Circadian regulation of glucose, lipid, and energy metabolism in humans.

The circadian system orchestrates metabolism in daily 24-hour cycles. Such rhythms organize metabolism by temporally separating opposing metabolic processes and by anticipating recurring feeding-fasting cycles to increase metabolic efficiency. Although animal studies demonstrate that the circadian system plays a pervasive role in regulating metabolism, it is unclear how, and to what degree, circadian research in rodents translates into humans. Here, we review evidence that the circadian system regulates glucose, lipid, and energy metabolism in humans. Using a range of experimental protocols, studies in humans report circadian rhythms in glucose, insulin, glucose tolerance, lipid levels, energy expenditure, and appetite. Several of these rhythms peak in the biological morning or around noon, implicating earlier in the daytime is optimal for food intake. Importantly, disruptions in these rhythms impair metabolism and influence the pathogenesis of metabolic diseases. We therefore also review evidence that circadian misalignment induced by mistimed light exposure, sleep, or food intake adversely affects metabolic health in humans. These interconnections among the circadian system, metabolism, and behavior underscore the importance of chronobiology for preventing and treating type 2 diabetes, obesity, and hyperlipidemia

Are the therapeutic strategies in anorexia of ageing effective on nutritional status? A systematic review with meta-analysis

BACKGROUND: Anorexia of ageing (AA) may be considered as a risk factor for frailty and has an important impact on quality of life, morbidity and mortality. METHODS: A systematic review and a meta-analysis were performed to summarise the results from several trials on the effectiveness of treatments in AA, as associated with depression, sensory impairment of taste and smell, decreased appetite or early satiety, and disability. Eligible studies were required to report baseline and follow-up values, the mean change (∆-change) from baseline, and/or the mean difference among intervention groups versus control group, concerning food intake (kcal/daily) and/or nutritional outcomes, such as body weight, body mass index, albumin and Mini Nutritional Assessment. RESULTS: The systematic review included 20 papers based on different therapeutic approaches concerning food intake and/or nutritional outcomes. The results of the meta-analysis indicate that the interventions for AA have an important impact on body weight [+1.59 kg; 95% confidence interval (CI) = 1.48-+1.71 kg; P < 0.001) and on energy intake (+56.09 kcal; 95% CI = -54.05 to +166.25 kcal; P = 0.32). Regarding secondary outcomes, it was not possible to meta-analyse the limited amount of data availab le. CONCLUSIONS: The different variants of AA need to be defined because diverse therapeutic approaches are available. A more precise definition of the functional impairments associated with AA may allow a more correct decision about the most appropriate therapy to be prescribed. Moreover, this may allow for a more effective performance of the different therapeutic approaches once they are better targeted to the different scenarios of AA

Body composition, IGF1 status, and physical functionality in nonagenarians: implications for osteosarcopenia

OBJECTIVES: Body composition alterations occur during aging. The purpose of the present analysis was to explore the functional consequences of the overlap of sarcopenia and osteoporosis, and the potential role of insulin-like growth factor 1 (IGF1) in their development in the oldest old. SETTING AND PARTICIPANTS: Eighty-seven nonagenarians from the Louisiana Healthy Aging Study were included. MEASURES: The definition of sarcopenia was based on appendicular lean mass (ALM). Osteoporosis was diagnosed based on bone mineral density (BMD) T score. Four phenotypes were compared: (1) healthy body composition, that is, nonosteoporotic nonsarcopenic (CO, control group), (2) osteoporotic (O, low BMD T score), (3) sarcopenic (S, low ALM), and (4) osteosarcopenic (OS, low BMD T score and low ALM). Sex- and age-specific IGF1-Standard Deviation Scores (SDS) were calculated. The Continuous Scale-Physical Functional Performance (CS-PFP) test was performed. RESULTS: In OS men, IGF1-SDS values (-0.61 ±0.37 vs -0.04 ± 0.52, P = .02) were lower than those in CO males (control group), whereas IGF1-SDS were similar in the 4 body composition phenotypes in women. In men only, ALM was positively associated with IGF1-SDS values (P = .01) independent of age and C-reactive protein concentration. Regarding bone health, we found no association between IGF1-SDS values and BMD. IGF1-SDS was not associated with functional performance (CS-PFP) in men and women. CONCLUSIONS/IMPLICATIONS: IGF1 sensitivity in skeletal muscle and bone may differ by sex in the oldest old. IGF1 status did not appear to affect physical functionality. Determinants and clinical and functional characteristics of osteosarcopenia need to be further investigated in order to define conclusive diagnostic criteria

Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity

Background and aim: Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. Methods and results: Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (rho = -0.350, P = 0.005; rho = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (beta = -0.352, P = 0.016). Conclusions: Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved

Amino acids and hypertension in adults

Accumulating evidence suggests a potential role of dietary protein among nutritional factors interfering with the regulation of blood pressure. Dietary protein source (plant versus animal protein), and especially, protein composition in terms of amino acids has been postulated to interfere with mechanisms underlying the development of hypertension. Recently, mounting interest has been directed at amino acids in hypertension focusing on habitual dietary intake and their circulating levels regardless of single amino acid dietary supplementation. The aim of the present review was to summarize epidemiological evidence concerning the connection between amino acids and hypertension. Due to the large variability in methodologies used for assessing amino acid levels and heterogeneity in the results obtained, it was not possible to draw robust conclusions. Indeed, some classes of amino acids or individual amino acids showed non-causative association with blood pressure as well as the incidence of hypertension, but the evidence was far from being conclusive. Further research should be prompted for a thorough understanding of amino acid effects and synergistic actions of different amino acid classes on blood pressure regulation

Overweight and obese patients with nickel allergy have a worse metabolic profile compared to weight matched non-allergic individuals

A lack of balance between energy intake and expenditure due to overeating or reduced physical activity does not seem to explain entirely the obesity epidemic we are facing, and further factors are therefore being evaluated. Nickel (Ni) is a ubiquitous heavy metal implied in several health conditions. Regarding this, the European Food Safety Authority has recently released an alert on the possible deleterious effects of dietary Ni on human health given the current levels of Ni dietary intake in some countries. Pre-clinical studies have also suggested its role as an endocrine disruptor and have linked its exposure to energy metabolism and glucose homeostasis dysregulation. Ni allergy is common in the general population, but preliminary data suggest it being even more widespread among overweight patients. OBJECTIVES: The aim of this study has been to evaluate the presence of Ni allergy and its association with the metabolic and endocrine profile in overweight and obese individuals. METHODS: We have evaluated 1128 consecutive overweight and obese outpatients. 784 were suspected of being allergic to Ni and 666 were assessed for it. Presence of Ni allergy and correlation with body mass index (BMI), body composition, metabolic parameters and hormonal levels were evaluated. RESULTS: We report that Ni allergy is more frequent in presence of weight excess and is associated with worse metabolic parameters and impaired Growth Hormone secretion. CONCLUSIONS: We confirm that Ni allergy is more common in obese patients, and we report for the first time its association with worse metabolic parameters and impaired function of the GH-IGF1 axis in human subjects

Physical activity and hypocaloric diet recovers osteoblasts homeostasis in women affected by abdominal obesity.

Obesity is a multifactorial disease linked to metabolic chronic disorders such as diabetes, and hypertension. Also, it has recently been associated with skeletal alterations and low bone mineral density. We previously demonstrated that exposure of osteoblasts to sera of sedentary subjects affected by obesity alters cell homeostasis in vitro, leading to disruption of intracellular differentiation pathways and cellular activity. Thus, the purpose of the present study has been to evaluate whether sera of sedentary obese women, subjected to physical activity and hypocaloric diet, could recover osteoblast homeostasis in vitro as compared to the sera of same patients before intervention protocol. To this aim, obese women were evaluated at time 0 and after 4, 6, and 12 months of individualized prescribed physical activity and hypocaloric diet. Dual-energy-X-ray absorptiometry measurements were performed at each time point, as well as blood was collected at the same points. Cells were incubated with sera of subjects before and after physical activity as described: obese at baseline and after for 4, 6, and 12 months of physical activity and nutritional protocol intervention. Osteoblasts exposed to sera of patients, who displayed increased lean and decreased fat mass (from 55.5 ± 6.5 to 57.1 ± 5.6% p ≤ 0.05; from 44.5 ± 1.1 to 40.9 ± 2.6% p ≤ 0.01 respectively), showed a time-dependent increase of Wnt/β-catenin signaling, versus cells exposed to sera of obese patients before intervention protocol, suggesting recovery of osteoblast homeostasis upon improvement of body composition. An increase in β-catenin nuclear accumulation and nuclear translocation was also observed, accompanied by an increase in Adiponectin receptor 1 protein expression, suggesting positive effect on cell differentiation program. Furthermore, a decrease in sclerostin amount and an increase of type 1 procollagen amino-terminal-propeptide were depicted as compared to baseline, proportionally to the time of physical activity, suggesting a recovery of bone remodeling modulation and an increase of osteoblast activity induced by improvement of body composition. In conclusion, our results show for the first time that sera of obese sedentary women who increased lean mass and decreased fat mass, by physical activity and hypocaloric diet, rescue osteoblasts differentiation and activity likely due to a reactivation of Wnt/β-catenin-pathway, suggesting that a correct life style can improve skeletal metabolic alteration induced by obesity

Inverse association of circulating SIRT1 and adiposity. A study on underweight, normal weight, and obese patients

Context: Sirtuins (SIRTs) are NAD+-dependent deacetylases, cellular sensors to detect energy availability, and modulate metabolic processes. SIRT1, the most studied family member, influences a number of tissues including adipose tissue. Expression and activity of SIRT1 reduce with weight gain and increase in conditions of starvation. Objective: To focus on SIRT1 plasma concentrations in different conditions of adiposity and to correlate SIRT1 with fat content and distribution, energy homeostasis and inflammation in under-weight, normal-weight, and obese individuals. Materials and Methods: 21 patients with anorexia nervosa, 26 normal-weight and 75 patients with obesity were evaluated. Body fat composition by dual-energy X-ray absorptiometry, ultrasound liver adiposity, echocardiographic epicardial fat thickness (EFT), inflammatory (ESR, CRP, and fibrinogen), and metabolic (FPG, insulin, LDL- and HDL-cholesterol, triglycerides) parameters, calculated basal metabolic rate (BMR) and plasma SIRT1 (ELISA) were measured. Results: SIRT1 was significantly higher in anorexic patients compared to normal-weight and obese patients (3.27 ± 2.98, 2.27 ± 1.13, and 1.36 ± 1.31 ng/ml, respectively). Linear regression models for each predictor variable adjusted for age and sex showed that SIRT1 concentration was inversely and significantly correlated with EFT, fat mass %, liver fat content, BMR, weight, BMI, WC, LDL-cholesterol, insulin, ESR. Stepwise multiple regression analysis revealed that age and EFT were the best independent correlates of SIRT1 (β = -0.026 ± 0.011, p = 0.025, and β = -0.516 ± 0.083, p < 0.001, respectively). Conclusions: Plasma SIRT1 shows a continuous pattern that inversely follows the whole spectrum of adiposity. SIRT1 significantly associates with EFT, a strong index of visceral fat phenotype, better than other indexes of adiposity studied here

What are the risk factors for malnutrition in older-aged institutionalized adults?

Malnutrition is common in older adults and is associated with functional impairment, reduced quality of life, and increased morbidity and mortality. The aim of this study was to explore the association between health (including depression), physical functioning, disability and cognitive decline, and risk of malnutrition. Participants were recruited from nursing homes in Italy and completed a detailed multidimensional geriatric evaluation. All the data analyses were completed using Stata Version 15.1. The study included 246 participants with an age range of 50 to 102 (80.4 ± 10.5). The sample was characterised by a high degree of cognitive and functional impairment, disability, and poor health and nutritional status (according to Mini Nutritional Assessment (MNA), 38.2% were at risk for malnutrition and 19.5% were malnourished). Using a stepwise linear regression model, age (B = −0.043, SE = 0.016, p = 0.010), depression (B = −0.133, SE = 0.052, p = 0.011), disability (B = 0.517, SE = 0.068, p &lt; 0.001), and physical performance (B = −0.191, SE = 0.095, p = 0.045) remained significantly associated with the malnutrition risk in the final model (adjusted R-squared = 0.298). The logistic regression model incorporating age, depression, disability, and physical performance was found to have high discriminative accuracy (AUC = 0.747; 95%CI: 0.686 to 0.808) for predicting the risk of malnutrition. The results of the study confirm the need to assess nutritional status and to investigate the presence of risk factors associated with malnutrition in order to achieve effective prevention and plan a better intervention strategy