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BACKGROUND: Cardiovascular (CV) pathologies remain a leading cause of death worldwide, often associated with common comorbidities such as overweight, obesity, type 2 diabetes or hypertension. An innovative mouse model of metabolic syndrome induced by postnatal overfeeding (PNOF) through litter size reduction after birth was developed experimentally. This study aimed to evaluate the impact of PNOF on cardiac remodelling and the development of heart failure following myocardial infarction. METHODS: C57BL/6 male mice were raised in litter adjusted to 9 or 3 pups for normally-fed (NF) control and PNOF group respectively. After weaning, all mice had free access to standard diet and water. At 4 months, mice were subjected to myocardial infarction (MI). Echocardiographic follows-up were performed up to 6-months post-surgery and biomolecular analyses were carried-out after heart collection. FINDINGS: At 4 months, PNOF mice exhibited a significant increase in body weight, along with a basal reduction in left ventricular ejection fraction (LVEF) and an increase in left ventricular end-systolic area (LVESA), compared to NF mice. Following MI, PNOF mice demonstrated a significant decrease in stroke volume and an increased heart rate compared to their respective initial values, as well as a notable reduction in cardiac output 4-months after MI. After 6-months, left ventricle and lung masses, fibrosis staining, and mRNA expression were all similar in the NF-MI and PNOF-MI groups. INTERPRETATION: After MI, PNOF mice display signs of cardiac function worsening as evidenced by a decrease in cardiac output, which could indicate an early sign of heart failure decompensation.

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Obesity-related co-morbidities decrease life quality, reduce working ability, and lead to early death. In the adult population, eating addiction manifests with excessive food consumption and the unrestrained overeating behavior, which is associated with increased risk of morbidity and mortality and defined as the binge eating disorder (BED). This hedonic intake is correlated with fat preference and the total amount of dietary fat consumption is the most potent risk factor for weight gain. Long-term BED leads to greater sensitivity to the rewarding effects of palatable foods and results in obesity fatefully. Increased plasma concentrations of non-esterified free fatty acids and lipid-overloaded hypertrophic adipocytes may cause insulin resistance. In addition to dietary intake of high-fat diet, sedentary lifestyle leads to increased storage of triglycerides not only in adipose tissue but also ectopically in other tissues. Lipid-induced apoptosis, ceramide accumulation, reactive oxygen species overproduction, endoplasmic reticulum stress, and mitochondrial dysfunction play role in the pathogenesis of lipotoxicity. Food addiction and BED originate from complex action of dopaminergic, opioid, and cannabinoid systems. BED may also be associated with both obesity and major depressive disorder. For preventing morbidity and mortality, as well as decreasing the impact of obesity-related comorbidities in appropriately selected patients, opiate receptor antagonists and antidepressant combination are recommended. Pharmacotherapy alongside behavioral management improves quality of life and reduces the obesity risk; however, the number of licensed drugs is very few. Thus, stereotactic treatment is recommended to break down the refractory obesity and binge eating in obese patient. As recent applications in the field of non-invasive neuromodulation, transcranial magnetic stimulation and transcranial direct current stimulation are thought to be important in image-guided deep brain stimulation in humans. Chronic overnutrition most likely provides repetitive and persistent signals that up-regulate inhibitor of nuclear factor kappa B (NF-κB) kinase beta subunit/NF-κB (IKKß/NF-κB) in the hypothalamus before the onset of obesity. However, how the mechanisms of high-fat diet-induced peripheral signals affect the hypothalamic arcuate nucleus remain largely unknown.

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Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is closely associated with chronic low-grade inflammation and insulin resistance. To clarify the contribution of prepubertal weight gain to the development of insulin resistance in PCOS, we investigated the effects of early postnatal overfeeding on inflammatory and energy-sensing pathways as well as on markers of insulin signaling in the liver of the PCOS rat model. Methods: Obesity induced by overfeeding was achieved by reducing litter size, while the PCOS-like condition was developed by treatment with 5α-dihydrotestosterone (DHT). Western blot and qPCR were used to analyze the expression of pro-inflammatory transcription factors and cytokines, as well as markers of the energy sensing and insulin signaling pathways. Results: The results showed that hepatic insulin sensitivity was impaired only in DHT-treated rats raised in small litters, as evidenced by increased phosphorylation of IRS1 on Ser307 and decreased expression of total IRS1. Postnatal overfeeding stimulated JNK1 activation independent of hyperandrogenemia; nevertheless, the synergistic effect of both factors triggered NLRP3 activation and increased IL1ß expression in the small litter DHT-treated group. This pro-inflammatory state was accompanied by decreased activatory phosphorylation of AMPK and reduced levels of its protein targets. Conclusions: Overfeeding in the early postnatal period leads to a decrease in hepatic insulin sensitivity in the rat model of PCOS, which is associated with decreased activation of AMPK and stimulation of the hepatic NLRP3-IL1ß signaling pathway. Accordingly, the inhibition of NLRP3 activation could provide a basis for the development of new therapeutic strategies for the treatment of insulin resistance in women with PCOS.

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Evidence is growing that the individual adjustment of energy targets guided by indirect calorimetry (IC) can improve outcome. With the development of a new generation of devices that are easier to use and rapid, it appears important to share knowledge and expertise that may be used to individualize nutrition care. Despite the focus of this tutorial being on one contemporary device, the principles of IC apply across existing devices and can assist tailoring the nutrition prescription and in assessing response to nutrition therapy. The present tutorial addresses its clinical application in intubated mechanically ventilated and spontaneously breathing adult patients (canopy), i.e. it covers the range from critical illness to outpatients. The cases that are presented show how the measured energy expenditure (mEE), and the respiratory quotient (RQ), i.e. the ratio of expired CO2 to consumed O2, should be applied in different cases, to adapt and individualize nutrition prescription, as it is a good marker of over- or underfeeding at the different stages of disease. The RQ also informs about the patient's body's capacity to use different substrates: the variations of RQ indicating the metabolic changes revealing insufficient or excessive feeding. The different cases reflect the use of a new generation device as a metabolic monitor that should be combined with other clinical observations and laboratory biomarkers. The tutorial also points to some shortcomings of the method, proposing alternatives.

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Introduction: Formula feeding is the only viable nutrition alternative for infants 0-6mos who cannot breastfeed. Among the drawbacks of formula feeding, however, is potential dilution or concentration errors in the formula during preparation that may lead to infant health issues. The present study aimed to investigate the accuracy of caregiver measurements as they prepared infant formula under multiple conditions, compared with manufacturer specifications. Methods: A diverse sample of caregivers (N = 84) participated in this cross-over experimental study. Participants hand-scooped infant formula powder and poured water to prepare 4oz. and 7oz. feedings, using both a standardized set of infant formula products and participants' own products. Linear mixed effects models were used to estimate fixed effects of target amount (4oz. versus 7oz) and products (participant versus researcher) on mean absolute percent error (MAPE) of measurement. Results: Across all conditions MAPE was significantly greater for measuring powder than for water (9.0% vs. 4.4%; p < 0.001) with a combined powder and water MAPE at 13.0%. Greater measurement error was associated with the odd-sized 7oz. preparation and participants' own products. Discussion: We observed considerable variability and substantial error during infant formula preparation, particularly for hand-scooping of powder, which tended toward higher values than the theoretical gold standard.

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Most trace minerals (TM) are fed above dairy cow requirements in commercial herds but their fate and effects on dairy cows have not been well documented. In this study, we evaluated the effects of feeding short-term sulfate TM above recommendations on apparent total-tract digestibility of nutrients, rumen fermentation characteristics, serum concentrations, milk yield and composition as well as milk, fecal, and urinary TM excretion in mid-lactation dairy cows. Eight multiparous Holstein cows [average body weight: 684 (SD: 29) kg at 82 (SD: 10) days in milk] in a quadruple 2 × 2 crossover design were fed a basal diet, differing in sulfate TM supplement concentrations, to provide either 0.11, 17, and 63 (control; CON) or 0.95, 114, and 123 (high trace minerals; HTM) mg of dietary Co, Mn, and Zn/kg of dry matter, respectively. Each experimental period had a 21-d adaptation to the diet, followed by a 10-d sample collection period. Feed ingredients and total feces and urine were collected during 4 consecutive d and rumen fluid was collected 0, 1, 2, 4, and 6 h relative to feeding. Milk yield was recorded daily and milk samples were collected on 4 consecutive milkings. Ingestion of Co, Mn, and Zn was higher for HTM compared with CON group by 216, 233, and 93%, respectively. Dry matter intake averaged 25.0 (SE = 0.6) kg/d, and apparent total-tract digestibility of major nutrients was similar between treatments. There was no measurable effect of HTM on ruminal pH, major volatile fatty acids, and protozoa counts. Isovalerate molar proportion was 9.4% greater for HTM compared with CON group. Neither milk yield (43.5 kg/d; SE = 0.8) nor milk fat and protein concentrations differed between treatments. Milk urea nitrogen concentration was significantly higher for HTM (11.7 mg/dL) compared with CON group (9.7 mg/dL; SE = 0.7). Fecal excretion of Co, Mn, and Zn increased by 223, 198, and 75%, respectively, for HTM compared with CON group. Urinary excretions of TM were marginal compared with feces, and only urinary Co and Mn were significantly higher for HTM than CON cows as similarly obtained for serum Co and Mn concentrations. Milk TM yields were not modified by treatments. In summary, short-term dietary sulfate TM supply over the recommendation did not improve cow performance but significantly increased fecal TM excretion, which could have impacts on TM accumulation in soils where manure is applied and could potentially result in leaching into nearby watersheds. Further studies are needed to evaluate the impact of high fecal TM excretion on the environment using the One Health approach. Moreover, the impacts of TM oversupply on milk production and cow health should be evaluated by long-term experiments.

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Postnatal overfeeding can increase the long-term risk of metabolic disorders, such as obesity, but the underlying mechanisms remain unclear and treatment approaches are limited. Receptor-interacting protein kinase 3 (RIPK3) is associated with several metabolic diseases. We investigated the effects of RIPK3 on neonatal overfeeding-related metabolic disorders. On postnatal day 3, litter sizes were adjusted to 9-10 (normal litters, NL) or 2-3 (small litters, SL) mice per dam to mimic postnatal overfeeding. After weaning, NL and SL mouse were fed normal diet. We generated an adeno-associated virus (AAV) carrying short hairpin RNA (shRNA) against Ripk3 and an empty vector as a control. The NL and SL groups were treated intravenously with 1×1012 vector genome of AAV vectors at week 6. The SL group showed a higher body weight than the NL group from week 3 of age through adulthood. At weeks 6 and 13, the SL group exhibited impaired glucose and insulin tolerance, RIPK3 up-regulation, and lipid accumulation in liver and adipose tissues. In the SL group, the genes involved in lipid synthesis and lipolysis were increased, whereas fatty acid ß-oxidation-related genes were weakened in adipose tissue and liver. At week 13, AAV-shRNA-Ripk3 ameliorated adipose tissue hypertrophy, hepatic steatosis, insulin resistance, and dysregulated lipid metabolism in the adipose tissue and liver of SL mice. These findings support a novel mechanism underlying the pathogenesis of postnatal overfeeding-related metabolic disorders and suggest potential therapeutic targets.

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Skeletal muscle microvascular blood flow (MBF) plays an important role in glucose disposal in muscle. Impairments in muscle MBF contribute to insulin resistance and prediabetes. Animal studies show that short-term (3 day) high-fat feeding blunts skeletal muscle MBF before impairing insulin-stimulated glucose disposal. It is not known whether this occurs in humans. We investigated the temporal impact of a 7-day high-calorie high-fat (HCHF) diet intervention (+52% kJ; 41% fat) on fasting and postprandial cardiometabolic outcomes in 14 healthy adults (18-37 yr). Metabolic health and vascular responses to a mixed-meal challenge (MMC) were measured at pre (day 0)-, mid (day 4)- and post (day 8)-intervention. There were no significant differences in body weight, body fat %, fasting blood glucose, and fasting plasma insulin concentrations at pre-, mid- and postintervention. Compared with preintervention there was a significant increase in insulin (but not glucose) total area under the curve in response to the MMC at midintervention (P = 0.041) and at postintervention (P = 0.028). Unlike at pre- and midintervention, at postintervention muscle MBF decreased at 60 min (P = 0.024) and 120 min (P = 0.023) after the MMC. However, macrovascular blood flow was significantly increased from 0 to 60 min (P < 0.001) and 120 min (P < 0.001) after the MMC at pre-, mid- and postintervention. Therefore, short-term HCHF feeding in healthy individuals leads to elevated postprandial insulin but not glucose levels and a blunting of meal-induced skeletal muscle MBF responses but not macrovascular blood flow responses.NEW & NOTEWORTHY This is the first study to investigate skeletal muscle microvascular blood flow (MBF) responses in humans after short-term high-calorie high-fat (HCHF) diet. The main findings were that HCHF diet causes elevated postprandial insulin in healthy individuals within 3 days and blunts meal-induced muscle MBF within 7 days, despite no impairments in postprandial glucose or macrovascular blood flow.

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Nutritional support is a critical component of care for critically ill patients, impacting their recovery and overall prognosis. Traditional approaches to feeding in the intensive care unit (ICU) have focused on meeting estimated energy requirements, often resulting in unintended consequences such as overfeeding and associated complications. Permissive underfeeding, a concept gaining attention recently, offers a more controlled approach by intentionally providing fewer calories than traditionally recommended. This comprehensive review explores the rationale, evidence, and practical considerations surrounding permissive underfeeding in critically ill patients. We discuss the physiological basis of permissive underfeeding, its potential benefits in mitigating the risks of overfeeding, and the challenges associated with implementation in clinical practice. Through an analysis of critical studies and clinical trials, we evaluate the comparative effectiveness of permissive underfeeding versus traditional feeding methods and examine its impact on patient outcomes. Recommendations for patient selection, monitoring, and future research directions are provided to guide clinicians in optimizing nutritional support strategies for critically ill individuals. By considering the role of permissive underfeeding alongside traditional feeding approaches, healthcare professionals can tailor nutritional interventions to individual patient needs, ultimately improving outcomes in the ICU.

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BACKGROUND: Fatty acids may influence lean tissue volume and skeletal muscle function. We previously reported in young lean participants that overfeeding PUFA compared with SFA induced greater lean tissue accumulation despite similar weight gain. OBJECTIVES: In a double-blind randomized controlled trial, we aimed to investigate if the differential effects of overfeeding SFA and PUFA on lean tissue accumulation could be replicated in individuals with overweight and identify potential determinants. Further, using substitution models, we investigated associations between SFA and PUFA concentrations with lean tissue volume in a large population-based sample (UK Biobank). METHODS: Sixty-one males and females with overweight [BMI (kg/m2): 27.3 (interquartile range (IQR), 25.4-29.3); age: 43 (IQR, 36-48)] were overfed SFA (palm oil) or n-6 (ω-6) PUFA (sunflower oil) for 8 wk. Lean tissue was assessed by MRI. We had access to n = 13,849 participants with data on diet, covariates, and MRI measurements of lean tissue, as well as 9119 participants with data on circulating fatty acids in the UK Biobank. RESULTS: Body weight gain mean (SD) was similar in PUFA (2.01 ± 1.90 kg) and SFA (2.31 ± 1.38 kg) groups. Lean tissue increased to a similar extent [0.54 ± 0.93 L and 0.67 ± 1.21 L for PUFA and SFA groups, respectively, with a difference between groups of 0.07 (-0.21, 0.35)]. We observed no differential effects on circulating amino acids, myostatin, or IL-15 and no clear determinants of lean tissue accumulation. Similar nonsignificant results for SFA and PUFA were observed in UK Biobank, but circulating fatty acids demonstrated ambiguous and sex-dependent associations. CONCLUSIONS: Overfeeding SFA or PUFA does not differentially affect lean tissue accumulation during 8 wk in individuals with overweight. A lack of dietary fat type-specific effects on lean tissue is supported by specified substitution models in a large population-based cohort consuming their habitual diet. This trial was registered at clinicaltrials.gov identifier as NCT02211612.

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Fatty acids are stored within the muscle as intramyocellular lipids (IMCL). Some, but not all, studies indicate that following a high-fat diet (HFD), IMCL may accumulate and affect insulin sensitivity. This systematic review and meta-analysis aimed to quantify the effects of an HFD on IMCL. It also explored the potential modifying effects of HFD fat content and duration, IMCL measurement technique, physical activity status, and the associations of IMCL with insulin sensitivity. Five databases were systematically searched for studies that examined the effect of ≥3 d of HFD (>35% daily energy intake from fat) on IMCL content in healthy individuals. Meta-regressions were used to investigate associations of the HFD total fat content, duration, physical activity status, IMCL measurement technique, and insulin sensitivity with IMCL responses. Changes in IMCL content and insulin sensitivity (assessed by hyperinsulinemic-euglycemic clamp) are presented as standardized mean difference (SMD) using a random effects model with 95% confidence intervals (95% CIs). Nineteen studies were included in the systematic review and 16 in the meta-analysis. IMCL content increased following HFD (SMD = 0.63; 95% CI: 0.31, 0.94, P = 0.001). IMCL accumulation was not influenced by total fat content (P = 0.832) or duration (P = 0.844) of HFD, physical activity status (P = 0.192), or by the IMCL measurement technique (P > 0.05). Insulin sensitivity decreased following HFD (SMD = -0.34; 95% CI: -0.52, -0.16; P = 0.003), but this was not related to the increase in IMCL content following HFD (P = 0.233). Consumption of an HFD (>35% daily energy intake from fat) for ≥3 d significantly increases IMCL content in healthy individuals regardless of HFD total fat content and duration of physical activity status. All IMCL measurement techniques detected the increased IMCL content following HFD. The dissociation between changes in IMCL and insulin sensitivity suggests that other factors may drive HFD-induced impairments in insulin sensitivity in healthy individuals. This trial was registered at PROSPERO as CRD42021257984.

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BACKGROUND & AIMS: The quantity gap between daily and loaded carbohydrates may affects blood glucose response to carbohydrate intake; however, no study has investigated the difference in 24-h span. This study aimed to determine differences in the 24-h glucose levels and variability in response to single-day carbohydrate overfeeding based on daily carbohydrate intake in healthy Japanese men. METHODS: Twenty male college students completed a 3-day dietary record and were divided into two groups based on whether their daily carbohydrate intake exceeded the median intake (H-CHO) or not (L-CHO). Thereafter, the participants consumed a high-carbohydrate diet (carbohydrate 8.1 g/kg/d) for 1 day. The 24-h glucose levels and glucose variability (CONGA1) were measured using a continuous glucose monitoring system. RESULTS: The mean daily carbohydrate intakes in the L-CHO and H-CHO groups were 3.9 ± 0.5 and 5.8 ± 0.6 g/kg/d, respectively (p < 0.001). The peak 24-h glucose level was not differ between the L-CHO group and the H-CHO group (8.0 ± 0.8 vs. 8.0 ± 1.0; p = 0.886). The mean 24-h glucose level was higher in the L-CHO group than in the H-CHO group (6.0 ± 0.3 vs. 5.6 ± 0.3 mmol/L; p = 0.010). The CONGA1 was higher in the L-CHO group than in the H-CHO group (5.40 ± 0.41 vs. 4.95 ± 0.25; p = 0.008). CONCLUSIONS: Mean glucose level and glucose variability in response to carbohydrate overfeeding were high in the individuals with small daily carbohydrate intake. These findings suggest that the large quantity gap between daily and loaded carbohydrates cause worse glucose control during carbohydrate overfeeding.

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Introducción: El soporte nutricional en el paciente crítico es un desafío tanto en la estimación de requerimientos como en el cumplimiento de su prescripción. Objetivo: Evaluar las relaciones entre la prescripción, el requerimiento y el cumplimiento del soporte nutricional de energía y proteínas según la fase de la enfermedad en el paciente crítico. Pacientes y método: Estudio observacional, analítico, de datos obtenidos a través de reclutamiento prospectivo (2020-2021), pacientes de 0-18 años hospitalizados en la unidad de cuidados intensivos o intermedios pediátrica. Se obtuvieron datos demográficos, antropométricos y del estado agudo (FA)/no agudo (FNA) de la enfermedad. Se determinaron la prescripción (P) (indicación nutricional), el gasto energético basal (GEB) (fórmula de Schofield), el cumplimiento (C) de soporte nutricional, el requerimiento (R) proteico, creándose las siguientes relaciones: P/GEB, P/R, C/GEB, C/R, C/P. (AU)

Introduction: In critically ill patients, nutritional support is a challenge in terms of both estimating their requirements and ensuring adherence to the prescribed treatment. Objective: To assess the association between requirements, prescription and adherence to energy and protein supplementation based on the phase of disease in critically ill patients. Sample and methods: We conducted a prospective, observational and analytical study in patients aged 0-18years admitted to the paediatric intensive or intermediate care unit in 2020-2021. We collected data on demographic and anthropometric characteristics and the phase of disease (acute phase [AP] vs. non-acute phase [nAP]), in addition to prescribing (P) (indication of nutritional support), basal metabolic rate (BMR, Schofield equation), adherence to nutritional support (A) and protein requirements (R), and calculated the following ratios: P/BMR, P/R, A/BMR, A/R, and A/P. (AU)

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Nutritional disturbances during the early postnatal period can have long-lasting effects on neurodevelopment and may be related to behavioural changes at adulthood. While such neuronal connection disruption can contribute to social and behaviour alterations, the dysregulation of the neuroendocrine pathways involved in nutrient-sensing balance may also cause such impairments, although the underlying mechanisms are still unclear. We aimed to evaluate sex-specific neurodevelopmental and behavioural changes upon postnatal overfeeding and determine the potential underpinning mechanisms at the central nervous system level, with a focus on the interconnection between synaptic and neuroendocrine molecular alterations. At postnatal day 3 (PND3) litters were culled to three animals (small litter procedure). Neurodevelopmental tests were conducted at infancy, whereas behavioural tests to assess locomotion, anxiety, and memory were performed at adolescence, together with molecular analysis of the hippocampus, hypothalamus, and prefrontal cortex. At infancy, females presented impaired acquisition of an auditory response, eye opening, olfactory discrimination, and vestibular system development, suggesting that female offspring neurodevelopment/maturation was deeply affected. Male offspring presented a transitory delay in locomotor performance., while both offspring had lower upper limb strength. At adolescence, both sexes presented anxious-like behaviour without alterations in short-term memory retention. Both males and females presented lower NPY1R levels in a region-specific manner. Furthermore, both sexes presented synaptic changes in the hippocampus (lower GABAA in females and higher GABAA levels in males), while, in the prefrontal cortex, similar higher GABAA receptor levels were observed. At the hypothalamus, females presented synaptic changes, namely higher vGLUT1 and PSD95 levels. Thus, we demonstrate that postnatal overfeeding modulates offspring behaviour and dysregulates nutrient-sensing mechanisms such as NPY and GABA in a sex- and brain-region-specific manner.

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Nutritional status during critical windows in early development can challenge metabolic functions and physiological responses to immune stress in adulthood, such as the systemic inflammation induced by lipopolysaccharide (LPS). The aim of this study was to investigate the long-term effects of post-natal over- and undernutrition on the anorexigenic effect of LPS and its association with neuronal activation in the brainstem and hypothalamus of male rats. Animals were raised in litters of 3 (small - SL), 10 (normal - NL), or 16 (large - LL) pups per dam. On post-natal day 60, male rats were treated with LPS (500 µg/Kg) or vehicle for the evaluation of food intake and c-Fos expression in the area postrema (AP), nucleus of solitary tract (NTS), and paraventricular (PVN), arcuate (ARC), ventromedial (VMH), and dorsomedial (DMH) nuclei of the hypothalamus. SL, NL, and LL animals showed a decreased food consumption after LPS treatment. In under- and normonourished animals, peripheral LPS induced an increase in neuronal activation in the brainstem, PaV, PaMP, and ARC and a decrease in the number of c-Fos-ir neurons in the DMH. Overnourished rats showed a reduced hypophagic response, lower neuron activation in the NTS and PaMP, and no response in the DMH induced by LPS. These results indicate that early nutritional programming displays different responses to LPS, by means of neonatal overnutrition decreasing LPS-mediated anorexigenic effect and neuronal activation in the NTS and hypothalamic nuclei.

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Over the last decade, the zebrafish has emerged as an important model organism for behavioural studies and neurological disorders, as well as for the study of metabolic diseases. This makes zebrafish an alternative model for studying the effects of energy disruption and nutritional quality on a wide range of behavioural aspects. Here, we used the zebrafish model to study how obesity induced by overfeeding regulates emotional and cognitive processes. Two groups of fish (n = 24 per group) were fed at 2% (CTRL) and 8% (overfeeding-induced obesity, OIO) for 8 weeks and tested for anxiety-like behaviour using the novel tank diving test (NTDT). Fish were first tested using a short-term memory test (STM) and then trained for four days for a long-term memory test (LTM). At the end of the experiment, fish were euthanised for biometric sampling, total lipid content, and triglyceride analysis. In addition, brains (eight per treatment) were dissected for HPLC determination of monoamines. Overfeeding induced faster growth and obesity, as indicated by increased total lipid content. OIO had no effect on anxiety-like behaviour. Animals were then tested for cognitive function (learning and memory) using the aversive learning test in Zantiks AD units. Results show that both OIO and CTRL animals were able to associate the aversive stimulus with the conditioned stimulus (conditioned learning), but OIO impaired STM regardless of fish sex, revealing the effects of obesity on cognitive processes in zebrafish. Obese fish did not show a deficiency in monoaminergic transmission, as revealed by quantification of total brain levels of dopamine and serotonin and their metabolites. This provides a reliable protocol for assessing the effect of metabolic disease on cognitive and behavioural function, supporting zebrafish as a model for behavioural and cognitive neuroscience.

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INTRODUCTION: In critically ill patients, nutritional support is a challenge in terms of both estimating their requirements and ensuring adherence to the prescribed treatment. OBJECTIVE: To assess the association between requirements, prescription and adherence to energy and protein supplementation based on the phase of disease in critically ill patients. SAMPLE AND METHODS: We conducted a prospective, observational and analytical study in patients aged 0-18 years admitted to the paediatric intensive or intermediate care unit in 2020-2021. We collected data on demographic and anthropometric characteristics and the phase of disease (acute phase [AP] vs. non-acute phase [nAP]), in addition to prescribing (P) (indication of nutritional support), basal metabolic rate (BMR, Schofield equation), adherence to nutritional support (A) and protein requirements (R), and calculated the following ratios: P/BMR, P/R, A/BMR, A/R, and A/P. RESULTS: The sample included 131 participants with a median age of 16 (4.5) months, of who 128 (97.7%) had comorbidities and 13 (9.9%) were in the AP. Comparing the phases of disease (AP vs. nAP), the median values for energy supplementation were P/BMR, 0.5 (IQR, 0.1-1.4) vs. 1.3 (IQR, 0.9-1.8) (P = 0.0054); A/BMR, 0.4 (IQR, 0-0.6) vs. 1.2 (IQR, 0.8-1.7) (P = 0.0005); A/P, 0.7 (IQR, 0-0.9) vs. 1 (IQR, 0.8-1) (P = 0.002), and for protein were P/R, 0.7 (IQR, 0-1.1) vs. 1.2 (0.9-1.6) (P = 0.0009); A/R 0.3 (IQR, 0-0.6) vs. 1.1 (IQR, 0.8-1.5) (P = 0.0002); A/P 0.7 (IQR, 0-1) vs. 1(IQR, 0.8-1) (P = 0.002). We found AP/nAP ratios greater than 110% for energy in the P/BMR (4 patients [30.8%]/72 patients [61%]; P = 0.007), A/BMR (3 [23%]/63 [53.4%]; P = 0.009) and A/P (1 [7%]/3 [2.5%]; P = 0.007). As for protein, more than 1.5 g/kg/day was prescribed in 3 patients (23.1%) in the AP and 71 (60.1%) in the nAP. We found adherence to the prescribed intake in 2 (15.4%) patients in the AP and 66 (56%) in the nAP. We found a correlation coefficient of 0.6 between the energy P/R and the protein P/R. Prescribed support was discontinued in 7 patients (53.8%) in the AP and 31 (26.3%) in the nAP (P = 0.002). CONCLUSIONS: The proportion of adherence to prescribed nutritional support was high in patients in the nAP of the disease. Overfeeding was frequent, more so in the nAP. We identified difficulties in adhering to prescribed support, chief of which was the discontinuation of feeding.

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Body weight is under physiological regulation. When body fat mass decreases, a series of responses are triggered to promote weight regain by increasing food intake and decreasing energy expenditure. Analogous, in response to experimental overfeeding, excessive weight gain is counteracted by a reduction in food intake and possibly by an increase in energy expenditure. While low blood leptin and other hormones defend against weight loss, the signals that oppose overfeeding-induced fat mass expansion are still unknown. In this article, we discuss insights gained from overfeeding interventions in humans and intragastric overfeeding studies in rodents. We summarize the knowledge on the relative contributions of energy intake, energy expenditure and energy excretion to the physiological defence against overfeeding-induced weight gain. Furthermore, we explore literature supporting the existence of unidentified endocrine and non-endocrine pathways that defend against weight gain. Finally, we discuss the physiological drivers of constitutional thinness and suggest that overfeeding of individuals with constitutional thinness represents a gateway to understand the physiology of weight gain resistance in humans. Experimental overfeeding, combined with modern multi-omics techniques, has the potential to unveil the long-sought signalling pathways that protect against weight gain. Discovering these mechanisms could give rise to new treatments for obesity. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

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Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age, often associated with obesity and insulin resistance. Childhood obesity is an important predisposing factor for the development of PCOS later in life. Being particularly interested in the interplay between prepubertal obesity and hyperandrogenemia, we investigated the effects of early postnatal overfeeding, accomplished by reducing litter size during the period of suckling, on energy sensing and insulin signaling pathways in the gastrocnemius muscle of a rat model of PCOS-induced by 5α-dihydrotestosterone (DHT). The combination of overfeeding and DHT treatment caused hyperinsulinemia and decreased systemic insulin sensitivity. Early postnatal overfeeding induced defects at critical nodes of the insulin signaling pathway in skeletal muscle, which was associated with reduced glucose uptake in the presence of hyperandrogenemia. In this setting, under a combination of overfeeding and DHT treatment, skeletal muscle switched to mitochondrial ß-oxidation of fatty acids, resulting in oxidative stress and inflammation that stimulated AMP-activated protein kinase (AMPK) activity and its downstream targets involved in mitochondrial biogenesis and antioxidant protection. Overall, a combination of overfeeding and hyperandrogenemia resulted in a prooxidative and insulin-resistant state in skeletal muscle. This was accompanied by the activation of AMPK, which could represent a potential therapeutic target in insulin-resistant PCOS patients.

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Hemorrhage syndrome in adipose tissues in the crest of the neck (HSCN), specifically in hemorrhagic adipose tissues on the longitudinally sectioned surface of the neck fat at the dorsal nuchal ligament, is prevalent in heavy horse breeds. Herein, we aimed to establish an ultrasonographic method to successfully diagnose HSCN in heavy horse breeds and assess its efficacy. Horses with homogeneous echogenicity images were included in the control group, whereas those with linear high-echogenicity images were classified as having HSCN. Horses with confirmed linear high-echogenicity images exhibited pathological features and significantly higher percentages of adipose tissue with hemorrhage than those observed in horses with homogeneous echogenicity images (P<0.01). Our results suggest the effectiveness of ultrasonography in identifying and diagnosing HSCN.

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