RESUMEN
To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60% less food, compared to that of controls for four or eight weeks, and clinical observations, measurement of body and organ weights, morphological differentiation analysis, clinical pathology, and macroscopic and microscopic examinations were conducted. The body weight decreased depending on the degree of food restriction (FR). Cleavage of the balano-preputial skinfold was delayed, and cell debris in the epididymal lumen was noted as a related finding after four-week FR. Vaginal opening was also delayed, and some histopathological findings, such as absence of corpus luteum in the ovary, mucinous degeneration in the vagina, and immature uterus, were noted after eight-week FR. Erythrocyte count increased after four-week FR, but slightly decreased in males only after eight-week FR, and decreased leukocyte and/or reticulocyte counts, accompanied by related histopathological findings were noted after four- and eight-week FR. In blood chemistry, the levels of total protein including globulin, glucose, triglyceride, and calcium decreased, and sodium and chloride increased after four- and eight-week FR. Increases in activities of aspartate transaminase and lactate dehydrogenase and total bilirubin levels were noted after four-week FR, which were attenuated after eight-week FR. The effects of FR seemed to be more remarkable after four weeks. In drug safety evaluation, findings caused by malnutrition should be considered in juvenile toxicity studies when decreased food consumption is observed.
Asunto(s)
Peso Corporal , Animales , Masculino , Femenino , Tamaño de los Órganos , Ratas , Restricción Calórica/efectos adversos , Factores de Tiempo , Privación de Alimentos/fisiología , Ratas Sprague-Dawley , Ratas WistarRESUMEN
Continuous energy restriction is currently considered the first-line dietary therapy for weight loss in individuals with obesity. Recently, interventions which alter the eating window and time of eating occasions have been explored as means to achieve weight loss and other cardiometabolic improvements such as a reduction in blood pressure, glycaemia, lipids and inflammation. It is unknown, however, whether these changes result from unintentional energy restriction or from other mechanisms such as the alignment of nutrient intake with the internal circadian clock. Even less is known regarding the safety and efficacy of these interventions in individuals with established chronic noncommunicable disease states, such as cardiovascular disease. This review examines the effects of interventions which alter both eating window and time of eating occasions on weight and other cardiometabolic risk factors in both healthy participants and those with established cardiovascular disease. We then summarise the state of existing knowledge and explore future directions of study.
Asunto(s)
Restricción Calórica , Enfermedades Cardiovasculares , Humanos , Restricción Calórica/efectos adversos , Ayuno , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Prevención Secundaria , Pérdida de Peso/fisiologíaRESUMEN
INTRODUCTION: Very low-calorie diets (VLCDs) are used preoperatively in bariatric-metabolic surgery; however, this can lead to physiological ketosis. Euglycemic ketoacidosis is an increasingly recognized complication in diabetic patients on sodium-glucose-cotransporter-2 inhibitors (SGLT2i) undergoing surgery and requires assessment of ketones for diagnosis and monitoring. VLCD induced ketosis may confound monitoring in this group. We aimed to evaluate the influence of VLCD, compared to standard fasting, on perioperative ketone levels and acid-base balance. MATERIALS AND METHODS: Twenty-seven patients were prospectively recruited to the intervention group and 26 to the control group from two tertiary referral centres in Melbourne, Australia. Intervention group patients were severely obese (body mass index) (BMI) (≥35), undergoing bariatric-metabolic surgery, and prescribed 2 wk of VLCD preoperatively. Control group patients underwent general surgical procedures and prescribed standard procedural fasting only. Patients were excluded if diabetic or prescribed SGLT2i. Ketone and acid-base measurements were taken at regular intervals. Univariate and multivariate regression was utilised with significance defined as P < 0.005. CLINICALTRIALS: gov ID: NCT05442918. RESULTS: Patients on VLCD, compared to standard fasting, had an increased median preoperative (0.60 versus 0.21 mmol/L), immediate postoperative (0.99 versus 0.34 mmol/L) and day 1 postoperative (0.69 versus 0.21 mmol/L) ketone level (P < 0.001). Preoperative acid-base balance was normal in both groups, however VLCD patients were found to have a metabolic acidosis immediately postoperatively (pH 7.29 versus pH 7.35) (P = 0.019). Acid-base balance had normalized in VLCD patients on postoperative day 1. CONCLUSIONS: Preoperative VLCD resulted in increased pre- and postoperative ketone levels with immediate postoperative values consistent with metabolic ketoacidosis. This should be considered particularly when monitoring diabetic patients prescribed SGLT2i.
Asunto(s)
Acidosis , Diabetes Mellitus Tipo 2 , Cetosis , Humanos , Acidosis/diagnóstico , Acidosis/etiología , Restricción Calórica/efectos adversos , Restricción Calórica/métodos , Diabetes Mellitus Tipo 2/complicaciones , Cetonas , Cetosis/diagnóstico , Cetosis/etiología , ObesidadRESUMEN
Intermittent fasting entails restricting food intake during specific times of day, days of the week, religious practice, or surrounding clinically important events. Herein, the metabolic and circadian rhythm mechanisms underlying the proposed benefits of intermittent fasting for the cancer population are described. We summarize epidemiological, preclinical, and clinical studies in cancer published between January 2020 and August 2022 and propose avenues for future research. An outstanding concern regarding the use of intermittent fasting among cancer patients is that fasting often results in caloric restriction, which can put patients already prone to malnutrition, cachexia, or sarcopenia at risk. Although clinical trials do not yet provide sufficient data to support the general use of intermittent fasting in clinical practice, this summary may be useful for patients, caregivers, and clinicians who are exploring intermittent fasting as part of their cancer journey for clinical outcomes and symptom management.
Asunto(s)
Neoplasias , Obesidad , Humanos , Ayuno Intermitente , Restricción Calórica/efectos adversos , Dieta Reductora/efectos adversos , Dieta Reductora/métodos , Ritmo Circadiano , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapiaRESUMEN
Caloric restriction (CR) is now a popular lifestyle choice due to its ability in experimental animals to improve lifespan, reduce body weight, and lessen oxidative stress. However, more and more emerging evidence suggests this treatment requires careful consideration because of its detrimental effects on the skeletal system. Experimental and clinical studies show that CR can suppress bone growth and raise the risk of fracture, but the specific mechanisms are poorly understood. Reduced mechanical loading has long been thought to be the primary cause of weight loss-induced bone loss from calorie restriction. Despite fat loss in peripheral depots with calorie restriction, bone marrow adipose tissue (BMAT) increases, and this may play a significant role in this pathological process. Here, we update recent advances in our understanding of the effects of CR on the skeleton, the possible pathogenic role of BMAT in CR-induced bone loss, and some strategies to mitigate any potential side effects on the skeletal system.
Asunto(s)
Tejido Adiposo , Restricción Calórica , Animales , Restricción Calórica/efectos adversosRESUMEN
BACKGROUND: Acromegaly diagnosis is established when plasma levels of IGF-1 are increased and the Oral Glucose Tolerance Test (OGTT) with 75gr of glucose can't suppress Growth Hormone (GH) levels. These two parameters are also useful during follow-up, after surgical/radiologic therapy and/or during medical therapy. CASE PRESENTATION: A 29-year-old woman was diagnosed with acromegaly after a severe headache. Previous amenorrhea and facial and acral changes were noticed. A pituitary macroadenoma was found, biochemical evaluation was in agreement with the suspected acromegaly and a transsphenoidal adenectomy was performed. As the disease recurred, a surgical reintervention and radiosurgery (Gamma Knife, 22 Gy) were necessary. No normalization of IGF-1 was achieved during three years after radiosurgery. Surprisingly, then, and although clinical features seemed getting worse, IGF-1 levels became consistently controlled to 0.3-0.8 times the upper limit of the reference range. Questioned, the patient referred that she was following an intermittent fasting dietary plan. However, based on the dietary questionnaire, she was found to be under severe caloric restriction. First OGTT (under caloric restriction) showed absence of GH suppression and an IGF-1 value of 234 ng/dL (Reference Range 76-286 ng/mL). A second OGTT, one month after an eucaloric diet was instituted, showed an increased IGF-1 of 294 ng/dL, maintaining an unsuppressed, yet less elevated, GH. CONCLUSIONS: GHRH/GH/IGF-1 axis controls somatic growth. Regulation is complex, and nutrition status and feeding pattern have a recognized role. Like systemic inflammation or chronic liver disease, fasting and malnutrition decrease the expression of hepatic GH receptors, with consequent reduction of IGF-1 levels, through resistance to GH. This clinical report shows that caloric restriction may represent a pitfall in acromegaly follow-up.
Asunto(s)
Adenoma , Restricción Calórica , Adenoma Hipofisario Secretor de Hormona del Crecimiento , Adulto , Femenino , Humanos , Acromegalia/sangre , Acromegalia/diagnóstico , Acromegalia/cirugía , Restricción Calórica/efectos adversos , Restricción Calórica/métodos , Estudios de Seguimiento , Hormona de Crecimiento Humana/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/etiología , Adenoma Hipofisario Secretor de Hormona del Crecimiento/sangre , Adenoma Hipofisario Secretor de Hormona del Crecimiento/diagnóstico , Adenoma Hipofisario Secretor de Hormona del Crecimiento/cirugía , Adenoma/sangre , Adenoma/diagnóstico , Adenoma/cirugía , Reoperación , Radiocirugia/métodosRESUMEN
Pain perception provides evolutionary advantages by enhancing the probability of survival, but chronic pain continues to be a significant global health concern in modern society. Various factors are associated with pain alteration. Accumulating evidence has revealed that obesity correlates with enhanced pain perception, especially in chronic pain individuals. Existing dietary patterns related to obesity are primarily high-fat diets (HFD) and calorie restriction (CR) diets, which induce or alleviate obesity separately. HFD has been shown to enhance nociception while CR tends to alleviate pain when measuring pain outcomes. Herein, this review mainly summarizes the current knowledge of the effects of HFD and CR on pain responses and underlying molecular mechanisms of the immunological factors, metabolic regulation, inflammatory processes, Schwann cell (SC) autophagy, gut microbiome, and other pathophysiological signaling pathways involved. This review would help to provide insights on potential nonpharmacological strategies of dietary patterns in relieving pain.
Asunto(s)
Restricción Calórica , Dolor Crónico , Humanos , Restricción Calórica/efectos adversos , Dieta Alta en Grasa/efectos adversos , ObesidadRESUMEN
Maternal nutrition during embryonic development and lactation influences multiple aspects of offspring health. Using mice, this study investigates the effects of maternal caloric restriction (CR) during mid-gestation and lactation on offspring neonatal development and on adult metabolic function when challenged by a high fat diet (HFD). The CR maternal model produced male and female offspring that were significantly smaller, in terms of weight and length, and females had delayed puberty. Adult offspring born to CR dams had a sexually dimorphic response to the high fat diet. Compared to offspring of maternal control dams, adult female, but not male, CR offspring gained more weight in response to high fat diet at 10 weeks. In adipose tissue of male HFD offspring, maternal undernutrition resulted in blunted expression of genes associated with weight gain and increased expression of genes that protect against weight gain. Regardless of maternal nutrition status, HFD male offspring showed increased expression of genes associated with progression toward nonalcoholic fatty liver disease (NAFLD). Furthermore, we observed significant, sexually dimorphic differences in serum TSH. These data reveal tissue- and sex-specific changes in gene and hormone regulation following mild maternal undernutrition, which may offer protection against diet induced weight gain in adult male offspring.
Asunto(s)
Dieta Alta en Grasa , Desnutrición , Fenómenos Fisiologicos Nutricionales Maternos , Efectos Tardíos de la Exposición Prenatal , Aumento de Peso , Animales , Femenino , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratones Endogámicos C57BL , Restricción Calórica/efectos adversos , Animales Recién Nacidos , LactanciaRESUMEN
The association of obesity with changes in bone mass is not clear. Obese individuals tend to have an increased bone mineral density, but other studies have shown that obesity is a major risk factor for fractures. The mechanisms of bone response during a weight loss therapy as well as the possible osteoprotective effect of exercise should be analyzed. The aim of this study was to test the effects of a weight-loss program based on the combination of caloric restriction and/or a mixed training protocol on different parameters of bone morphology and functionality in a DIO rat model. Three stages were established over a 21-week period (obesity induction 0-12 w, weight loss intervention 12-15 w, weight maintenance intervention 15-21 w) in 88 male Sprague Dawley rats. Bone microarchitecture, total mineral and elemental composition, and bone metabolism parameters were assessed. Weight loss interventions were associated to healthy changes in body composition, decreasing body fat and increasing lean body mass. On the other hand, obesity was related to a higher content of bone resorption and inflammatory markers, which was decreased by the weight control interventions. Caloric restriction led to marked changes in trabecular microarchitecture, with a significant decrease in total volume but no changes in bone volume (BV). In addition, the intervention diet caused an increase in trabeculae number and a decrease in trabecular spacing. The training protocol increased the pore diameter and reversed the changes in cortical porosity and density of BV induced by the high protein diet at diaphysis level. Regarding the weight-maintenance stage, diminished SMI values indicate the presence of more plate-like spongiosa in sedentary and exercise groups. In conclusion, the lifestyle interventions of caloric restriction and mixed training protocol implemented as weight loss strategies have been effective to counteract some of the deleterious effects caused by a dietary induction of obesity, specifically in trabecular bone morphometric parameters as well as bone mineral content.
Asunto(s)
Restricción Calórica , Hueso Esponjoso , Animales , Densidad Ósea , Restricción Calórica/efectos adversos , Hueso Esponjoso/metabolismo , Masculino , Minerales/farmacología , Obesidad/metabolismo , Ratas , Ratas Sprague-Dawley , Pérdida de PesoRESUMEN
OBJECTIVES: The aims of this study were to explore the safety and effectiveness of alternate-day fasting in Chinese people and to compare weight loss outcomes and safety when consuming a high-protein (HP) versus a normal protein (NP) diet versus a nutritional meal replacement (MR) on fasting days. METHODS: This was a randomized, open, parallel-controlled, interventional, exploratory trial, that included a 3-d run-in period and a 28-d intervention period. Adult participants without restriction of body mass index (N = 60) were randomly assigned to three alternative-day fasting (ADF) intervention groups: group HP, group NP, and group MR. The primary outcome was weight change from baseline at 28 d. RESULTS: Overall participants lost an average of 2.53 kg. Mean triacylglycerols, total cholesterol, and low-density lipoprotein were significantly reduced by 0.10, 0.15, and 0.11 mmol/L, respectively. The mean hunger scale on day 1 of fasting was 18.73 at breakfast and 45.25 at dinner. The mean hunger scale on the last day of fasting decreased significantly, to 10.89 at breakfast and 18.93 at dinner. Weight loss of groups HP, NP, and MR were 2.16, 2.63, and 2.94 kg, respectively; groups did not differ significantly (P = 0.841). The most common adverse events were dizziness, heart palpitations, and fatigue. CONCLUSIONS: ADF is an effective, short-term weight loss strategy that was tolerated by most Chinese participants. We suggest that dietary patterns during fasting days is less important, and that calorie restriction during those days should be the focus.
Asunto(s)
Ayuno , Obesidad , Adulto , Índice de Masa Corporal , Restricción Calórica/efectos adversos , Humanos , Pérdida de PesoRESUMEN
Long non-coding RNAs (lncRNAs) play important biological roles. Here, the roles of the lncRNA KCNQ1OT1 in cellular senescence and calorie restriction were determined. KCNQ1OT1 knockdown mediated various senescence markers (increased senescence-associated ß-galactosidase staining, the p53-p21Cip1/WAF1 pathway, H3K9 trimethylation, and expression of the senescence-associated secretory phenotype) and reactive oxygen species generation via CK2α downregulation in human cancer HCT116 and MCF-7 cells. Additionally, KCNQ1OT1 was downregulated during replicative senescence, and its silencing induced senescence in human lung fibroblast IMR-90 cells. Additionally, an miR-760 mimic suppressed KCNQ1OT1-mediated CK2α upregulation, indicating that KCNQ1OT1 upregulated CK2α by sponging miR-760. Finally, the KCNQ1OT1-miR-760 axis was involved in both lipopolysaccharide-mediated CK2α reduction and calorie restriction (CR)-mediated CK2α induction in these cells. Therefore, for the first time, this study demonstrates that the KCNQ1OT1-miR-760-CK2α pathway plays essential roles in senescence and CR, thereby suggesting that KCNQ1OT1 is a novel therapeutic target for an alternative treatment that mimics the effects of anti-aging and CR.
Asunto(s)
Restricción Calórica/efectos adversos , Fibroblastos/citología , MicroARNs/genética , Neoplasias/genética , Quinasa de la Caseína II/genética , Línea Celular , Senescencia Celular , Regulación hacia Abajo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Técnicas de Silenciamiento del Gen , Células HCT116 , Humanos , Lipopolisacáridos/efectos adversos , Células MCF-7 , Neoplasias/metabolismo , Canales de Potasio con Entrada de Voltaje/genética , Especies Reactivas de Oxígeno/metabolismo , Fenotipo Secretor Asociado a la Senescencia/efectos de los fármacosRESUMEN
Importance: Sulfur-metabolizing bacteria that reduce dietary sulfur to hydrogen sulfide have been associated with colorectal cancer (CRC). However, there are limited studies investigating the association between diet and sulfur-metabolizing bacteria in the development of CRC. Objective: To develop a dietary score that correlates with gut sulfur-metabolizing bacteria and to examine its association with CRC risk. Design, Setting, and Participants: This prospective cohort study included data from the Health Professionals Follow-up Study (1986-2014), Nurses' Health Study (1984-2016), and Nurses' Health Study II (1991-2017). Participants were US male health professionals and female registered nurses who were free of inflammatory bowel disease and cancer at baseline, with a subsample of participants who provided stool samples from 2012 to 2014. Statistical analysis was conducted from September 1, 2020, to June 1, 2021. Exposure: A dietary pattern, assessed by a food-frequency questionnaire, that most correlated with 43 sulfur-metabolizing bacteria identified through taxonomic and functional profiling of gut metagenome data. Main Outcomes and Measures: Incident CRC. Results: Among 214â¯797 participants comprising 46â¯550 men (mean [SD] age at baseline, 54.3 [9.7] years) and 168â¯247 women (mean [SD] age at baseline, 43.0 [9.2] years), 3217 incident cases of CRC (1.5%) were documented during 5â¯278â¯048 person-years of follow-up. The sulfur microbial diet, developed in a subsample of 307 men (mean [SD] age, 70.5 [4.3] years) and 212 women (mean [SD] age, 61.0 [3.8] years), was characterized by high intakes of low-calorie beverages, french fries, red meats, and processed meats and low intakes of fruits, yellow vegetables, whole grains, legumes, leafy vegetables, and cruciferous vegetables. After adjustment for other risk factors, greater adherence to the sulfur microbial diet was associated with an increased risk of CRC, with a hazard ratio (HR) of 1.27 (95% CI, 1.12-1.44) comparing the highest vs the lowest quintile of the diet score (linear trend of diet score quintiles; P < .001 for trend). When assessed by anatomical subsites, greater adherence to the sulfur microbial diet was positively associated with distal CRC (HR, 1.25; 95% CI, 1.05-1.50; P = .02 for trend) but not proximal colon cancer (HR, 1.13; 95% CI, 0.93-1.39; P = .19 for trend). Conclusions and Relevance: Adherence to the sulfur microbial diet was associated with an increased risk of CRC, suggesting a potential mediating role of sulfur-metabolizing bacteria in the associaton between diet and CRC. Further research is needed to confirm these findings and to determine the underlying mechanisms.
Asunto(s)
Neoplasias Colorrectales/epidemiología , Dieta Saludable/estadística & datos numéricos , Dieta/efectos adversos , Bacterias Reductoras del Azufre , Azufre/metabolismo , Adulto , Anciano , Restricción Calórica/efectos adversos , Neoplasias Colorrectales/etiología , Dieta/métodos , Encuestas sobre Dietas , Heces/microbiología , Conducta Alimentaria/fisiología , Femenino , Estudios de Seguimiento , Frutas , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Carne Roja/efectos adversos , Factores de Riesgo , VerdurasRESUMEN
Caloric restriction has been known for nearly a century to extend life span and delay age-associated pathology in laboratory animals. More recently, alternative "antiaging" diet modalities have been described that provide new mechanistic insights and potential clinical applications. These include intermittent fasting, fasting-mimicking diets, ketogenic diets, time-restricted feeding, protein restriction, and dietary restriction of specific amino acids. Despite mainstream popularization of some of these diets, many questions remain about their efficacy outside of a laboratory setting. Studies of these interventions support at least partially overlapping mechanisms of action and provide insights into what appear to be highly conserved mechanisms of biological aging.
Asunto(s)
Envejecimiento , Dieta , Salud , Longevidad , Aminoácidos , Animales , Restricción Calórica/efectos adversos , Dieta/efectos adversos , Modas Dietéticas , Dieta Cetogénica/efectos adversos , Dieta con Restricción de Proteínas/efectos adversos , Ayuno/efectos adversos , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
This review examines the effects of two popular intermittent fasting regimens on sleep in adults with overweight and obesity. Specifically, the effects of time restricted eating (TRE; eating all food within a 4-10 h window) and alternate day fasting (ADF; 600 kcal fast day alternated with ad libitum feast day) on sleep quality, sleep duration, sleep latency, sleep efficiency, insomnia severity, and risk of obstructive sleep apnea, will be summarized. The role of weight loss will also be discussed. Results from our review reveal that the majority of these trials produced weight loss in the range of 1-6% from baseline. Sleep quality and sleep duration remained unaltered with TRE and ADF, as assessed by the Pittsburgh Sleep Quality Index (PSQI). The effects of intermittent fasting on sleep latency and sleep efficiency are mixed, with one study showing worsening of these parameters, and others showing no effect. Insomnia severity and the risk of obstructive sleep apnea remained unchanged in the trials assessing these metrics. Taken together, these preliminary findings suggest that TRE and ADF produce mild to moderate weight loss (1-6%) but their effects on sleep remain unclear. Solid conclusions are difficult to establish since participants in the studies had healthy sleep durations and no clinical insomnia at baseline, leaving little room for improvement in these metrics. Moreover, none of the trials were adequately powered to detect statistically significant changes in any measure of sleep. Future well-powered trials, conducted in individuals with diagnosed sleep disturbances, will be necessary to elucidate the effect of these popular diets on sleep.
Asunto(s)
Restricción Calórica/efectos adversos , Ayuno/efectos adversos , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Sueño/fisiología , Adulto , Restricción Calórica/métodos , Ensayos Clínicos como Asunto , Ayuno/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/dietoterapia , Sobrepeso/complicaciones , Sobrepeso/dietoterapia , Apnea Obstructiva del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Pérdida de Peso/fisiologíaRESUMEN
We studied whether myo-inositol supplementation throughout lactation, alone and combined with leptin, may reverse detrimental effects on hypothalamic structure and function caused by gestational calorie gestation (CR) in rats. Candidate early transcript-based biomarkers of metabolic health in peripheral blood mononuclear cells (PBMC) were also studied. Offspring of dams exposed to 25% gestational CR and supplemented during lactation with physiological doses of leptin (CR-L), myo-inositol (CR-M), the combination (CR-LM), or the vehicle (CR-V) as well as control rats (CON-V) were followed and sacrificed at postnatal day 25. Myo-inositol and the combination increased the number of neurons in arcuate nucleus (ARC) (only in females) and paraventricular nucleus, and myo-inositol (alone) restored the number of αMSH+ neurons in ARC. Hypothalamic mRNA levels of Lepr in CR-M and Insr in CR-M and CR-LM males were higher than in CR-V and CON-V, respectively. In PBMC, increased expression levels of Lrp11 and Gls in CR-V were partially normalized in all supplemented groups (but only in males for Gls). Therefore, myo-inositol supplementation throughout lactation, alone and combined with leptin, reverts programmed alterations by fetal undernutrition on hypothalamic structure and gene expression of potential early biomarkers of metabolic health in PBMC, which might be attributed, in part, to increased leptin sensitivity.
Asunto(s)
Animales Lactantes/fisiología , Restricción Calórica/efectos adversos , Hipotálamo/embriología , Inositol/administración & dosificación , Efectos Tardíos de la Exposición Prenatal , Animales , Suplementos Dietéticos , Femenino , Hipotálamo/química , Hipotálamo/citología , Lactancia/fisiología , Leptina , Leucocitos Mononucleares/química , Masculino , Embarazo , ARN Mensajero/análisis , Ratas , Ratas Wistar , Receptores de Leptina/genéticaRESUMEN
Short-term calorie reduction (SCR) requires individuals to reduce their calorie intake to less than 50% of normal requirements and has shown good tolerance and potential benefits in prior studies addressing gynecological cancer patients. More studies are needed to further confirm its safety, feasibility, and effects in patients with different cancers, including hematological malignancies. This pilot cohort study with a matched-pair comparison group was registered at ClinicalTrails.gov [201810112RIND]. Adult patients diagnosed with advanced-stage diffuse large-B cell lymphoma were recruited (SCR group) and matched with one comparison patient (comparison group), each in a manner blinded to their outcomes. The SCR group undertook at least two cycles of 48 h water fast along with their chemotherapy R-CHOP. Descriptive analysis and generalized estimating equations were used to analyze the data. Six participants completed multiple cycles of SCR and were compared to their six counterparts in the comparison group. The results showed that SCR is safe and feasible in terms of a high compliance rate and stable nutritional status. The SCR was associated with benefits in post-chemotherapy hematological parameters (i.e., erythrocyte [p < 0.001] and lymphocyte counts [p < 0.001]). More randomized controlled trials are needed to validate the effects of SCR on different types of cancer populations.
Asunto(s)
Restricción Calórica/métodos , Quimioterapia de Inducción/métodos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Restricción Calórica/efectos adversos , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Estudios de Factibilidad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/dietoterapia , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Proyectos Piloto , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/uso terapéutico , Rituximab/administración & dosificación , Rituximab/efectos adversos , Rituximab/uso terapéutico , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversos , Vincristina/uso terapéuticoRESUMEN
Weight loss contributes to an increased risk of hip fracture, especially in postmenopausal women. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation could diminish the adverse effect of weight loss on bone health. The aim of this randomized, placebo-controlled, double-blind parallel trial was to investigate the effect of caloric restriction and n-3 PUFA supplement intake on osteogenic markers (carboxylated osteocalcin (Gla-OC); procollagen I N-terminal propeptide (PINP)), as well as a bone resorption marker (C-terminal telopeptide of type I collagen (CTX-I)) in a serum of 64 middle aged individuals (BMI 25-40 kg/m2) with abdominal obesity. Bone remodeling, metabolic and inflammatory parameters and adipokines were determined before and after 3 months of an isocaloric diet (2300-2400 kcal/day) or a low-calorie diet (1200 kcal/day for women and 1500 kcal/day for men) along with n-3 PUFA (1.8 g/day) or placebo capsules. CTX-I and adiponectin concentrations were increased following 7% weight loss independently of supplement use. Changes in CTX-I were positively associated with changes in adiponectin level (rho = 0.25, p = 0.043). Thus, an increase in serum adiponectin caused by body weight loss could adversely affect bone health. N-3 PUFAs were without effect.
Asunto(s)
Biomarcadores/sangre , Remodelación Ósea/fisiología , Resorción Ósea/etiología , Restricción Calórica/efectos adversos , Ácidos Grasos Omega-3/administración & dosificación , Obesidad Abdominal/terapia , Adiponectina/sangre , Adulto , Anciano , Remodelación Ósea/efectos de los fármacos , Resorción Ósea/prevención & control , Colágeno Tipo I/sangre , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/sangre , Osteocalcina/sangre , Fragmentos de Péptidos/sangre , Péptidos/sangre , Placebos , Procolágeno/sangre , Pérdida de PesoRESUMEN
The role that genetic background may play in the responsiveness of organisms to interventions such as caloric restriction (CR) is underappreciated but potentially important. We investigated the impact of genetic background on a suite of metabolic parameters in female recombinant inbred ILSXISS mouse strains previously reported to show divergent lifespan responses to 40% CR (TejJ89-lifespan extension; TejJ48-lifespan unaffected; TejJ114-lifespan shortening). Body mass was reduced across all strains following 10 months of 40% CR, although this loss (relative to ad libitum controls) was greater in TejJ114 relative to the other strains. Gonadal white adipose tissue (gWAT) mass was similarly reduced across all strains following 40% CR, but brown adipose tissue (BAT) mass increased only in strains TejJ89 and TejJ48. Surprisingly, glucose tolerance was improved most notably by CR in TejJ114, while both strains TejJ89 and TejJ114 were hyperinsulinemic following CR relative to their AL controls. We subsequently undertook an unbiased metabolomic approach in gWAT and BAT tissue derived from strains TejJ89 and TejJ114 mice under AL and 40% CR. In gWAT from TejJ89 a significant reduction in several long chain unsaturated fatty acids was observed following 40% CR, but gWAT from TejJ114 appeared relatively unresponsive to CR with far fewer metabolites changing. Phosphatidylethanoloamine lipids within the BAT were typically elevated in TejJ89 following CR, while some phosphatidylglycerol lipids were decreased. However, BAT from strain TejJ114 again appeared unresponsive to CR. These data highlight strain-specific metabolic differences exist in ILSXISS mice following 40% CR. We suggest that precisely how different fat depots respond dynamically to CR may be an important factor in the variable longevity under 40% CR reported in these mice.
Asunto(s)
Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Restricción Calórica/efectos adversos , Metabolómica/métodos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Índice de Masa Corporal , Femenino , Prueba de Tolerancia a la Glucosa , Longevidad , Ratones , Ratones Endogámicos , Fosfatidiletanolaminas/metabolismo , Fosfatidilgliceroles/metabolismoRESUMEN
SirT1 plays a crucial role in the regulation of some of the caloric restriction (CR) responsive biological pathways. Aging suppresses SirT1 gene expression in skeletal muscle, suggesting that aging may affect the role of CR in muscle. To determine the role of SirT1 in the regulation of CR regulated pathways in skeletal muscle, we performed high-throughput RNA sequencing using total RNA isolated from the skeletal muscles of young and aged wild-type (WT), SirT1 knockout (SirT1-KO), and SirT1 overexpression (SirT1-OE) mice fed to 20 wk ad libitum (AL) or 40% CR diet. Our data show that aging repressed the global gene expression profile, which was restored by CR via upregulating transcriptional and translational process-related pathways. CR inhibits pathways linked to the extracellular matrix and cytoskeletal proteins regardless of aging. Mitochondrial function and muscle contraction-related pathways are upregulated in aged SirT1 KO mice following CR. SirT1 OE did not affect whole-body energy expenditure or augment skeletal muscle insulin sensitivity associated pathways, regardless of aging or diet. Overall, our RNA-seq data showed that SirT1 and CR have different functions and activation of SirT1 by its activator or exercise may enhance SirT1 activity that, along with CR, likely have a better functional role in aging muscle.