Deletion of the Clock Gene Bmal2 Leads to Alterations in Hypothalamic Clocks, Circadian Regulation of Feeding, and Energy Balance.

BMAL2 (ARNTL2) is a paralog of BMAL1 that can form heterodimers with the other circadian factors CLOCK and NPAS2 to activate transcription of clock and clock-controlled genes. To assess a possible role of Bmal2 in the circadian regulation of metabolism, we investigated daily variations of energy metabolism, feeding behavior, and locomotor behavior, as well as ability to anticipate restricted food access in male mice knock-out for Bmal2 (B2KO). While their amount of food intake and locomotor activity were normal compared with wild-type mice, B2KO mice displayed increased adiposity (1.5-fold higher) and fasted hyperinsulinemia (fourfold higher) and tended to have lower energy expenditure at night. Impairment of the master clock in the suprachiasmatic nuclei was evidenced by the shorter free-running period (-14 min/cycle) of B2KO mice compared with wild-type controls and by a loss of daily rhythmicity in expression of intracellular metabolic regulators (e.g., Lipoprotein lipase and Uncoupling protein 2). The circadian window of eating was longer in B2KO mice. The circadian patterns of food intake and meal numbers were bimodal in control mice but not in B2KO mice. In response to restricted feeding, food-anticipatory activity was almost prevented in B2KO mice, suggesting altered food clock that controls anticipation of food availability. In the mediobasal hypothalamus of B2KO mice, expression of genes coding orexigenic neuropeptides (including Neuropeptide y and Agouti-Related Peptide) was downregulated, while Lipoprotein lipase expression lost its rhythmicity. Together, these data highlight that BMAL2 has major impacts on brain regulation of metabolic rhythms, sleep-wake cycle, and food anticipation.

Conditional Deletion of ß-Catenin in the Mediobasal Hypothalamus Impairs Adaptive Energy Expenditure in Response to High-Fat Diet and Exacerbates Diet-Induced Obesity.

ß-Catenin is a bifunctional molecule that is an effector of the wingless-related integration site (Wnt) signaling to control gene expression and contributes to the regulation of cytoskeleton and neurotransmitter vesicle trafficking. In its former role, ß-catenin binds transcription factor 7-like 2 (TCF7L2), which shows strong genetic associations with the pathogenesis of obesity and type-2 diabetes. Here, we sought to determine whether ß-catenin plays a role in the neuroendocrine regulation of body weight and glucose homeostasis. Bilateral injections of adeno-associated virus type-2 (AAV2)-mCherry-Cre were placed into the arcuate nucleus of adult male and female ß-catenin flox mice, to specifically delete ß-catenin expression in the mediobasal hypothalamus (MBH-ß-cat KO). Metabolic parameters were then monitored under conditions of low-fat (LFD) and high-fat diet (HFD). On LFD, MBH-ß-cat KO mice showed minimal metabolic disturbances, but on HFD, despite having only a small difference in weekly caloric intake, the MBH-ß-cat KO mice were significantly heavier than the control mice in both sexes (p < 0.05). This deficit seemed to be due to a failure to show an adaptive increase in energy expenditure seen in controls, which served to offset the increased calories by HFD. Both male and female MBH-ß-cat KO mice were highly glucose intolerant when on HFD and displayed a significant reduction in both leptin and insulin sensitivity compared with controls. This study highlights a critical role for ß-catenin in the hypothalamic circuits regulating body weight and glucose homeostasis and reveals potential mechanisms by which genetic variation in this pathway could impact on development of metabolic disease.

Pharmacological Advances in Incretin-Based Polyagonism: What We Know and What We Don't.

The prevalence of obesity continues to rise in both adolescents and adults, in parallel obesity is strongly associated with the increased incidence of type 2 diabetes, heart failure, certain types of cancer, and all-cause mortality. In relation to obesity, many pharmacological approaches of the past have tried and failed to combat the rising obesity epidemic, particularly due to insufficient efficacy or unacceptable side effects. However, while the history of antiobesity medication is plagued by failures and disappointments, we have witnessed over the last 10 years substantial progress, particularly in regard to biochemically optimized agonists at the receptor for glucagon-like peptide-1 (GLP-1R) and unimolecular coagonists at the receptors for GLP-1 and the glucose-dependent insulinotropic polypeptide (GIP). Although the GIP receptor:GLP-1R coagonists are being heralded as premier pharmacological tools for the treatment of obesity and diabetes, uncertainty remains as to why these drugs testify superiority over best-in-class GLP-1R monoagonists. Particularly with regard to GIP, there remains great uncertainty if and how GIP acts on systems metabolism and if the GIP system should be activated or inhibited to improve metabolic outcome in adjunct to GLP-1R agonism. In this review, we summarize recent advances in GLP-1- and GIP-based pharmacology and discuss recent findings and open questions related to how the GIP system affects systemic energy and glucose metabolism.

Exercise-induced increase in muscle insulin sensitivity in men is amplified when assessed using a meal test.

AIMS/HYPOTHESIS: Exercise has a profound effect on insulin sensitivity in skeletal muscle. The euglycaemic-hyperinsulinaemic clamp (EHC) is the gold standard for assessment of insulin sensitivity but it does not reflect the hyperglycaemia that occurs after eating a meal. In previous EHC investigations, it has been shown that the interstitial glucose concentration in muscle is decreased to a larger extent in previously exercised muscle than in rested muscle. This suggests that previously exercised muscle may increase its glucose uptake more than rested muscle if glucose supply is increased by hyperglycaemia. Therefore, we hypothesised that the exercise-induced increase in muscle insulin sensitivity would appear greater after eating a meal than previously observed with the EHC. METHODS: Ten recreationally active men performed dynamic one-legged knee extensor exercise for 1 h. Following this, both femoral veins and one femoral artery were cannulated. Subsequently, 4 h after exercise, a solid meal followed by two liquid meals were ingested over 1 h and glucose uptake in the two legs was measured for 3 h. Muscle biopsies from both legs were obtained before the meal test and 90 min after the meal test was initiated. Data obtained in previous studies using the EHC (n=106 participants from 13 EHC studies) were used for comparison with the meal-test data obtained in this study. RESULTS: Plasma glucose and insulin peaked 45 min after initiation of the meal test. Following the meal test, leg glucose uptake and glucose clearance increased twice as much in the exercised leg than in the rested leg; this difference is twice as big as that observed in previous investigations using EHCs. Glucose uptake in the rested leg plateaued after 15 min, alongside elevated muscle glucose 6-phosphate levels, suggestive of compromised muscle glucose metabolism. In contrast, glucose uptake in the exercised leg plateaued 45 min after initiation of the meal test and there were no signs of compromised glucose metabolism. Phosphorylation of the TBC1 domain family member 4 (TBC1D4; p-TBC1D4Ser704) and glycogen synthase activity were greater in the exercised leg compared with the rested leg. Muscle interstitial glucose concentration increased with ingestion of meals, although it was 16% lower in the exercised leg than in the rested leg. CONCLUSIONS/INTERPRETATION: Hyperglycaemia after meal ingestion results in larger differences in muscle glucose uptake between rested and exercised muscle than previously observed during EHCs. These findings indicate that the ability of exercise to increase insulin-stimulated muscle glucose uptake is even greater when evaluated with a meal test than has previously been shown with EHCs.

Circadian patterns of behaviour change during pregnancy in mice.

Food intake and activity adapt during pregnancy to meet the increased energy demands. In comparison to non-pregnant females, pregnant mice consume more food, eating larger meals during the light phase, and reduce physical activity. How pregnancy changes the circadian timing of behaviour was less clear. We therefore randomised female C57BL/6J mice to mating for study until early (n = 10), mid- (n = 10) or late pregnancy (n = 11) or as age-matched, non-pregnant controls (n = 12). Mice were housed individually in Promethion cages with a 12 h light-12 h dark cycle [lights on at 07.00 h, Zeitgeber (ZT)0] for behavioural analysis. Food intake between ZT10 and ZT11 was greater in pregnant than non-pregnant mice on days 6.5-12.5 and 12.5-17.5. In mice that exhibited a peak in the last 4 h of the light phase (ZT8-ZT12), peaks were delayed by 1.6 h in the pregnant compared with the non-pregnant group. Food intake immediately after dark-phase onset (ZT13-ZT14) was greater in the pregnant than non-pregnant group during days 12.5-17.5. Water intake patterns corresponded to food intake. From days 0.5-6.5 onwards, the pregnant group moved less during the dark phase, with decreased probability of being awake, in comparison to the non-pregnant group. The onset of dark-phase activity, peaks in activity, and wakefulness were all delayed during pregnancy. In conclusion, increased food intake during pregnancy reflects increased amplitude of eating behaviour, without longer duration. Decreases in activity also contribute to positive energy balance in pregnancy, with delays to all measured behaviours evident from mid-pregnancy onwards. KEY POINTS: Circadian rhythms synchronise daily behaviours including eating, drinking and sleep, but how these change in pregnancy is unclear. Food intake increased, with delays in peaks of food intake behaviour late in the light phase from days 6.5 to 12.5 of pregnancy, in comparison to the non-pregnant group. The onset of activity after lights off (dark phase) was delayed in pregnant compared with non-pregnant mice. Activity decreased by ∼70% in the pregnant group, particularly in the dark (active) phase, with delays in peaks of wakefulness evident from days 0.5-6.5 of pregnancy onwards. These behavioural changes contribute to positive energy balance during pregnancy. Delays in circadian behaviours during mouse pregnancy were time period and pregnancy stage specific, implying different regulatory mechanisms.

Activation of amygdala prokineticin receptor 2 neurons drives the anorexigenic activity of the neuropeptide PK2.

Energy homeostasis is a complex system involving multiple hormones, neuropeptides, and receptors. Prokineticins (PK1 and PK2) are agonists to two G protein-coupled receptors, prokineticin receptor 1 and 2 (PKR1 and PKR2), which decrease food intake when injected in rodents. The relative contribution of PKR1 and PKR2 to the anorexigenic effect of PK2 and their site of action in the brain have not yet been elucidated. While PKR1 and PKR2 are both expressed in the hypothalamus, a central region involved in the control of energy homeostasis, PKR2 is also present in the amygdala, which has recently been shown to regulate food intake in response to several anorexigenic signals. PKR trafficking and signaling are inhibited by the melanocortin receptor accessory protein 2 (MRAP2), thus suggesting that MRAP2 has the potential to alter the anorexigenic activity of PK2 in vivo. In this study, we investigated the importance of PKR1 and PKR2 for PK2-mediated inhibition of food intake, the brain region involved in this function, and the effect of MRAP2 on PK2 action in vivo. Using targeted silencing of PKR2 and chemogenetic manipulation of PKR2 neurons, we show that the anorexigenic effect of PK2 is mediated by PKR2 in the amygdala and that altering MRAP2 expression in PKR2 neurons modulates the activity of PK2. Collectively, our results provide evidence that inhibition of food intake by PKs is not mediated through activation of hypothalamic neurons but rather amygdala PKR2 neurons and further establishes the importance of MRAP2 in the regulation of energy homeostasis.

Intensive Multidisciplinary Feeding Day Programs in the United States: A Report Regarding the Treatment Landscape.

Intensive multidisciplinary intervention is increasingly recognized as the standard of care for children with complex feeding problems. Much, however, remains unknown about this treatment model. This current qualitative, prospective study sought to identify intensive multidisciplinary day hospital programs operating in the US, describe the treatment approach, and summarize current capacity.

Variety of High and Very Low-Energy Density Foods among Preschool-Aged Children and Associations with Food Intake, Diet Quality, and Weight Status.

BACKGROUND: Energy density (ED) and the variety of foods are 2 factors that may have a combined effect on preschool-aged children's ability to regulate food intake. However, little is known about the variety of foods consumed within different ED categories by children in the United States. OBJECTIVE: Therefore, we explored the variety of high ED (HED, 4-9 kcal/g) and very low ED (VLED, <0.6 kcal/g) foods consumed by a nationally representative sample of children aged 2-5 y in the United States and the relationship between variety with food intake, diet quality, and weight status. METHODS: ED, variety, and diet quality were assessed using two 24-h dietary recalls collected as part of the National Health And Nutrition Examination Survey 2011-2018 cycles (n = 1682). We assessed associations between HED and VLED varieties with energy intake, volume of food, diet quality, and weight status using multivariable linear and logistic regressions. RESULTS: The HED variety was positively associated with energy intake (P < 0.0001). The VLED variety was positively associated with the volume of food (P < 0.0001) and diet quality (P < 0.0001). VLED was negatively associated with the odds of having obesity in minimally adjusted models [odds ratio (OR): 0.62; 95% confidence interval (CI): 0.31, 0.87]; however, the relationship was not significant in fully adjusted models. Patterns of variety intake were differently associated with energy, volume, and diet quality. Children consuming the high VLED variety and the low HED variety had lower odds of obesity [OR: 0.43; 95% CI: 0.21, 0.90]; however, this pattern was rare (10%). CONCLUSIONS: These findings suggest that the variety of HED foods is associated with higher average energy intake per day, and the variety of VLED foods is associated with a higher volume of food consumed per day and diet quality in a nationally representative sample of preschool-aged children.

Mice Regulate Dietary Amino Acid Balance and Energy Intake by Selecting between Complementary Protein Sources.

BACKGROUND: A balanced intake of protein and constituent amino acids (AAs) requires adjustments to total food intake (protein leverage [PL]) and food selection to balance deficits and excesses (complementary feeding). We provided mice with choices of casein and whey, 2 protein sources that are complementary in AA balance, across a range of protein concentrations (P%) of digestible energy (DE). OBJECTIVES: We aimed to determine if: 1) PL operates similarly for casein and whey; 2) one protein source is preferred at control P%; 3) the preference changes as P% falls; and 4) AA intakes under control and low P% levels identify AAs that drive changes in protein selection. METHODS: Food intake and plasma fibroblast growth factor-21 (FGF21) concentrations were measured in mice at various P% (P7.5%-P33%). For direct comparisons, defined diets were used in which the protein source was either casein or whey. In food choice studies, mice had access to foods in which both casein and whey were provided at the same P% level at the same time. RESULTS: PL operated at different P% thresholds in casein (13%)- and whey (10%)-based diets, and the magnitude of PL was greater for casein. Although mice preferred casein under control conditions (P23%), a pronounced preference shift to whey occurred as P% fell to P13% and P10%. At low P%, increases in food intake were accompanied by increases in plasma FGF21, a protein hunger signal. Among AAs deficient in casein and enriched in whey, the intake of Cys was the most invariant as P% changed between P23% and P10%, appearing to drive the switch in protein preference. CONCLUSIONS: Mice selected between complementary protein sources, casein and whey, achieving stable total energy intake and regulated intake of AAs as P% varied. Supplementation of low P% casein diets with one whey-enriched AA, Cys, suppressed plasma FGF21 and total food intake.

Interactions of Body Weight Loss with Lipophilic Toxin Storage: Commentary.

A high incidence of obesity and surplus body fat has been observed in wealthy countries for many decades. It is generally recognized that these excesses contribute to serious disease states, including type 2 diabetes and cardiovascular diseases. On the other hand, the adipose tissue stores relatively safely many environmental lipophilic toxins. However, rapid weight loss mobilizes these toxins to the blood to be exposed to vital organs, such as the brain, lungs, and others. With the introduction of potent diabetic drugs causing rapid weight reduction, the question of mobilization of lipophilic toxins to the blood should be considered. In this commentary, we raised this mobilization of adipose tissue toxins to the readers. Also, we discussed how these toxins may be eliminated from the body through the use of nondigestible fat, such as olestra or lipase inhibitors, such as Xenical.

Mendelian randomization analysis reveals fresh fruit intake as a protective factor for urolithiasis.

OBJECTIVE: Previous studies have proposed that food intakes are associated with the risk of urolithiasis. Here, we conducted a two-sample Mendelian randomization (MR) study to evaluate the causal effects of different food intakes on urolithiasis. METHODS: Independent genetic variants associated with different food intakes at a genome-wide significant level were selected from summary-level statistics of genome-wide association studies from the UK Biobank. The association of these instrumental variables with urolithiasis was studied in a cohort from FinnGen Consortium. RESULTS: Among the 15 studied food intake exposures, tea intake (odds ratio [OR] = 0.433, 95% confidence interval [CI] = 0.281-0.667, p value = 1.470 × 10-4) and fresh fruit intake (OR = 0.358, 95% CI = 0.185-0.694, p value = 0.002) were found to significantly reduce the risk of the calculus of kidney and ureter. The association remained consistent in the sensitivity analyses. After adjusting for the effects of vitamin D and vitamin C, fresh fruit intake remained the reverse causal association with the calculus of kidney and ureter. CONCLUSIONS: Genetically proxied fresh fruit intake is causally associated with a reduced risk of the calculus of kidney and ureter.

Latent profile analysis reveals overlapping ARFID and shape/weight motivations for restriction in eating disorders.

BACKGROUND: DSM-5 differentiates avoidant/restrictive food intake disorder (ARFID) from other eating disorders (EDs) by a lack of overvaluation of body weight/shape driving restrictive eating. However, clinical observations and research demonstrate ARFID and shape/weight motivations sometimes co-occur. To inform classification, we: (1) derived profiles underlying restriction motivation and examined their validity and (2) described diagnostic characterizations of individuals in each profile to explore whether findings support current diagnostic schemes. We expected, consistent with DSM-5, that profiles would comprise individuals endorsing solely ARFID or restraint (i.e. trying to eat less to control shape/weight) motivations. METHODS: We applied latent profile analysis to 202 treatment-seeking individuals (ages 10-79 years [M = 26, s.d. = 14], 76% female) with ARFID or a non-ARFID ED, using the Nine-Item ARFID Screen (Picky, Appetite, and Fear subscales) and the Eating Disorder Examination-Questionnaire Restraint subscale as indicators. RESULTS: A 5-profile solution emerged: Restraint/ARFID-Mixed (n = 24; 8% [n = 2] with ARFID diagnosis); ARFID-2 (with Picky/Appetite; n = 56; 82% ARFID); ARFID-3 (with Picky/Appetite/Fear; n = 40; 68% ARFID); Restraint (n = 45; 11% ARFID); and Non-Endorsers (n = 37; 2% ARFID). Two profiles comprised individuals endorsing solely ARFID motivations (ARFID-2, ARFID-3) and one comprising solely restraint motivations (Restraint), consistent with DSM-5. However, Restraint/ARFID-Mixed (92% non-ARFID ED diagnoses, comprising 18% of those with non-ARFID ED diagnoses in the full sample) endorsed ARFID and restraint motivations. CONCLUSIONS: The heterogeneous profiles identified suggest ARFID and restraint motivations for dietary restriction may overlap somewhat and that individuals with non-ARFID EDs can also endorse high ARFID symptoms. Future research should clarify diagnostic boundaries between ARFID and non-ARFID EDs.

Goal pursuit increases more after dietary success than after dietary failure: examining conflicting theories of self-regulation using ecological momentary assessment.

BACKGROUND: Maintaining a healthy body weight and reaching long-term dietary goals requires ongoing self-monitoring and behavioral adjustments. How individuals respond to successes and failures is described in models of self-regulation: while cybernetic models propose that failures lead to increased self-regulatory efforts and successes permit a reduction of such efforts, motivational models (e.g., social-cognitive theory) make opposite predictions. Here, we tested these conflicting models in an ecological momentary assessment (EMA) context and explored whether effort adjustments are related to inter-individual differences in perceived self-regulatory success in dieting (i.e., weight management). METHODS: Using linear mixed effects models, we tested in 174 diet-interested individuals whether current day dietary success or failure (e.g., on Monday) was followed by self-regulatory effort adjustment for the next day (e.g., on Tuesday) across 14 days. Success vs. failure was operationalized with two EMA items: first, whether food intake was higher vs. lower than usual and second, whether food intake was perceived as more vs. less goal-congruent than usual. Trait-level perceived self-regulatory success in dieting was measured on a questionnaire. RESULTS: Intended self-regulatory effort increased more strongly after days with dietary success (i.e., eating less than usual / rating intake as goal-congruent) than after days with dietary failure (i.e., eating more than usual / rating intake as goal-incongruent), especially in those individuals with lower scores on perceived self-regulatory success in dieting. CONCLUSIONS: Findings support mechanisms proposed by social-cognitive theory, especially in unsuccessful dieters. Thus, future dietary interventions could focus on preventing the decrease in self-regulatory effort after instances of dietary failures and thereby mitigate the potential risk that a single dietary failure initiates a downward spiral into unhealthy eating.

Eating time variation from weekdays to weekends and its association with dietary intake and BMI in different chronotypes: findings from National Health and Nutrition Examination Survey (NHANES) 2017-2018.

Evidence suggests that differences in meal timing between weekends and weekdays can disrupt the body's circadian rhythm, leading to a higher BMI. We aimed to investigate the associations between mealtime variation from weekdays to weekends (eating midpoint jetlag), dietary intake and anthropometric parameters, based on individuals' chronotype. The study utilised data from National Health and Nutrition Examination Survey 2017-2018. Food consumption was estimated by weighted average of participants' food intake on weekdays and weekends. Eating midpoint jetlag, defined as the difference between the midpoint of the first and last mealtimes on weekends and weekdays, was calculated. Chronotype was assessed by participants' mid-sleep time on weekends, adjusted for sleep debt. Linear regression analysis was conducted to investigate the associations between variables. The sample was categorised into chronotype tertiles. Among individuals in the third chronotype tertile, there was a positive association between eating midpoint jetlag and BMI (ß = 1·2; 95 % CI (1·13, 1·27)). Individuals in the first tertile showed a positive association between eating midpoint jetlag and energy (ß = 96·9; 95 % CI (92·9, 101·7)), carbohydrate (ß = 11·96; 95 % CI (11·2, 12·6)), fat (ß = 3·69; 95 % CI (3·4, 3·8)), cholesterol (ß = 32·75; 95 % CI (30·9, 34·6)) and sugar (ß = 8·84; 95 % CI (8·3, 9·3)) intake on weekends. Among individuals with an evening tendency, delaying meals on weekends appears to be linked to a higher BMI. Conversely, among individuals with a morning tendency, eating meals later on weekends is associated with higher energetic intake on weekends.

24-h passive heat and cold exposures did not modify energy intake and appetite but strongly modify food reward.

Effects of acute thermal exposures on appetite appear hypothetical in reason of very heterogeneous methodologies. The aim of this study was therefore to clearly define the effects of passive 24-h cold (16°C) and heat (32°C) exposures on appetitive responses compared to a thermo neutral condition (24°C). Twenty-three healthy, young, and active male participants realised three sessions (from 1 pm) in a laboratory conceived like an apartment dressed with the same outfit (Clo=1). Three meals composed of three or four cold or warm dishes were served ad libitum to assess energy intake (EI). Leeds Food Preference Questionnaires were used before each meal to assess food reward. Subjective appetite was regularly assessed and levels of appetitive hormones (acylated ghrelin, GLP-1, leptin, and PYY) were assessed before and after the last meal (lunch). Contrary to the literature, total EI was not modified by cold or heat exposure (p=0.120). Accordingly, hunger scores (p=0.554) were not altered. Levels of acylated ghrelin and leptin were marginally higher during the 16 (p=0.032) and 32°C (p<0.023) sessions, respectively. Interestingly, implicit wanting for cold and low-fat foods at 32°C and for warm and high-fat foods at 16°C were increased during the whole exposure (p < 0.024). Moreover, cold entrées were more consumed at 32 °C (p<0.062) and warm main dishes more consumed at 16°C (p<0.025). Thus, passive cold and hot exposures had limited effects on appetite and it seems that offering some choice based on food temperature may help individuals to express their specific food preferences and maintain EI.

Association between sleep duration and quality with food intake, chrononutrition patterns, and weight gain during pregnancy.

To analyse the association between sleep duration and quality with food intake, chrononutrition patterns, and weight gain during pregnancy. A prospective cohort study was conducted with 100 pregnant women. Data collection occurred once during each gestational trimester. The assessment of sleep quality and duration was performed using the Pittsburgh Sleep Quality Index. Food intake was assessed using three 24-h recalls in each trimester. Body weight was measured during the three trimesters, and height was measured only once to calculate the BMI. Linear regression analyses were performed to associate sleep duration and quality with food consumption and weight gain variables. Longer sleep duration was associated with a later dinner in the first trimester (ß = 0·228, P = 0·025) and earlier in the third trimester (ß = -0·223, P = 0·026), in addition to a later morning snack in the second trimester (ß = 0·315, P = 0·026). Worse sleep quality was associated with higher total energy intake (ß = 0·243, P = 0·044), total fat (ß = 0·291, P = 0·015) and the chrononutrition variables such as a higher number of meals (ß = 0·252, P = 0·037), higher energetic midpoint (ß = 0·243, P = 0·044) and shorter fasting time (ß = -0·255, P = 0·034) in the third trimester. Sleep quality was also associated with a higher BMI in the first trimester of pregnancy (ß = 0·420, P = < 0·001). Most of the associations found in the present study show that poor sleep is associated with higher energy and fat intake and higher BMI. Longer sleep duration was associated with a later dinner in early pregnancy and an earlier dinner in late pregnancy, as well as with a later morning snack in the second trimester of pregnancy.

Role of melanocortin system in the locomotor activity rhythms and melatonin secretion as revealed by agouti-signalling protein (asip1) overexpression in zebrafish.

Temporal signals such as light and temperature cycles profoundly modulate animal physiology and behaviour. Via endogenous timing mechanisms which are regulated by these signals, organisms can anticipate cyclic environmental changes and thereby enhance their fitness. The pineal gland in fish, through the secretion of melatonin, appears to play a critical role in the circadian system, most likely acting as an element of the circadian clock system. An important output of this circadian clock is the locomotor activity circadian rhythm which is adapted to the photoperiod and thus determines whether animals are diurnal or nocturnal. By using a genetically modified zebrafish strain known as Tg (Xla.Eef1a1:Cau.asip1)iim04, which expresses a higher level of the agouti signalling protein 1 (Asip1), an endogenous antagonist of the melanocortin system, we observed a complete disruption of locomotor activity patterns, which correlates with the ablation of the melatonin daily rhythm. Consistent with this, in vitro experiments also demonstrated that Asip1 inhibits melatonin secretion from the zebrafish pineal gland, most likely through the melanocortin receptors expressed in this gland. Asip1 overexpression also disrupted the expression of core clock genes, including per1a and clock1a, thus blunting circadian oscillation. Collectively, these results implicate the melanocortin system as playing an important role in modulating pineal physiology and, therefore, circadian organisation in zebrafish.

Apparent digestibility and nutritional status of capuchin monkeys (Sapajus sp.) under human care.

BACKGROUND: Studing the nutritional needs and dietary habits of primates is essential to ensure their health and well-being. This includes the understanding of the use of nutrients and its correlation with health parameters. METHODS: Diet and nutritional parameters of 13 captive capuchin monkeys (Sapajus sp.) were assesed. Apparent digestibility of dry matter and nutrients were evaluated. Nutritional status was established based on body condition score (BCS) and muscle mass score (MMS). RESULTS: High apparent digestibility coefficients (ADC) were observed for crude protein and ether extract, but low for minerals and crude fiber. The ADC of EE and CF were related to MMS, and the biochemical parameters did not correlate with the AD coefficients obtained in the group. The nutritional status of the animals remained inadequate in 84.6% of the individuals, suggesting a reformulation of the diet and nutritional management.

Types of fish consumption differ across socioeconomic strata and impact differently on plasma fish-based omega-3 fatty acids: a cross-sectional study.

PURPOSE: We investigated the associations of socioeconomic position (SEP) with total and type of fish intake in a large general population and validated whether types of fish intake were differently associated with plasma EPA and DHA in a subset of the population. METHODS: From the Lifelines Cohort Study, 94,246 participants aged 44 ± 13 years old were included to test the association of two SEP indicators, i.e., education level and household income level, with dietary intakes of total, oily, lean, fried, and other types of fish. In a subset of 575 participants (mean age: 50 ± 13 years), EPA and DHA levels were measured in plasma phospholipids and triglycerides. Dietary fish intake was assessed using Food Frequency Questionnaire. Linear regressions were applied and adjusted for relevant covariates. RESULTS: Compared to the high education level, lower education levels were negatively associated with total, oily, lean, and other fish intake (p < 0.001 for all), and positively associated with fried fish intake (ß (SE): 0.04 (0.04), p < 0.001 for middle education; 0.07 (0.04), p < 0.001 for low education), independently of relevant covariates. Similar results were observed for income levels. In the subset population, total and oily fish intakes were positively associated with plasma EPA and DHA (p < 0.02 for all). Lean and other fish intakes were positively associated with only DHA (p < 0.008 for all), but not EPA, while fried fish was not associated with either EPA or DHA in plasma (p > 0.1 for all). CONCLUSION: Lower SEP was associated with a lower total intake of fish, and of oily and lean fish, but with higher intake of fried fish. Fried fish was not associated with the fish-based EPA and DHA in plasma. Hence, SEP-related differences in fish consumption are both quantitative and qualitative.

The role of food during oncology treatment: perspectives of cancer patients, caregivers and healthcare professionals.

PURPOSE: Many cancer patients have problems eating which are usually connected to taste and smell alterations due to side effects of cancer treatment. These problems have consequences both in terms of malnutrition and reduced quality of life. In order to explore social and psychological consequences of eating problems in cancer patients, qualitative interviews were conducted with cancer patients, their caregivers and healthcare professionals. METHODS: The study was conducted in three European countries (Poland, Spain and the UK) that differed in culture, oncology care approaches and availability of nutritional products targeted to cancer patients in the market. RESULTS: Differences in the social role of eating between the three European countries were observed which subsequently influenced the impact of eating problems for cancer patients in these countries. Furthermore, the study found that problems with food affect not only the quality of life of cancer patients, but can also distress their caregivers, who are often unable to cope with such food-related problems. In addition, the study showed that commercially available nutritional products for cancer patients focus on nutritional value but tend to neglect an important aspect of eating, which is the enjoyment of food, both individually and socially.