol use disorders.

Genetic Deletion and Pharmacological Inhibition of Phosphodiesterase 10A Protects Mice From Diet-Induced Obesity and Insulin Resistance

Phosphodiesterase 10A (PDE10A) is a novel therapeutic target for the treatment of schizophrenia. Here we report a novel role of PDE10A in the regulation of caloric intake and energy homeostasis. PDE10A-deficient mice are resistant to diet-induced obesity (DIO) and associated metabolic disturbances. Inhibition of weight gain is due to hypophagia after mice are fed a highly palatable diet rich in fats and sugar but not a standard diet. PDE10A deficiency produces a decrease in caloric intake without affecting meal frequency, daytime versus nighttime feeding behavior, or locomotor activity. We tested THPP-6, a small molecule PDE10A inhibitor, in DIO mice. THPP-6 treatment resulted in decreased food intake, body weight loss, and reduced adiposity at doses that produced antipsychotic efficacy in behavioral models. We show that PDE10A inhibition increased whole-body energy expenditure in DIO mice fed a Western-style diet, achieving weight loss and reducing adiposity beyond the extent seen with food restriction alone. Therefore, chronic THPP-6 treatment conferred improved insulin sensitivity and reversed hyperinsulinemia. These data demonstrate that PDE10A inhibition represents a novel antipsychotic target that may have additional metabolic benefits over current medications for schizophrenia by suppressing food intake, alleviating weight gain, and reducing the risk for the development of diabetes.

Taste receptor signaling in the mammalian gut

Molecular sensing by gastrointestinal (GI) cells plays a crucial role in the control of multiple fundamental functions including digestion, regulation of caloric intake, pancreatic insulin secretion, and metabolism, as well as protection from ingested harmful drugs and toxins. These processes are likely to be mediated by the initiation of humoral and/or neural pathways through the activation of endocrine cells. However, the initial recognition events and mechanism(s) involved are still largely unknown. This article reviews the current evidence that the chemosensory machinery discovered in specialized neuroepithelial taste receptor cells of the lingual epithelium is operational in enteroendocrine open GI cells that sense the chemical composition of the luminal contents of the gut.

Effects of Metabolizable Energy and Amino Acid Levels on Turkey Performance from Hatch to Marketing

Two experiments were conducted with growing turkeys from hatch to market examining the performance at various dietary energy and amino acid (AA) levels as well as the relationship between energy and essential amino acids at these energy levels. The results of the first experiment indicated that increasing ME alone improved feed efficiency (FE); however, it did not affect BW in either toms or hens. In addition, increasing ME alone resulted in better regulation of caloric intake (CI) in toms than in hens. The caloric efficiency (CE) (BW/CI) improved with the higherenergy diets. In a second experiment both AA and ME levels were changed. Using 95% of NRC amino acid levels depressed performance, whereas turkeys receiving 105 and 110% of the recommended AA levels had improved BW and FE until 6 wk. From 7 to 19 wk, increasing dietary AA levels decreased feed intake (FI). Increasing both AA and ME together did not, in all cases, produce the same effect as altering their levels independently.

Interaction of TRH and CCK in the satiation of alcohol intake

Thyrotropin-releasing hormone (TRH) and cholecystokinin octapeptide (CCK) are endogenous neuropeptides known to inhibit intake of alcohol. Although both peptides are released by alcohol consumption and are hypothesized to satiate alcohol intake, their interaction has not been examined. We deprived ad-lib-fed male ( n=6) and female ( n=4) Wistar rats of water for 23 h and then gave them 30 min access to 5% w/v ethanol, followed by 30 min access to water. After adaptation to this schedule, rats were randomly assigned to receive intraperitoneal injections of either saline+saline, CCK (4 μg/kg)+saline, saline+TRH (10 mg/kg) or CCK+TRH immediately before alcohol access. Analyses of variance revealed a significant ( P<.05) effect of CCK, and a significant interaction of CCK and TRH in control of ethanol consumption. CCK reliably reduced alcohol intake, and TRH blocked this satiation effect of CCK, increasing intake by 88.8% and 34.6% in males and females, respectively. TRH increased water intake in females, and CCK blocked this effect of TRH. Results indicate an infra-dose-additive interaction of CCK and TRH in satiation of alcohol intake, which may reflect a natural, endogenous neuropeptide interaction in the regulation of caloric intake.

Impact of acute corticosterone administration on feeding and macronutrient self-selection patterns.

Food intake, body weight, and meal patterns in rats are known to be specifically influenced by circulating corticosterone (CORT). The present study examined, in Sprague-Dawley rats, the role of CORT in the regulation of caloric intake and choice of macronutrients during specific periods of the light-dark cycle. Adrenalectomy (ADX) significantly attenuated the ingestion of all three macronutrients, namely, protein, carbohydrate, and fat, in different test periods of the light-dark cycle. This deficit was significantly stronger just before or during the early dark hours, compared with the light period, and it was immediately CORT reversible. During this same early dark period, the stimulatory effect of CORT (0.5 or 2.0 mg/kg sc) on total food intake in ADX animals was also significantly stronger than during the light period. At this time, the CORT-injected ADX animals consumed an even greater amount of total food intake than did the vehicle-injected sham-operated animals and showed a significant preference for carbohydrate, as opposed to no change or a decline in preference for protein or fat. These findings, in light of other evidence, suggest that CORT ensures and stabilizes the ingestion of all three macronutrients but, in particular, stimulates carbohydrate ingestion during the important feeding period at the dark onset when CORT levels normally peak. It is proposed that CORT may provide a critical signal, in conjunction with hypothalamic neurotransmitter systems, in the behavioral and metabolic regulation of body energy balance.

Resistance to diet-induced obesity: food intake, pancreatic sympathetic tone, and insulin.

After 15 wk on a moderately high-calorie high-fat (CM) diet, 43% of 40 3-mo-old male Sprague-Dawley rats developed diet-induced obesity (DIO) (29% more weight gain), whereas 57% of diet-resistant (DR) rats gained no more weight than 20 chow-fed controls. When switched to chow for another 7 wk, DR rats ate 13% less, gained 55% less weight, and had 49% lower food efficiency, whereas DIO rats ate 4% less but had comparable weight gain and efficiency to controls. DIO rats had 29% more carcass lipid (percent of carcass weight). DIO rat retroperitoneal white adipose pads had 65% more cells that were the same size as those in chow-fed pads; DR rat cells were similar to controls. Both DR and DIO rats increased norepinephrine turnover in their interscapular brown adipose pads by greater than 90%. DIO rats also had 40% lower pancreatic turnover; their plasma insulin levels were 327% of controls after 15 wk on the CM diet and 188% after 7 wk on chow. DR levels were the same as controls at both times. Therefore, regulation of caloric intake, pancreatic sympathetic tone, and plasma insulin levels were three important differences between rats that resisted and those that developed DIO on high-energy diets.

Metabolic Obesity?

For the adipose tissues of an animal or a human being to increase, more calories must be ingested and absorbed than are needed to satisfy the organism's metabolic requirements. In normal persons, there is a close coupling between metabolic demands and caloric intake, so that weight normally remains relatively constant in adults. Many reasons for disturbances in regulation of caloric intake are fairly well understood. These causes include damage to the hypothalamic satiety center, certain types of emotional disturbances, socially established patterns of eating, persistent high caloric intake in persons whose needs have lessened as a result of alterations in . . .

Sexual dimorphism in the regulation of caloric intake and body weight of rats fed different diets

Female, androgenized female (AF), and male rats were given access to 1 of 3 diets—chow (C), high-dextrose (D-chow:dextrose, 2:1), and high-fat (F-chow:Crisco, 2:1) for 2 months. Caloric intake (CI), water intake, and body weights were monitored daily. Responses to gonadectomy and a single injection of estradiol benzoate (EB) were also studied. For females, F- and C-fed rats had comparable CI's, whereas D-fed rats chronically ate much less. For males, F-fed rats overate, whereas C- and D-fed rats had comparable CI's. The pattern of CI of AF rats fed the 3 diets was intermediate between that of males and females. Male rats were less responsive to the anorexic effects of EB than were the other two groups, and the F-diet potentiated the anorexic effects of EB in all three groups. Results are discussed in terms of a sex difference in the hypothalamic regulation of feeding behavior which is modulated by gonadal hormones.

Regulation of caloric intake in yellow mice (C57BL/6J-A y/a)

The ability of yellow and normal black mice to reduce food intake when given surplus calories was studied to elucidate the mechanisms responsible for hyperphagia in yellow mice. When given sugar solutions to drink, immature (6–7 weeks old) yellow mice increased total caloric intake more than did lean control mice. Older (11–14 weeks) yellow mice were similar to control mice. The oldest yellow mice tested (25–33 weeks) increased total caloric intake less than lean control mice, when given sugar solutions. In contrast, yellow mice of all ages increased total caloric intake more than lean mice when given corn oil. Yellow mice had similar or lower preference for sugar and oil calories than did black mice.