RESUMEN

Rumen-protected choline (RPC) promotes benefits in milk production, immunity, and health in dairy cows by optimizing lipid metabolism during transition period management and early lactation. However, the RPC success in dairy cows depends on choline bioavailability, which is affected by the type of protection used in rumen-protected choline. Therefore, our objectives were to determine the effects of a novel RPC on dry matter intake (DMI), identify markers of metabolism and immunity, and evaluate lactation performance. Dry Holstein (n = 48) cows at 245 ± 3 d of gestation were blocked by parity and assigned to control or RPC treatment within each block. Cows enrolled in the RPC treatment received 15 g/d of CholiGEM (Kemin Industries, Cavriago RE, Italy) from 21 d prepartum and 30 g/d of CholiGEM from calving to 21 d postpartum. During the transition period, DMI was measured daily, and blood was sampled weekly for energy-related metabolites such as ß-hydroxybutyrate (BHB), glucose, and nonesterified fatty acids (NEFA), as well as immune function markers such as haptoglobin (Hp) and lipopolysaccharide-binding protein (LPB). Vaginal discharge samples were collected at the calving and 7 d postpartum and stored in microcentrifuge tubes at -80°C until 16S rRNA sequencing. The main responses of body condition score, body weight, DMI, milk yield, milk components, and immune function markers were analyzed using the GLIMMIX procedure of SAS with the effects of treatment, time, parity, and relevant covariates added to the models. The relative abundance of microbiome α-diversity was evaluated by 3 indexes (Chao1, Shannon, and Simpson) and ß-diversity by principal coordinate analysis and permutational multivariate ANOVA. We found no differences in DMI in the pre- and postpartum periods. Cows fed RPC increased the yields of energy- and 3.5% fat-corrected milk and fat yield in primiparous and multiparous cows, with an interaction between treatment and parity for these lactation variables. However, we found no differences in milk protein and lactose up to 150 DIM between treatments. Glucose, NEFA, and BHB had no differences between the treatments. However, RPC decreased BHB numerically (control = 1.07 ± 0.13 vs. RPC = 0.63 ± 0.13) in multiparous on the third week postpartum and tended to reduce the incidence of subclinical ketosis (12.7% vs. 4.2%). No effects for Hp and LPB were found in cows fed RPC. Chao1, Shannon, and Simpson indexes were lower at calving in the RPC treatment than in the Control. However, no differences were found 7 d later for Chao1, Shannon, and Simpson indexes. The vaginal discharge microbiome was altered in cows fed RPC at 7 d postpartum. Fusobacterium, a common pathogen associated with metritis, was reduced in cows fed RPC. Rumen-protected choline enhanced lactation performance and health and altered the vaginal discharge microbiome which is a potential proxy for uterine healthy in dairy cows. The current study's findings corroborate that RPC is a tool to support adaptation to lactation and shed light on opportunities for further research in reproductive health.

Asunto(s)

Enfermedades de los Bovinos , Excreción Vaginal , Embarazo , Femenino , Bovinos , Animales , Colina/farmacología , Colina/metabolismo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Ácidos Grasos no Esterificados , Rumen/metabolismo , ARN Ribosómico 16S/metabolismo , Periodo Posparto/metabolismo , Lactancia/fisiología , Glucosa/metabolismo , Excreción Vaginal/veterinaria , Enfermedades de los Bovinos/metabolismo

RESUMEN

Butyrylcholinesterase (BChE), an enzyme primarily found in the liver, plasma, and brain, has been recognized for its role in the hydrolysis of choline esters. Recent studies have shed light on its involvement in lipid metabolism, revealing its potential as a crucial player in maintaining lipid homeostasis. However, the interactions between external factors and BChE activity in lipid metabolic pathways remain a complex subject of study. This review summarizes the current knowledge regarding BChE activity and lipid metabolism and seeks to clarify the nature of this relationship as causal or consequential. Evidence supports the role of BChE in energy homeostasis disruption, such as obesity and related metabolic disorders, where it exhibits lipolytic activity and mediates fatty acid use and storage. The unexpected functions of BChE in lipoprotein synthesis and the impact of polymorphic variants of the BCHE gene suggest a central role in lipid metabolism; however, further investigation is needed to confirm and describe these functions, especially considering the metabolic context. Furthermore, exploring therapeutic interventions in lipid metabolism disorders contributes to elucidating their implications on BChE activity, but attention to the metabolic status and genotypes as possible factors in this interaction is needed. In summary, further research in this field holds promise for improving our understanding of the complex interplay between BChE and lipid metabolism, and its potential clinical applications. However, the available data corroborate the dual role of BChE activity, both as a critical responsive element to metabolic challenges and as a predisposition factor to metabolic diseases.

Asunto(s)

Butirilcolinesterasa , Enfermedades Metabólicas , Humanos , Butirilcolinesterasa/genética , Metabolismo de los Lípidos , Genotipo , Ácidos Grasos

RESUMEN

BACKGROUND AND AIMS: The gut microbiome is associated with obesity, mainly mediated by bacteria-produced short-chain fatty acids (SCFAs). It is unknown how SCFA concentrations are associated with the phenotypes metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese/overweight (MHO), and metabolically unhealthy obese/overweight (MUO). We compared plasma and fecal SCFA concentrations among adult women categorized according to the metabolic phenotypes mentioned above and examined associations between SCFA and adiposity and components of energy and glucose homeostasis. METHODS: This was a cross-sectional study involving 111 participants. Body composition was assessed by DEXA. Energy and glycemic homeostasis were assessed by the standard mixed-meal tolerance test coupled with indirect calorimetry. SCFAs were quantified by gas chromatography and mass spectrometry. RESULTS: Only plasma propionate was increased in the MHNW phenotype compared to the MHO and MUO phenotypes [p < 0.05]. Fecal propionate and butyrate concentrations and plasma propionate concentrations were inversely associated with total and visceral adiposity [p < 0.05]. Fecal and plasma SCFA concentrations were associated with reduced glucose, insulin and HbA1c levels, increased fasting and postprandial GLP-1 levels; and more preserved beta-cell function [p < 0.05]. Fecal and plasma SCFA concentrations were positively correlated with resting energy expenditure and lipid oxidation rate and inversely correlated with the oxidation rate of carbohydrates [p < 0.05]. CONCLUSION: These findings reinforce the concept that fecal and plasma SCFA concentrations are linked to specific components of energy and glucose homeostasis; and body adiposity. However, it was not possible to discriminate the different metabolic phenotypes of adiposity based on the determination of fecal SCFA concentrations.

Asunto(s)

Síndrome Metabólico , Nutricionistas , Femenino , Humanos , Sobrepeso/metabolismo , Adiposidad , Propionatos , Estudios Transversales , Obesidad/metabolismo , Ácidos Grasos Volátiles , Fenotipo , Homeostasis , Glucosa , Índice de Masa Corporal , Síndrome Metabólico/metabolismo

RESUMEN

Obesity is defined as abnormal and excessive fat accumulation, and it is a risk factor for developing metabolic and neurodegenerative diseases and cognitive deficits. Obesity is caused by an imbalance in energy homeostasis resulting from increased caloric intake associated with a sedentary lifestyle. However, the entire physiopathology linking obesity with neurodegeneration and cognitive decline has not yet been elucidated. During the progression of obesity, adipose tissue undergoes immune, metabolic, and functional changes that induce chronic low-grade inflammation. It has been proposed that inflammatory processes may participate in both the peripheral disorders and brain disorders associated with obesity, including the development of cognitive deficits. In addition, mitochondrial dysfunction is related to inflammation and oxidative stress, causing cellular oxidative damage. Preclinical and clinical studies of obesity and metabolic disorders have demonstrated mitochondrial brain dysfunction. Since neuronal cells have a high energy demand and mitochondria play an important role in maintaining a constant energy supply, impairments in mitochondrial activity lead to neuronal damage and dysfunction and, consequently, to neurotoxicity. In this review, we highlight the effect of obesity and high-fat diet consumption on brain neuroinflammation and mitochondrial changes as a link between metabolic dysfunction and cognitive decline.

RESUMEN

Many cytokines have been proposed to regulate reproduction due to their actions on hypothalamic kisspeptin cells, the main modulators of gonadotropin-releasing hormone (GnRH) neurons. Hormones such as leptin, prolactin and growth hormone are good examples of cytokines that lead to Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation, consequently exerting effects in kisspeptin neurons. Different studies have investigated how specific components of the JAK/STAT signaling pathway affect the functions of kisspeptin cells, but the role of the suppressor of cytokine signaling 3 (SOCS3) in mediating cytokine actions in kisspeptin cells remains unknown. Cre-Loxp technology was used in the present study to ablate Socs3 expression in kisspeptin cells (Kiss1/Socs3-KO). Then, male and female control and Kiss1/Socs3-KO mice were evaluated for sexual maturation, energy homeostasis features, and fertility. It was found that hypothalamic Kiss1 mRNA expression is significantly downregulated in Kiss1/Socs3-KO mice. Despite reduced hypothalamic Kiss1 mRNA content, these mice did not present any sexual maturation or fertility impairments. Additionally, body weight gain, leptin sensitivity and glucose homeostasis were similar to control mice. Interestingly, Kiss1/Socs3-KO mice were partially protected against lipopolysaccharide (LPS)-induced body weight loss. Our results suggest that Socs3 ablation in kisspeptin cells partially prevents the sickness behavior induced by LPS, suggesting that kisspeptin cells can modulate energy metabolism in mice in certain situations.

Asunto(s)

Kisspeptinas , Lipopolisacáridos , Animales , Peso Corporal/fisiología , Citocinas/metabolismo , Femenino , Kisspeptinas/genética , Kisspeptinas/metabolismo , Leptina/metabolismo , Lipopolisacáridos/farmacología , Masculino , Ratones , ARN Mensajero , Proteína 3 Supresora de la Señalización de Citocinas/genética , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Pérdida de Peso

RESUMEN

BACKGROUND: Feed efficiency (FE) related traits play a key role in the economy and sustainability of beef cattle production systems. The accurate knowledge of the physiologic background for FE-related traits can help the development of more efficient selection strategies for them. Hence, multi-trait weighted GWAS (MTwGWAS) and meta-analyze were used to find genomic regions associated with average daily gain (ADG), dry matter intake (DMI), feed conversion ratio (FCR), feed efficiency (FE), and residual feed intake (RFI). The FE-related traits and genomic information belong to two breeding programs that perform the FE test at different ages: post-weaning (1,024 animals IZ population) and post-yearling (918 animals for the QLT population). RESULTS: The meta-analyze MTwGWAS identified 14 genomic regions (-log10(p -value) > 5) regions mapped on BTA 1, 2, 3, 4, 7, 8, 11, 14, 15, 18, 21, and 29. These regions explained a large proportion of the total genetic variance for FE-related traits across-population ranging from 20% (FCR) to 36% (DMI) in the IZ population and from 22% (RFI) to 28% (ADG) in the QLT population. Relevant candidate genes within these regions (LIPE, LPL, IGF1R, IGF1, IGFBP5, IGF2, INS, INSR, LEPR, LEPROT, POMC, NPY, AGRP, TGFB1, GHSR, JAK1, LYN, MOS, PLAG1, CHCD7, LCAT, and PLA2G15) highlighted that the physiological mechanisms related to neuropeptides and the metabolic signals controlling the body's energy balance are responsible for leading to greater feed efficiency. Integrated meta-analysis results and functional pathway enrichment analysis highlighted the major effect of biological functions linked to energy, lipid metabolism, and hormone signaling that mediates the effects of peptide signals in the hypothalamus and whole-body energy homeostasis affecting the genetic control of FE-related traits in Nellore cattle. CONCLUSIONS: Genes and pathways associated with common signals for feed efficiency-related traits provide better knowledge about regions with biological relevance in physiological mechanisms associated with differences in energy metabolism and hypothalamus signaling. These pleiotropic regions would support the selection for feed efficiency-related traits, incorporating and pondering causal variations assigning prior weights in genomic selection approaches.

Asunto(s)

Ingestión de Alimentos , Estudio de Asociación del Genoma Completo , Alimentación Animal/análisis , Animales , Bovinos/genética , Ingestión de Alimentos/genética , Metabolismo Energético/genética , Genómica , Fenotipo

RESUMEN

The hypothalamus-pituitary-thyroid-axis (HPT) is one of the main neuroendocrine axes that control energy expenditure. The activity of hypophysiotropic thyrotropin releasing hormone (TRH) neurons is modulated by nutritional status, energy demands and stress, all of which are sex dependent. Sex dimorphism has been associated with sex steroids whose concentration vary along the life-span, but also to sex chromosomes that define not only sexual characteristics but the expression of relevant genes. In this review we describe sex differences in basal HPT axis activity and in its response to stress and to metabolic challenges in experimental animals at different stages of development, as well as some of the limited information available on humans. Literature review was accomplished by searching in Pubmed under the following words: "sex dimorphic" or "sex differences" or "female" or "women" and "thyrotropin" or "thyroid hormones" or "deiodinases" and "energy homeostasis" or "stress". The most representative articles were discussed, and to reduce the number of references, selected reviews were cited.

Asunto(s)

Metabolismo Energético/fisiología , Sistema Hipotálamo-Hipofisario/fisiología , Caracteres Sexuales , Estrés Fisiológico/fisiología , Glándula Tiroides/fisiología , Adaptación Fisiológica/fisiología , Animales , Femenino , Humanos , Masculino

RESUMEN

BACKGROUND: Exercise is often used to obtain a negative energy balance. However, its effects on body weight reduction are usually below expectations. One possible explanation is a reduction in spontaneous physical activity (SPA) after exercise since the increase in energy expenditure caused by the exercise session would be offset by the decrease in SPA and its associated energy cost. Thus, we evaluated the effects of a single bout of moderate exercise at individualized intensity on spontaneous physical activity. The impact of the single bout of exercise was determined in early adulthood and at the transition to middle age. METHODS: Male C57bl/6j (n = 10) mice were evaluated at 4 (4 M) and 9 (9 M) months of age. One week after a treadmill Maximal Exercise Capacity Test (MECT), mice performed a 30-min single bout of exercise at 50 % of the maximal speed reached at MECT. An infrared-based system was used to determine locomotor parameters (SPA and average speed of displacement, ASD) before (basal) and immediately after the single bout of exercise for 48 h (D1, 0-24 h; D2, 24-48 h). Food intake was measured simultaneously. Data were analyzed by GEE and statistical significance was set at p < 0.05. RESULTS: Basal SPA declined from 4 M to 9 M (p = 0.01), but maximal exercise capacity was similar. At both ages, SPA and ASD decreased significantly (p < 0.0001) on day 1 after exercise. On D2, SPA returned to basal levels but ASD remained lower than basal (p < 0.001). The magnitude (% of basal) of change in SPA and ASD on D1 and D2 was similar at 4 M and 9 M. Food intake did not change at 4 M but decreased on D2 at 9 M. CONCLUSIONS: A single bout of moderate exercise decreases physical activity in the first 24 h and average speed of locomotion in the 48 h following exercise. This compensation is similar from early adulthood to the transition to middle age. The decrease in both the amount and intensity (speed) of SPA may compensate for the increase in energy expenditure induced by exercise, helping to understand the below-than-expected effect of exercise interventions to cause a negative energy balance.

RESUMEN

This work evaluated the effects of neonatal overfeeding, induced by litter size reduction, on fertility and the noradrenaline-kisspeptin-gonadotrophin releasing hormone (GnRH) pathway in adult female rats. The litter size was adjusted to 3 pups with each mother in the small litters (SL) and 10 pups with each mother in the normal litters (NL). SL females exhibited metabolic changes associated with reproductive dysfunctions, shown by earlier vaginal opening and first estrus, later regular cyclicity onset, and lower and higher occurrences of estrus and diestrus phases, respectively, as well as reduced fertility, estradiol plasma levels, and mRNA expressions of tyrosine hydroxylase in the locus coeruleus, kisspeptin, and GnRH in the preoptic area in adult females in the afternoon of proestrus. These results suggest that neonatal overfeeding in female rats promotes reproductive dysfunctions in adulthood, such as lower estradiol plasma levels associated with impairments in fertility and noradrenaline-kisspeptin-GnRH pathway during positive feedback.

Asunto(s)

Envejecimiento/fisiología , Estradiol/sangre , Fertilidad/fisiología , Hormona Liberadora de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Norepinefrina/metabolismo , Hipernutrición/sangre , Hipernutrición/metabolismo , Animales , Animales Recién Nacidos , Glucemia/metabolismo , Tronco Encefálico/patología , Ciclo Estral , Femenino , Hormona Liberadora de Gonadotropina/genética , Gónadas/patología , Hipotálamo/patología , Lípidos/sangre , Tamaño de la Camada , Masculino , Hipófisis/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Maduración Sexual , Aumento de Peso

RESUMEN

OBJECTIVES: The aim of this study was to examine whether paternal and maternal body mass indexes (BMIs) were independently associated with obestatin and visfatin levels in adult offspring. METHODS: This cross-sectional analysis included 124 women who participated in the Nutritionists' Health Study (NutriHS) at baseline. Early life events, anthropometry, dual-energy x-ray absorptiometry-determined body composition and blood sample were obtained. Associations of parental BMI with outcomes (obestatin and visfatin) were tested by multiple linear regression, using minimal sufficient adjustments recommended by Directed Acyclic Graph. Participants' mean BMI was 25 ± 5 kg/m2 and 74% were metabolically healthy. Median obestatin and visfatin levels were 56.4 pg/mL (42-72) and 17.7 ng/mL (14-21.8), respectively. Eleven percent of mothers and 39% of fathers were overweight/obese. RESULTS: Daughters born from overweight/obese mothers had higher BMI than those born from normal weight women (P = 0.003). In adjusted regression model, offspring obestatin levels were associated with maternal BMI (ß = -0.03; P = 0.045) and paternal BMI (ß = -0.02; P = 0.048) independently of maternal and paternal education, maternal age, and maternal use of tobacco, alcohol, and/or drugs. No association was detected with visfatin levels. CONCLUSION: Inverse associations of maternal and paternal BMIs with offspring obestatin concentrations in women could suggest a utility of this biomarker of energy regulation determined in early adulthood. Whether obestatin could be an indicator of protection against obesity-related disorders in the life course requires investigation in studies designed to test such hypothesis.

Asunto(s)

Padre , Adulto , Índice de Masa Corporal , Estudios Transversales , Femenino , Ghrelina , Humanos , Masculino , Madres , Obesidad

RESUMEN

Reproductive success requires that individuals acquire sufficient energy resources. Restricting food availability or increasing energy expenditure (e.g., thermoregulation) inhibits reproductive development in multiple avian species, but the nature of the energy-related signal mediating this effect is unclear. To investigate this question, we examined reproductive and metabolic physiology in male house finches that either underwent moderate food restriction (FR) or were exposed to high temperature (HT), in which birds were held at a high, but not locally atypical, ambient temperature cycle (37.8 °C day, 29.4 °C night) compared to a control group (CT; 29.4 °C day, 21.1 °C night). We hypothesized that FR and HT inhibit reproductive development by lowering available metabolic fuel, in particular plasma glucose (GLU) and free fatty acids (FFA). Following FR for 4 weeks, finches lost body mass, had marginally higher plasma FFA, and experienced a 90% reduction in testis mass compared to CT birds. Four weeks of HT exposure resulted in reduced voluntary food consumption and muscle mass, as well as an 80% reduction in testis mass relative to CT birds. Both FR and HT birds expressed less testicular 17ß-hydroxysteroid dehydrogenase (17ß-HSD) mRNA than controls but the expression of other testicular genes measured was unaffected by either treatment. Neither treatment significantly influenced plasma GLU. This study is among the first to demonstrate a negative effect of HT on reproductive development in a wild bird. Further studies are needed to clarify the role of metabolic mediators and their involvement under various conditions of energy availability and demand.

Asunto(s)

Ingestión de Alimentos , Metabolismo Energético , Pinzones/fisiología , Calor , Testículo/metabolismo , 17-Hidroxiesteroide Deshidrogenasas/genética , Animales , Proteínas Aviares/genética , Glucemia/análisis , Peso Corporal , Exposición a Riesgos Ambientales , Ácidos Grasos no Esterificados/metabolismo , Masculino , Músculo Esquelético/anatomía & histología , Testosterona/sangre

RESUMEN

3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency is a neurometabolic disorder characterized by predominant accumulation of 3-hydroxy-3-methylglutaric acid (HMG) in tissues and biological fluids. Patients often present in the first year of life with metabolic acidosis, non-ketotic hypoglycemia, hypotonia, lethargy, and coma. Since neurological symptoms may be triggered or worsened during episodes of metabolic decompensation, which are characterized by high urinary excretion of organic acids, this study investigated the effects of HMG intracerebroventricular administration on redox homeostasis, citric acid cycle enzyme activities, dynamics (mitochondrial fusion and fission), and endoplasmic reticulum (ER)-mitochondria crosstalk in the brain of neonatal rats euthanized 1 (short term) or 20 days (long term) after injection. HMG induced lipid peroxidation and decreased the activities of glutathione peroxidase (GPx) and citric acid cycle enzymes, suggesting bioenergetic and redox disruption, 1 day after administration. Levels of VDAC1, Grp75, and mitofusin-1, proteins involved in ER-mitochondria crosstalk and mitochondrial fusion, were increased by HMG. Furthermore, HMG diminished synaptophysin levels and tau phosphorylation, and increased active caspase-3 content, indicative of cell damage. Finally, HMG decreased GPx activity and synaptophysin levels, and changed MAPK phosphorylation 20 days after injection, suggesting that long-term toxicity is further induced by this organic acid. Taken together, these data show that HMG induces oxidative stress and disrupts bioenergetics, dynamics, ER-mitochondria communication, and signaling pathways in the brain of rats soon after birth. It may be presumed that these mechanisms underlie the onset and progression of symptoms during decompensation occurring in HL-deficient patients during the neonatal period.

Asunto(s)

Encéfalo/efectos de los fármacos , Retículo Endoplásmico/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Homeostasis/efectos de los fármacos , Meglutol/toxicidad , Dinámicas Mitocondriales/efectos de los fármacos , Animales , Encéfalo/metabolismo , Retículo Endoplásmico/metabolismo , Metabolismo Energético/fisiología , Femenino , Homeostasis/fisiología , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Dinámicas Mitocondriales/fisiología , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar

RESUMEN

BACKGROUND/AIMS: Cholinergic signalling mediated by the activation of muscarinic and nicotinic receptors has been described in the literature as a classic and important signalling pathway in the regulation of the inflammatory response. Recent research has investigated the role of acetylcholine, the physiological agonist of these receptors, in the control of energy homeostasis at the central level. Studies have shown that mice that do not express acetylcholine in brain regions regulating energy homeostasis present with excessive weight gain and hyperphagia. However, it has not yet been well-described in the literature which cholinergic receptor subunits are involved in this response; moreover, the signalling pathways responsible for the observed effects are not fully delineated. The hypothalamus is the regulating centre of energy homeostasis, and the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) is highly expressed in this region. When active, α7nAChR recruits proteins such as JAK2/STAT3 to mediate its signalling; the same intracellular components are required by leptin, an anorexigenic hormone. The aim of the present study was to evaluate the role of the hypothalamic α7nAChR in the control of energy homeostasis. METHODS: The work was performed on Swiss male mice. Initially, using immunofluorescent staining on brain sections, the presence of α7nAChR in hypothalamic cells regulating energy homeostasis was evaluated. Animals were submitted to stereotaxis in the lateral ventricle and intracerebroventricular stimulation (ICV) was used for the administration of an agonist (PNU) or antagonist (α-bungarotoxin) of α7nAChR. Metabolic parameters were evaluated and the expression of neuropeptides was evaluated in the hypothalamus by real-time PCR and western blot. The expression of hypothalamic neuropeptides was evaluated in mice treated with siRNA or inhibitors of JAK2/STAT3 (AG490 and STATTIC) proteins. We also evaluated food intake in α7nAChR knockout animals (α7KO). Additionally, in mouse hypothalamic cell culture (the mypHoA-POMC/GFP lineage), we evaluated the expression of neuropeptides and pSTAT3 after stimulation with PNU. RESULTS: Our results indicate co-localisation of α7nAChR with α-MSH, AgRP and NPY in hypothalamic cells. Pharmacological activation of α7nAChR reduced food intake and increased hypothalamic POMC expression and decreased NPY and AgRP mRNA levels and the protein content of pAMPK. Inhibition of α7nAChR with an antagonist increased the mRNA content of NPY and AgRP. Inhibition of α7nAChR with siRNA led to the suppression of POMC expression and an increase in AgRP mRNA levels. α7KO mice showed no changes in food intake. Inhibition of proteins involved in the JAK2/STAT3 signalling pathway reversed the effects observed after PNU stimulation. POMC-GFP cells, when treated with PNU, showed increased POMC expression and nuclear translocation of pSTAT3. CONCLUSION: Thus, selective activation of α7nAChR is able to modulate important markers of the response to food intake, suggesting that α7nAChR activation can suppress the expression of orexigenic markers and favour the expression of anorexics using the intracellular JAK2/STAT3 machinery.

Asunto(s)

Proteína Relacionada con Agouti/metabolismo , Janus Quinasa 2/metabolismo , Proopiomelanocortina/metabolismo , Factor de Transcripción STAT3/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Proteína Relacionada con Agouti/genética , Animales , Benzamidas/farmacología , Compuestos Bicíclicos con Puentes/farmacología , Bungarotoxinas/farmacología , Línea Celular , Ingestión de Alimentos/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 2/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/metabolismo , Proopiomelanocortina/genética , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/genética , Transducción de Señal/efectos de los fármacos , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Receptor Nicotínico de Acetilcolina alfa 7/antagonistas & inhibidores , Receptor Nicotínico de Acetilcolina alfa 7/genética

RESUMEN

The past 20 years have resulted in unprecedented progress in understanding brain energy metabolism and its role in health and disease. In this review, which was initiated at the 14th International Society for Neurochemistry Advanced School, we address the basic concepts of brain energy metabolism and approach the question of why the brain has high energy expenditure. Our review illustrates that the vertebrate brain has a high need for energy because of the high number of neurons and the need to maintain a delicate interplay between energy metabolism, neurotransmission, and plasticity. Disturbances to the energetic balance, to mitochondria quality control or to glia-neuron metabolic interaction may lead to brain circuit malfunction or even severe disorders of the CNS. We cover neuronal energy consumption in neural transmission and basic ('housekeeping') cellular processes. Additionally, we describe the most common (glucose) and alternative sources of energy namely glutamate, lactate, ketone bodies, and medium chain fatty acids. We discuss the multifaceted role of non-neuronal cells in the transport of energy substrates from circulation (pericytes and astrocytes) and in the supply (astrocytes and microglia) and usage of different energy fuels. Finally, we address pathological consequences of disrupted energy homeostasis in the CNS.

Asunto(s)

Encéfalo/metabolismo , Metabolismo Energético/fisiología , Neuroquímica/educación , Estudiantes , Animales , Astrocitos/metabolismo , Congresos como Asunto/tendencias , Humanos , Neuroglía/metabolismo , Neuronas/metabolismo

RESUMEN

Inhibition of Rab-GAP TBC1 domain family member 1 (TBC1D1) reduces body weight and increases energy expenditure in mice. Here, we assessed the possible involvement of GTPase activating protein 21 (ARHGAP21), a Rho-GAP protein, in energy homeostasis. Wild-type and whole-body ARHGAP21-haplodeficient mice were fed either chow or high-fat diet for 10 weeks. These mice were analyzed for body weight, food intake, voluntary physical activity, and energy expenditure by indirect calorimetry. Real-time PCR was performed to determine changes in the expression of hypothalamic-anorexic genes. Whole-body ARHGAP21-haplodeficient mice showed lower body weight and food intake associated with increased energy expenditure. These mice also showed higher expression of hypothalamic-anorexic genes such as POMC and CART. Our data suggest that the reduction in body weight of ARHGAP21-haplodeficient mice was related to alterations in the central nervous system. This suggests a new role for ARHGAP21 in energetic metabolism and prompts us to consider GAP protein members as possible targets for the prevention and treatment of obesity and related diseases.

RESUMEN

Glucocorticoids increase appetite and body weight gain in rats and ovariectomy (OVX) induces obesity, while estrogen (E) replacement attenuates OVX-induced changes. It is known that animals with obesity are more responsive to glucocorticoids anabolic effects than lean ones. This study aimed to evaluate the effects of ovariectomy and the protective role of estradiol on the responses induced by prolonged treatment with corticosterone or dexamethasone on energy homeostasis. For this, female Wistar rats subjected to SHAM or OVX surgery, composing the SHAM, OVX, and OVX + E groups, received water/ETOH or corticosterone (15 mg/l) and water or dexamethasone (0.5 µg/l) as drinking fluid for 28 days. The OVX + E group, since the first day, was daily treated with estradiol (10 µg/0.2 ml/rat SC). OVX induced enhancement of body weight gain, food intake, area of the adipocytes and weight of retroperitoneal adipose tissue, plasma cholesterol and glucose intolerance, with reduction on uterus weight. In OVX animals, treatment with glucocorticoids induced increases on body weight gain, food intake, weight of retroperitoneal adipose tissue, area of adipocytes of retroperitoneal and perigonadal + perirenal fat depots, plasma triglycerides (corticosterone), and glycemic response after GTT (dexamethasone), with minor effects on SHAM group. Estradiol treatment to OVX rats prevented these effects induced by glucocorticoids, in addition to decrease body weight gain, fat accumulation and glucose intolerance, and to increase weight of uterus, triglycerides and free fatty acids plasma levels. These data demonstrate that protection against glucocorticoids-induced anabolic responses in females is eliminated by ovariectomy and estradiol can prevent these responses.

Asunto(s)

Anabolizantes/toxicidad , Estrógenos/farmacología , Glucocorticoides/toxicidad , Intolerancia a la Glucosa/prevención & control , Obesidad/prevención & control , Ovariectomía/efectos adversos , Sustancias Protectoras/farmacología , Animales , Peso Corporal , Femenino , Intolerancia a la Glucosa/etiología , Intolerancia a la Glucosa/patología , Obesidad/etiología , Obesidad/patología , Ratas , Ratas Wistar , Aumento de Peso/efectos de los fármacos

RESUMEN

The hypothalamus plays a major role in the regulation of food intake and energy expenditure. In the last decade, it was demonstrated that consumption of high-fat diets triggers the activation of an inflammatory process in the hypothalamus, inducing neurofunctional alterations and contributing to the development of obesity. Hypoxia-inducible factors (HIFs) are key molecules that regulate cellular responses to inflammation and hypoxia, being essential for the normal cell function and survival. Currently, evidence points to a role of HIF pathway in metabolic regulation that could also be involved in the progression of obesity and metabolic diseases. The challenge is to understand how HIF modulation impacts body mass gain and metabolic disorders such as insulin resistance. Distinct animal models with tissue-specific knocking-out or overexpression of hypoxia signaling pathway genes revealed a cell-specificity in the activation of HIF pathways, and some of them have opposite phenotypes among the various HIFs gain- and loss-of-function mouse models. In this review, we discuss the major findings that provide support for a role of HIF pathway involvement in the regulation of metabolism, especially in glucose and energy homeostasis.

RESUMEN

Eating behavior is controlled by the energy needs of the organism. The need to provide a constant supply of energy to tissues is a homeostatic drive that adjusts feeding behavior to the energetic condition of the organism. On the other hand, food intake also shows a circadian variation synchronized to the light-dark cycle and food availability. Thus, feeding is subjected to both homeostatic and circadian regulation mechanisms that determine the amount and timing of spontaneous food intake in normal conditions. In the present study we contrasted the influence of the homeostatic versus the chronostatic mechanisms on food intake in normal conditions and in response to fasting. A group of rats was subjected to food deprivation under two different temporal schemes. A constant-length 24-h food deprivation started at different times of day resulted in an increased compensatory intake. This compensatory response showed a circadian variation that resembled the rhythm of intake in non-deprived animals. When subjected to fasting periods of increasing length (24-66 h), the amount of compensatory feeding varied according to the time of day in which food was made available, being significantly less when the fast ended in the middle of the light phase or beginning of the dark phase. These oscillatory changes did not have a correlation with variations in the level of glucose or ß-hydroxybutyrate in the blood. The results suggest that the mechanism of homeostatic compensation is modulated chronostatically, presumably as part of the alternation of catabolic and anabolic states matching the daily cycles of activity.

Asunto(s)

Ingestión de Alimentos/fisiología , Ayuno/fisiología , Conducta Alimentaria/fisiología , Homeostasis/fisiología , Animales , Ritmo Circadiano/fisiología , Ingestión de Energía/fisiología , Privación de Alimentos , Masculino , Fotoperiodo , Ratas Wistar