Human Energy Balance Research Articles

Programming effects of FTO in the development of obesity

It is becoming increasingly recognized that early-life nutritional, metabolic and environmental factors can have a long-term impact on the early onset of obesity, type 2 diabetes and cardiovascular diseases. Numerous experimental and epidemiological observations support the concept that an individual's response to their adult lifestyle and nutritional environment depends not only on their genetic susceptibility but also on their previous early-life experiences. The current research challenge is to determine the primary pathways contributing to 'non- or epi-genetic' causes of excess adult weight gain and adiposity. Evidence from the fields of genetic epidemiology, life course modelling and diet-induced foetal programming all support a role for the FTO gene in this complex biological interaction. It may provide a missing link in the developmental regulation of energy metabolism. Our review therefore considers the role of the FTO gene in the early-life determination of body weight, body composition and energy balance. We will summarize current knowledge on FTO biology combining human genetic epidemiology, molecular models and findings from animal studies. Notably, we will focus on the role of FTO in energy balance in humans, the importance of FTO polymorphisms in childhood growth and the impact of foetal nutrition. Ultimately, we propose a new hypothesis for future research designed to understand the role of FTO in setting gene expression in metabolically active tissues.

Quantification of climate-tourism potential for Athens, Greece – Recent and future climate simulations

<p>The aim of this paper is to present in a useful and understandable way how climatic change could be interpreted for tourism and recreation. Future climate change conditions are analyzed using the Climate Version of the Local Model (CLM) based on the COSMO model, which is currently used – among other weather services – by the DWD (Deutscher Wetterdienst) for operational weather forecast. The climate simulations concern the future periods 2021-2050 and 2071-2100 against the reference period 1961-1990, under A1B scenario. Based on regional climate simulations, the analysis for tourism can be performed using the Climate-Tourism-Information-Scheme (CTIS). The CTIS contains detailed climate information, which can be used by tourists to anticipate thermal comfort, aesthetical and physical conditions for planning their vacations. Furthermore, the Physiologically Equivalent Temperature (PET), which is one of the most popular physiological thermal indices derived from the human energy balance, is used in the analysis in order to describe the effect of climate. The future simulations concerning PET and CTIS for the area for Athens have been exemplary used, in order to consider them for tourism industry and local authorities for tourism planning.</p>

Assessment of bioclimatic conditions on Crete Island, Greece

The objective of this study was to assess and analyze the human bioclimatic conditions of Crete Island, by applying two human thermal indices: physiological equivalent temperature (PET), derived from the Munich Energy-balance Model for Individuals human energy balance model, and Universal Thermal Climate Index (UTCI), based on the Fiala multi-node model of human thermoregulation. Human bioclimatic studies provide a framework for considering the effects of climatic conditions on human beings and highlighting the social/economic factors that mitigate or amplify the consequences of environmental changes. In order to estimate the thermal effect of the environment on the human body, it has been considered that the total effects of all thermal components, not only of individual parameters, should be taken into account. The climatic data (air temperature, relative humidity, cloudiness, wind speed) used in this study were acquired from the archives of the Hellenic National Meteorological Service, regarding ten meteorological stations in Crete Island. These data, covering the 30-year period 1975–2004, were used for the calculation of PET and UTCI in order to assess thermo-physiological stress levels. The findings of this analysis, such as bioclimatic diagrams, temporal and spatial distributions of PET and UTCI as well as trends and variability, will help stake holders to understand and interpret the island’s current bioclimate, in order to make any necessary adaptations and become more resilient to the foreseen climate change.

The Effect of Relative Humidity on Physiological Equivalent Temperature in Hot Environment

The important meteorological parameter affecting the human energy balance in heat strain condition is the relative humidity. The aim of this paper is to investigate the effect of relative humidity on human heat comfort. In this paper, the physiological equivalent temperature (PET) calculating program was corrected. The relationship between PET and relative humiditythermal state of human body on a typical hot day was analyzed. The results show that: Sweating is the most effective thermoregulatory process when the body is in a condition of heat strain; High water vapor pressure can restrain sweat evaporation and effect human heat balance in hot environment; The PET value increases rapidly as relative humidity over "threshold value" in hot environment, and the "threshold value" is different in various heat stain condition; The PET calculated by modified program agrees well with heat thermal sensation of people in hot-humidity environment.

Cell-Autonomous Regulation of Brown Fat Identity Gene UCP1 by Unliganded Vitamin D Receptor

White adipose tissue stores energy in the form of lipids, and brown adipose tissue expends energy via uncoupled fatty acid oxidation, which leads to the generation of heat. Obesity reflects an imbalance between energy storage and energy expenditure and is strongly associated with metabolic and cardiovascular disease. Therefore, there are important medical and biological implications for elucidating the mechanisms that promote energy expenditure in humans. Animal models with altered vitamin D receptor (VDR) expression have changes in energy expenditure. However, the specific mechanism for this effect has not been elucidated and the relevance for humans is unclear. Here we show, using human patient samples from individuals with hereditary vitamin D resistant rickets, that the VDR directly inhibits the expression of uncoupling protein-1 (UCP1), the critical protein for uncoupling fatty acid oxidation in brown fat and burning energy. The inhibition is enforced by VDR occupancy of a negative response element in the promoter proximal region of the UCP1 gene. Deletion of VDR increases UCP1 expression and results in a "browning" of adipocytes. Importantly, we found that this process occurs cell autonomously and is independent of the physiologic VDR hormone ligand, 1,25-dihydroxyvitamin D. These results identify a mechanism for modulating energy balance in humans.

Brown Adipose Tissue: Research Milestones of a Potential Player in Human Energy Balance and Obesity

Obesity and diabetes mellitus are worldwide epidemics driven by the disruption in energy balance. In recent years, it was discovered that functional brown adipose tissue (BAT), once thought to exist mainly in infants, is present in adults, and can be detected during cold stimulation, and is associated with decreased adiposity. Brown fat pads were shown to be highly vascularized and metabolically active and on stimulation, they caused enhanced energy expenditure and increased glucose and fatty acid uptake. These observations drew attention to the possibility that nonshivering thermogenesis mediated by activation of BAT might be important in human energy balance and a potential tool to counter obesity. Recent investigations have revealed significant advances in the understanding of the role of BAT-mediated thermogenesis, uncovering essential knowledge on the origin, differentiation, activation, and regulation of BAT in both murine models and humans. In addition to classic BAT depots, transformation of white adipocytes into brown-like adipocytes, and the development of "beige" cells from distinct precursors, were demonstrated in different animal models and resulted in increased thermogenic activity. Several transcription factors, activating proteins, and hormones are increasingly identified as regulating the development and function of both brown-like adipocytes and classic brown fat pads. This review will summarize the evolution of research on BAT in humans, in light of the renewed scientific interest and growing body of evidence showing that recruitment and activation of BAT and browning of white adipose tissue can affect energy expenditure and may be a future feasible target in the treatment of metabolic diseases.

Brown Fat Activation Mediates Cold-Induced Thermogenesis in Adult Humans in Response to a Mild Decrease in Ambient Temperature

The contribution of brown adipose tissue (BAT) to the energy balance in humans exposed to sustainable cold has not been completely established, partially because of measurement limitations of both BAT activity and energy expenditure (EE). The objective of the study was to characterize the role of BAT activation in cold-induced thermogenesis (CIT). This study was a single-blind, randomized crossover intervention. The study was conducted at the National Institutes of Health Clinical Center. Thirty-one healthy volunteers participated in the study. The intervention included mild cold exposure. CIT and BAT activation were the main outcomes in this study. Overnight EE measurement by whole-room indirect calorimeter at 24 °C or 19 °C was followed by 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan. After 36 hours, volunteers crossed over to the alternate study temperature under identical conditions. BAT activity was measured in a 3-dimensional region of interest in the upper torso by comparing the uptake at the two temperatures. Twenty-four volunteers (14 males, 10 females) had a complete data set. When compared with 24 °C, exposure at 19 °C resulted in increased EE (5.3 ± 5.9%, P < .001), indicating CIT response and mean BAT activity (10.5 ± 11.1%, P < .001). Multiple regression analysis indicated that a difference in BAT activity (P < .001), age (P = .01), and gender (P = .037) were independent contributors to individual variability of CIT. A small reduction in ambient temperature, within the range of climate-controlled buildings, is sufficient to increase human BAT activity, which correlates with individual CIT response. This study uncovers for the first time a spectrum of BAT activation among healthy adults during mild cold exposure not previously recognized by conventional PET and PET-computed tomography methods. The enhancement of cold-induced BAT stimulation may represent a novel environmental strategy in obesity treatment.

Analysis of tourism potential for Crete island, Greece

To describe the tourism potential of an area, not only single meteorological parameters have to be taken into account, but also thermal sensation and people’s thermal comfort. The latter can be estimated by the use of human energy balance models and the derived thermal indices, which comprise all relevant meteorological parameters like air temperature, air humidity, wind speed, and short and long wave radiation fluxes. This paper makes an attempt to assess and analyze climatological parameters and the thermal comfort of Crete, its variations and trends for the period of time 1955-2001. In addition, a definition and quantification of the island’s tourism potential is carried out. Long term data from several stations are used from the existing climatic and synoptic network of Crete, including daily mean, maximum and minimum temperature, relative humidity, wind speed, and cloud cover over the whole island, in order to derive the daily Physiologically Equivalent Temperature (PET) and precipitation. In addition, possible trends of thermal comfort and precipitation on an annual and seasonal basis are analyzed. Additionally, data of the 10-minutes climatology of the Climate Research Unit of the University of Norwich have been processed in order to create high resolution (1 km) mean monthly maps for climatological parameters such as air temperature, precipitation and Physiologically Equivalent Temperature.

Differents Methods to Estimate the Mean Radiant Temperature in an Urban Canyon

The mean radiant temperature is one of the meteorological key parameters governing human energy balance and the thermal comfort of human body. This variable can be considered as the sum of all direct and reflected radiation fluxes to which the human body is exposed. After the basics of the Tmrt calculation a comparison between two methods suitable for obtaining Tmrt in a street canyon will be presented. One of the discussed methods of obtaining Tmrt is based on the utilization of a globe thermometer. The other method is the radiation environment simulation through three PC software (RayMan, ENVI-met and SOLWEIG).

O desconforto térmico estival em Lisboa - uma abordagem bioclimática

THE SUMMER THERMAL STRESS IN LISBOA; A BIOCLIMATIC APPROACH. The summer frequency of hot days was studied, in Lisboa/Portela, with daily data from the period 1981/97. We used the Physiological Equivalent Temperature, an index of thermal confort based on the human energy balance, and calculated with air temperature, vapour pressure, wind speed and mean radiant temperature. It was assumed that mean radiant temperature was equal to air temperature, which is acceptable in the shade. The days were classifiend in two groups: hot days and very hot days, according to the thresholds of PET of 29ºC and 35ºC; 10% of the days had warm stress, with a maximum of frequency in July and a great interanual variability. The relation between the thermal discomfort and the wind regime was analysed. Most of the unconfortable days had breeze conditions, with the wind blowing from the East (from the estuary) during the morning; in the afternoon, the barometric gradient between the Ocean and the Iberian Peninsula increases, the breeze is replaced by a week northerly wind. The frequent occurence of strong northerly winds in summer is an important factor of reduction of the warm stress in Lisbon

Microbiota conservation and BMI signatures in adult monozygotic twins

The human gastrointestinal (GI) tract microbiota acts like a virtual organ and is suggested to be of great importance in human energy balance and weight control. This study included 40 monozygotic (MZ) twin pairs to investigate the influence of the human genotype on GI microbiota structure as well as microbial signatures for differences in body mass index (BMI). Phylogenetic microarraying based on 16S rRNA genes demonstrated that MZ twins have more similar microbiotas compared with unrelated subjects (P<0.001), which allowed the identification of 35 genus-like microbial groups that are more conserved between MZ twins. Half of the twin pairs were selected on discordance in terms of BMI, which revealed an inverse correlation between Clostridium cluster IV diversity and BMI. Furthermore, relatives of Eubacterium ventriosum and Roseburia intestinalis were positively correlated to BMI differences, and relatives of Oscillospira guillermondii were negatively correlated to BMI differences. Lower BMI was associated with a more abundant network of primary fiber degraders, while a network of butyrate producers was more prominent in subjects with higher BMI. Combined with higher butyrate and valerate contents in the fecal matter of higher BMI subjects, the difference in microbial networks suggests a shift in fermentation patterns at the end of the colon, which could affect human energy homeostasis.

Imaging hypothalamic activity using diffusion weighted magnetic resonance imaging in the mouse and human brain

Hypothalamic appetite regulation is a vital homeostatic process underlying global energy balance in animals and humans, its disturbances resulting in feeding disorders with high morbidity and mortality. The objective evaluation of appetite remains difficult, very often restricted to indirect measurements of food intake and body weight. We report here, the direct, non-invasive visualization of hypothalamic activation by fasting using diffusion weighted magnetic resonance imaging, in the mouse brain as well as in a preliminary study in the human brain. The brain of fed or fasted mice or humans were imaged at 7 or 1.5 Tesla, respectively, by diffusion weighted magnetic resonance imaging using a complete range of b values (10<b<2000s.mm(-2)). The diffusion weighted image data sets were registered and analyzed pixel by pixel using a biexponential model of diffusion, or a model-free Linear Discriminant Analysis approach. Biexponential fittings revealed statistically significant increases in the slow diffusion parameters of the model, consistent with a neurocellular swelling response in the fasted hypothalamus. Increased resolution approaches allowed the detection of increases in the diffusion parameters within the Arcuate Nucleus, Ventromedial Nucleus and Dorsomedial Nucleus. Independently, Linear Discriminant Analysis was able to classify successfully the diffusion data sets from mice and humans between fed and fasted states. Present results are consistent with increased glutamatergic neurotransmission during orexigenic firing, a process resulting in increased ionic accumulation and concomitant osmotic neurocellular swelling. This swelling response is spatially extendable through surrounding astrocytic networks until it becomes MRI detectable. Present findings open new avenues for the direct, non-invasive, evaluation of appetite disorders and other hypothalamic pathologies helping potentially in the development of the corresponding therapies.

Urinary C‐peptide Is Not an Accurate Bioindicator of Energy Balance in Humans

The apprehension of the factors that affect long term regulation of energy balance is indispensable to understand the rise in obesity prevalence as well as to delineate levers to prevent it. Accurate measurements of energy balance are however challenging during free-living conditions. Recent studies proposed urinary C-peptide, a metabolic byproduct of insulin synthesis, as reliable noninvasive assessment of energy balance. These studies were in fact essentially based on correlations between urinary C-peptide and energy intake and only focused on nonhuman primates. During a bed-rest study conducted in 16 healthy women in a controlled environment, we tested the existence of a relationship between 24h-urinary C-peptide and energy balance in humans. Daily energy intake and body mass, body composition (dual-energy X-ray absorptiometry (DXA)) and total energy expenditure (doubly labeled water (DLW) method) was measured and energy balance was calculated as the difference between energy intake and expenditure. Urinary C-peptide was positively correlated with bed-rest-induced changes in fat mass (r(2) = 0.285; P = 0.03) and energy balance assessed at the end of the bed-rest (r(2) = 0.302; P = 0.027). However, in this tightly controlled environment, urinary C-peptide only accounted for 30% of variations in energy balance. No relationship was noted between urinary C-peptide and body or fat mass both at baseline and at the end of the bed-rest. These results indicate that urinary C-peptide cannot be used as an accurate biomarker of energy balance in the general human population in free-living conditions.

인간 열환경 지수(HumanThermal Sensation)를 이용한 조경계획 및 디자인 방법

이 연구는 인간 에너지 균형 모델에서 출발한 인간 열환경 지수 분석 방법을 이용하여 캐나다 BC주에 있는 나나이모시 상업지구안 좁은 길과 경상남도 창원시 중심상업지구에 있는 소공원을 연구 대상지로 2009년 여름철 열환경을 분석한 것이다. 기후 입력 자료는 기온, 상대습도, 풍속, 태양 및 지구 복사에너지이었으며, 그 결과 인간 열환경 지수에 가장 크게 영향을 미치는 요소들은 태양 직사광선, 건물시계지수 그리고 풍속이었다. 음지는 약간 더운 정도의 열환경을 조성하는 것으로 나타나 매우 덥게 나타난 양지에 비해 훨씬 좋은 열환경을 조성하는 것으로 나타났다. 나나이모 연구 대상지에 있는 좁은 길들은 주변의 넓은 장소들에 비해 주변 건축물에서 나오는 태양 반사광선과 지구 복사에너지들이 더 많이 영향을 미쳐 훨씬 덥게 나타났다. 낮은 풍속에 의해서 인체에서 방출되는 현열과 잠열의 양이 현저히 줄어듦으로서 더 더운 열환경이 조성되는 것으로 나타났다. 기후요소를 조경에 접목하기 위해서, 인간 열환경 지수 분석 방법을 이용하는 것은 열환경적으로 쾌적한 옥외 공간조성에 영향을 미칠 것이며, 도시 열섬 완화와 기후변화 연구에도 잘 이용될 수 있을 것이다. Human thermal sensation based on a human energy balance model was analyzed in the study areas, the Changwon and Nanaimo sites, on clear days during thesummer of 2009. The climatic input data were air temperature, relative humidity, wind speed and solar and terrestrial radiation. The most effective factors for human thermal sensation were direct beam solar radiation, building view factor and wind speed. Shaded locations had much lower thermal sensation, slightly warm, than sunny locations, very hot. Also, narrow streets in the Nanaimo site had higher thermal sensation than open spaces because of greater reflected solar radiation and terrestrial radiation from their surrounding buildings. Calm wind speed also produced much higher thermal sensation, which reduced sensible and latent heat loss from the human body. By adopting climatic factors into landscape architecture, the human thermal sensation analysis method promises to help create thermally comfortable outdoor areas. The method can also be used for urban heat island modification and climate change studies.

Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human

Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.

Endurance exercise is a leptin signaling mimetic in hypothalamus of Wistar rats

BackgroundEndurance exercise is known to promote a substantial effect on the energy balance in rats and humans. However, little is known about the exact mechanisms for the appetite-suppressive effects of endurance exercise. We hypothesized that endurance training might activate signaling cascades in the hypothalamus known to be involved in leptin signaling.Methods16 male Wistar rats were randomly assigned to two groups: sedentary (n = 8) and exercise groups (n = 8). Animals in the exercise group started treadmill running at 30 m/min, 0% grade, for 1 min/bout. Running time was gradually increased by 2 min/bout every day. The training plan was one bout per day during initial two weeks, and two bouts per day during 3rd-9th week. At the end of nine-week experiment, blood was analyzed for low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), interleukin (IL)-6, and leptin in both groups. Activations of janus kinase 2-signaling transducer and activator of transcription 3 (JAK2-STAT3), protein kinase B (Akt), extracellular regulated kninase (ERKs), and suppressor of cytokine signaling 3 (SOCS3) in hypothalamus were measured in the end of nine weeks of exercise protocol.ResultsNine-week endurance exercise induced lower concentrations of LDL-C, TG, TC, FFA, and leptin in rats (P < 0.05 or P < 0.01). Nine-week endurance exercise significantly increased the circulating IL-6 concentration compared with sedentary group (239.6 ± 37.2 pg/ml vs. 151.8 ± 31.5 pg/ml, P < 0.01). Exercise rats showed significant increases in JAK2, STAT3, Akt, ERKs, and SOCS3 phosphorylations compared with sedentary rats (P < 0.01).ConclusionThe data suggest that endurance exercise is a leptin signaling mimetic in hypothalamus of Wistar rats.

Role of the hypothalamus in the neuroendocrine regulation of body weight and composition during energy deficit

Energy deficit in lean or obese animals or humans stimulates appetite, reduces energy expenditure and possibly also decreases physical activity, thereby contributing to weight regain. Often overlooked in weight loss trials for obesity, however, is the effect of energy restriction on neuroendocrine status. Negative energy balance in lean animals and humans consistently inhibits activity of the hypothalamo-pituitary-thyroid, -gonadotropic and -somatotropic axes (or reduces circulating insulin-like growth factor-1 levels), while concomitantly activating the hypothalamo-pituitary-adrenal axis, with emerging evidence of similar changes in overweight and obese people during lifestyle interventions for weight loss. These neuroendocrine changes, which animal studies show may result in part from hypothalamic actions of orexigenic (e.g. neuropeptide Y, agouti-related peptide) and anorexigenic peptides (e.g. alpha-melanocyte-stimulating hormone, and cocaine and amphetamine-related transcript), can adversely affect body composition by promoting the accumulation of adipose tissue (particularly central adiposity) and stimulating the loss of lean body mass and bone. As such, current efforts to maximize loss of excess body fat in obese people may inadvertently be promoting long-term complications such as central obesity and associated health risks, as well as sarcopenia and osteoporosis. Future weight loss trials would benefit from assessment of the effects on body composition and key hormonal regulators of body composition using sensitive techniques.

Warm Reception? Halogenated BPA Flame Retardants and PPARγ Activation

Adverse effects highlighted in experimental studies of the industrial chemical bisphenol A (BPA) have centered on reproductive targets, but recent research suggests metabolism also may be affected. BPA is widely present in the environment, as are its halogenated derivatives. A new study investigates the structure and function of these halogenated compounds and shows they could potentially disrupt energy balance (i.e., lipid and carbohydrate homeostasis) in humans and wildlife [EHP 119(9):1227–1232; Riu et al.]. Halogenated BPA derivatives are used as flame retardants, with tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) as parent compounds. Previous studies have shown that BPA, TBBPA, and TCBPA have estrogenic activity and that BPA can alter adipogenesis (fat cell formation) in rats. Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in adipogenesis, and interference with this receptor can contribute to type 2 diabetes and obesity. Cell lines were used to test the ability of BPA, TBBPA, TCBPA, and other halogenated BPA derivatives to activate human estrogen receptors (ERα and ERβ) and human PPARs (PPARα, PPARδ, and PPARγ). The compounds also were applied to undifferentiated fat cells to test their effects on adipogenesis and the genes involved in this process. Competitive binding assays were conducted to further characterize PPARγ activation in both reporter cell lines and undifferentiated fat cells, and crystals of PPARγ bound to TBBPA and TCBPA were purified to study how the chemicals bound and activated the receptor. Another set of experiments used Xenopus and zebrafish PPARγ to test the response to BPA compounds in other species. TCBPA and lower brominated BPAs such as monoBBPA and diBBPA partially activated both ER subtypes, whereas TBBPA had little effect on either. Both TBBPA and TCBPA were able to partially activate PPARγ and promote fat cell differentiation as well as disrupt PPARγ activity in all species studied. Structural examination of the area where compounds are bound to the PPARγ receptor yielded evidence that TBBPA, TCBPA, and other halogenated BPA derivatives partially activate this receptor. What does all this mean? Essentially, the findings support the hypothesis that environmental contaminants may contribute to the disruption of energy balance in humans and wildlife. It also suggests that halogenated derivatives of BPA used as flame retardants, which have not been extensively studied to date, may contribute to obesity. The main active form of PPARγ is the retinoid X receptor (RXR)/PPARγ heterodimer. According to the authors, environmental exposure to BPA compounds alongside other endocrine disruptors with similar RXR and/or PPARγ activity sets the stage for additive and synergistic effects, potentially leading to increased risk of metabolic disease.

Bath Breakfast Project (BBP)--examining the role of extended daily fasting in human energy balance and associated health outcomes: study protocol for a randomised controlled trial [ISRCTN31521726

BackgroundCurrent guidance regarding the role of daily breakfast in human health is largely grounded in cross-sectional observations. However, the causal nature of these relationships has not been fully explored and what limited information is emerging from controlled laboratory-based experiments appears inconsistent with much existing data. Further progress in our understanding therefore requires a direct examination of how daily breakfast impacts human health under free-living conditions.Methods/DesignThe Bath Breakfast Project (BBP) is a randomised controlled trial comparing the effects of daily breakfast consumption relative to extended fasting on energy balance and human health. Approximately 70 men and women will undergo extensive laboratory-based assessments of their acute metabolic responses under fasted and post-prandial conditions, to include: resting metabolic rate, substrate oxidation, dietary-induced thermogenesis and systemic concentrations of key metabolites/hormones. Physiological and psychological indices of appetite will also be monitored both over the first few hours of the day (i.e. whether fed or fasted) and also following a standardised test lunch used to assess voluntary energy intake under controlled conditions. Baseline measurements of participants' anthropometric characteristics (e.g. DEXA) will be recorded prior to intervention, along with an oral glucose tolerance test and acquisition of adipose tissue samples to determine expression of key genes and estimates of tissue-specific insulin action. Participants will then be randomly assigned either to a group prescribed an energy intake of ≥3000 kJ before 1100 each day or a group to extend their overnight fast by abstaining from ingestion of energy-providing nutrients until 1200 each day, with all laboratory-based measurements followed-up 6 weeks later. Free-living assessments of energy intake (via direct weighed food diaries) and energy expenditure (via combined heart-rate/accelerometry) will be made during the first and last week of intervention, with continuous glucose monitors worn both to document chronic glycaemic responses to the intervention and to verify compliance.Trial registrationCurrent Controlled Trials ISRCTN31521726.

Calcium and obesity: effect size and clinical relevance

The connection between calcium intake and body weight was first described by McCarron et al.,1 who found an inverse relationship between these two variables in the National Health and Nutrition Examination Survey (NHANES) data. This observation was largely ignored for the next 16 years, until Zemel et al.2 described the weight-loss effect of calcium supplementation in a hypertension trial and suggested a cell biologic basis for the action of calcium in adipocytes. Since that time, there have been well over 100 reports of both experimental and observational studies evaluating the role of calcium intake in energy balance and body composition in humans. As summarized in 2009 in this journal,3 most of these studies found that increased calcium intake augmented the weight loss of energy-restricted diets, protected lean body mass, and reduced age-related weight gain, or that it had null effect. A very few reported negative findings (i.e., high calcium intakes were associated with weight gain), but the preponderance of the evidence tilted clearly toward the side of calcium intake favoring weight loss. In the present issue of this journal, Onakpoya et al.4 present yet another meta-analysis of this topic, with the results also favoring calcium. They report a highly significant, positive effect of calcium supplementation on total body weight loss and a somewhat larger effect on fat loss (suggesting some protection of lean tissue mass, which is a frequent casualty … [↵][1] RP Heaney , Creighton University, 2500 California Plaza, Omaha, NE 68178, USA. E-mail: rheaney{at}creighton.edu [1]: #xref-corresp-1-1