Appetite and energy balancing

AbstractThe idea that food intake is motivated by (or in anticipation of) ‘hunger’ arising from energy depletion is apparent in both public and scientific discourse on eating behaviour. In contrast, our thesis is that eating is largely unrelated to short-term energy depletion. Energy requirements meal-to-meal are trivial compared with total body energy stores, and energy supply to the body's tissues is maintained if a meal or even several meals are missed. Complex and exquisite metabolic machinery ensures that this happens, but metabolic regulation is only loosely coupled with the control of energy intake. Instead, food intake needs to be controlled because the limited capacity of the gut means that processing a meal presents a significant physiological challenge and potentially hinders other activities. We illustrate the relationship between energy (food) intake and energy expenditure with a simple analogy in which: (1) water in a bathtub represents body energy content, (2) water in a saucepan represents food in the gut, and (3) the bathtub is filled via the saucepan. Furthermore, (4) it takes hours to process and pass the full energy (macronutrient) content of the saucepan to the bathtub, and (5) both the saucepan and bathtub resist filling, representing negative feedbacks on appetite (desire to eat). This model is consistent with the observations that appetite is reduced acutely by energy intake (a meal added to the limited capacity of the saucepan/gut), but not increased by an acute increase in energy expenditure (energy removed from the large store of energy in the bathtub/body). The existence of relatively very weak but chronic negative feedback on appetite proportional to body fatness is supported by observations on the dynamics of energy intake and weight gain in rat dietary obesity. (We use the term ‘appetite’ here because ‘hunger’ implies energy depletion.) In our model, appetite is motivated by the accessibility of food and the anticipated and experienced pleasure of eating it. The latter, which is similar to food reward, is determined primarily by the state of emptiness of the gut and food liking related to the food's sensory qualities and macronutrient value and the individual's dietary history. Importantly, energy density adds value because energy dense foods are less satiating kJ for kJ and satiation limits further intake. That is, energy dense foods promote energy intake by virtue (1) of being more attractive and (2) having low satiating capacity kJ for kJ, and (1) is partly a consequence of (2). Energy storage is adapted to feast and famine and that includes unevenness over time of the costs of obtaining and ingesting food compared with engaging in other activities. However, in very low-cost food environments with energy dense foods readily available, risk of obesity is high. This risk can be and is mitigated by dietary restraint, which in its simplest form could mean missing the occasional meal. Another strategy we discuss is the energy dilution achieved by replacing some sugar in the diet with low-calorie sweeteners. Perhaps as or more significant, though, is that belief in short-term energy balancing (the energy depletion model) may undermine attempts to eat less. Therefore, correcting narratives of eating to be consistent with biological reality could also assist with weight control

Old and New Fields on Super Riemann Surfaces

The ``new fields" or ``superconformal functions" on $N=1$ super Riemann surfaces introduced recently by Rogers and Langer are shown to coincide with the Abelian differentials (plus constants), viewed as a subset of the functions on the associated $N=2$ super Riemann surface. We confirm that, as originally defined, they do not form a super vector space.Comment: 9 pages, LaTex. Published version: minor changes for clarity, two new reference

Vortices and the entrainment transition in the 2D Kuramoto model

We study synchronization in the two-dimensional lattice of coupled phase oscillators with random intrinsic frequencies. When the coupling $K$ is larger than a threshold $K_E$, there is a macroscopic cluster of frequency-synchronized oscillators. We explain why the macroscopic cluster disappears at $K_E$. We view the system in terms of vortices, since cluster boundaries are delineated by the motion of these topological defects. In the entrained phase ($K>K_E$), vortices move in fixed paths around clusters, while in the unentrained phase ($K<K_E$), vortices sometimes wander off. These deviant vortices are responsible for the disappearance of the macroscopic cluster. The regularity of vortex motion is determined by whether clusters behave as single effective oscillators. The unentrained phase is also characterized by time-dependent cluster structure and the presence of chaos. Thus, the entrainment transition is actually an order-chaos transition. We present an analytical argument for the scaling $K_E\sim K_L$ for small lattices, where $K_L$ is the threshold for phase-locking. By also deriving the scaling $K_L\sim\log N$, we thus show that $K_E\sim\log N$ for small $N$, in agreement with numerics. In addition, we show how to use the linearized model to predict where vortices are generated.Comment: 11 pages, 8 figure

Structural and Functional Evaluation of Clinically Relevant Inhibitors of Steroidogenic Cytochrome P450 17A1

Human steroidogenic cytochrome P450 17A1 (CYP17A1) is a bifunctional enzyme that performs both hydroxylation and lyase reactions, with the latter required to generate androgens that fuel prostate cancer proliferation. The steroid abiraterone, the active form of the only CYP17A1 inhibitor approved by the Food and Drug Administration, binds the catalytic heme iron, nonselectively impeding both reactions and ultimately causing undesirable corticosteroid imbalance. Some nonsteroidal inhibitors reportedly inhibit the lyase reaction more than the preceding hydroxylase reaction, which would be clinically advantageous, but the mechanism is not understood. Thus, the nonsteroidal inhibitors seviteronel and orteronel and the steroidal inhibitors abiraterone and galeterone were compared with respect to their binding modes and hydroxylase versus lyase inhibition. Binding studies and X-ray structures of CYP17A1 with nonsteroidal inhibitors reveal coordination to the heme iron like the steroidal inhibitors. (S)-seviteronel binds similarly to both observed CYP17A1 conformations. However, (S)-orteronel and (R)-orteronel bind to distinct CYP17A1 conformations that differ in a region implicated in ligand entry/exit and the presence of a peripheral ligand. To reconcile these binding modes with enzyme function, side-by-side enzymatic analysis was undertaken and revealed that neither the nonsteroidal seviteronel nor the (S)-orteronel inhibitors demonstrated significant lyase selectivity, but the less potent (R)-orteronel was 8- to 11-fold selective for lyase inhibition. While active-site iron coordination is consistent with competitive inhibition, conformational selection for binding of some inhibitors and the differential presence of a peripheral ligand molecule suggest the possibility of CYP17A1 functional modulation by features outside the active site

Predicting functional outcomes after stroke: An observational study of acute single-channel EEG

Background: Early and objective prediction of functional outcome after stroke is an important issue in rehabilitation. Electroencephalography (EEG) has long been utilized to describe and monitor brain function following neuro-trauma, and technological advances have improved usability in the acute setting. However, skepticism persists whether EEG can provide the same prognostic value as neurological examination. Objective: The current cohort study examined the relationship between acute single-channel EEG and functional outcomes after stroke. Methods: Resting-state EEG recorded at a single left pre-frontal EEG channel (FP1) was obtained from 16 adults within 72 h of first stroke. At 30 and 90 days, measures of disability (modified Rankin Scale; mRS) and involvement in daily activities (modified Barthel Index; mBI) were obtained. Acute EEG measures were correlated with functional outcomes and compared to an early neurological examination of stroke severity using the National Institute of Health Stroke Scale (NIHSS). Classification of good outcomes (mRS ≤1 or mBI ≥95) was also examined using Receiver Operator Curve analyses. Results: One-third to one-half of participants experienced incomplete post-stroke recovery, depending on the time point and measure. Functional outcomes correlated with acute theta values (rs 0.45–0.60), with the strength of associations equivalent to previously reported values obtained from conventional multi-channel systems. Acute theta values ≥0.25 were associated with good outcomes, with positive (67-83%) and negative predictive values (70-90%) comparable to those obtained using the NIHSS. Conclusions: Acute, single-channel EEG can provide unique, non-overlapping clinical information, which may facilitate objective prediction of functional outcome after stroke

Universality in the one-dimensional chain of phase-coupled oscillators

We apply a recently developed renormalization group (RG) method to study synchronization in a one-dimensional chain of phase-coupled oscillators in the regime of weak randomness. The RG predicts how oscillators with randomly distributed frequencies and couplings form frequency-synchronized clusters. Although the RG was originally intended for strong randomness, i.e. for distributions with long tails, we find good agreement with numerical simulations even in the regime of weak randomness. We use the RG flow to derive how the correlation length scales with the width of the coupling distribution in the limit of large coupling. This leads to the identification of a universality class of distributions with the same critical exponent $\nu$. We also find universal scaling for small coupling. Finally, we show that the RG flow is characterized by a universal approach to the unsynchronized fixed point, which provides physical insight into low-frequency clusters.Comment: 14 pages, 10 figure

Portion Size Influences Intake in Samburu Kenyan People Not Exposed to the Western Obesogenic Environment

For people in the modernized food environment, external factors like food variety, palatability, and ubiquitous learned cues for food availability can overcome internal, homeostatic signals to promote excess intake. Portion size is one such external cue; people typically consume more when served more, often without awareness. Though susceptibility to external cues may be attributed to the modernized, cue-saturated environment, there is little research on people living outside that context, or with distinctly different food norms. We studied a sample of Samburu people in rural Kenya who maintain a traditional, semi-nomadic pastoralist lifestyle, eat a very limited diet, and face chronic food insecurity. Participants (12 male, 12 female, aged 20–74, mean BMI = 18.4) attended the study on two days and were provided in counterbalanced order an individual serving bowl containing 1.4 or 2.3 kg of a familiar bean and maize stew. Amount consumed was recorded along with post-meal questions in their dialect about their awareness of intake amount. Data were omitted from two participants who consumed the entire portion in a session. Even though the ‘smaller’ serving was a very large meal, participants consumed 40% more when given the larger serving, despite being unable to reliably identify which day they consumed more food. This result in the Samburu demonstrates the portion size effect is not a by-product of the modern food environment and may represent a more fundamental feature of human dietary psychology

Individual variability in preference for energy-dense foods fails to predict child BMI percentile

Many studies show that higher dietary energy density is associated with greater body weight. Here we explored two propositions: i) that child BMI percentile is associated with individual differences in children's relative preference for energy-dense foods, ii) that child BMI percentile is associated with the same individual differences between their parents. Child-parent dyads were recruited from a local interactive science center in Bristol (UK). Using computerized tasks, participants ranked their preference and rated their liking for a range of snack foods that varied in energy density. Children (aged 3–14 years, N = 110) and parents completed the tasks for themselves. Parents also completed two further tasks in which they ranked the foods in the order that they would prioritize for their child, and again, in the order that they thought their child would choose. Children preferred (t(109) = 3.91, p ≺ 0.001) and better liked the taste of (t(109) = 3.28, p = 0.001) higher energy-dense foods, and parents correctly estimated this outcome (t(109) = 7.18, p ≺ 0.001). Conversely, lower energy-dense foods were preferred (t(109) = − 4.63, p ≺ 0.001), better liked (t(109) = − 2.75, p = 0.007) and served (t(109) = − 15.06, p ≺ 0.001) by parents. However, we found no evidence that child BMI percentile was associated with child or parent preference for, or liking of, energy-dense foods. Therefore, we suggest that the observed relationship between dietary energy density and body weight is not explained by individual differences in preference for energy density

Energy-dense snacks can have the same expected satiation as sugar-containing beverages

AbstractSugar-sweetened beverages (SSBs) are thought to be problematic for weight management because energy delivered in liquid form may be less effective at suppressing appetite than solid foods. However, little is known about the relative ‘expected satiation’ (anticipated fullness) of SSBs and solid foods. This is relevant because expected satiation is an important determinant of portion selection and energy intake. Here, we used a method of constant stimuli to assess the expected satiation of test meals that were presented in combination with different caloric and non-caloric beverages (500 ml) (Experiment 1 and 2), as well as with high-energy solid snack foods (Experiment 2). All energy-containing beverages and snack foods were presented in 210 kcal portions. Both experiments found that expected satiation was greater for meals containing caloric versus non-caloric beverages (201.3 ± 17.3 vs. 185.4 ± 14.1 kcal in Experiment 2; p < 0.05). Further, Experiment 2 showed that this difference was greater in participants who were familiar with our test beverages, indicating a role for learning. Notably, we failed to observe a significant difference in expected satiation between any of the caloric beverages and snack foods in Experiment 2 (range: 192.5–205.2 kcal; p = 0.87). This finding suggests that it may be more appropriate to consider beverages and solid foods on the same continuum, recognizing that the expected satiation of some solid foods is as weak as some beverages