R. James Stubbs

Plasma concentrations of alpha-MSH, AgRP and leptin in lean and obese men and their relationship to differing states of energy balance perturbation

objective  A great deal of attention has focused on the central role of alpha melanocyte‐stimulating hormone (α‐MSH) and its antagonism at the melanocortin‐4 receptor (MC4R) by agouti related protein (AgRP) in the regulation of energy balance. However, very little is known regarding the function of circulating AgRP and α‐MSH in humans. We aimed to determine whether circulating α‐MSH and AgRP are responsive to long‐term perturbations in energy balance, in a manner consistent with their central putative functions.

APPETITE, FEEDING BEHAVIOUR AND ENERGY BALANCE IN HUMAN SUBJECTS

Since the Second World War there has been a secular trend of increased overweight and obesity in societies where people have ad libitum access to Westem-type diets (Royal College of Physicians, 1983; Gregory et al. 1990; White et al. 1991; Department of Health, 1995). Over this time period the economic costs of obesity and the personal costs of being overweight (in terms of reduced quality of life, increased morbidity and mortality) have been well documented (Seidell, 1995). Throughout this period scientific efforts have intensified in attempting to understand the cause of overweight and obesity and in endeavours to produce effective approaches to sustained body-weight reduction. Ironically, the increased governmental, public health and biomedical research efforts aimed at understanding how to reverse current secular trends in body fatness have been accompanied by an escalation of those very trends. We have now reached the remarkable situation in the UK whereby more that half of the adult population has been categorized as collectively overweight and obese (Department of Health, 1995). By considering research trends in the area of human energy balance (EB) over the last two decades it should become apparent that current research has grown out of and built on the research that went before it. Several of the hypotheses of the 1970s and 1980s have been rejected as inoperable in human subjects in the light of the evidence that was collected to evaluate them. It is worth remembering that disproving an hypothesis does not reduce the contribution it has made to scientific understanding. The very process of disproving the hypothesis actually advances science and leads to new avenues of investigation. It is unfortunate that the meticulous process of hypothesis-testing necessarily proceeds at a somewhat slower rate than the problem that we are trying to address: a large prevalence of excess body weight. However, considerable progress has been made over the last two decades in understanding the major factors most likely to alter EB in man and the types of model which are likely to explain how some people become overweight and obese. These insights have proved invaluable in helping us address current issues pertinent to the control of EB and in targeting key research areas for the future. In order to fully illustrate this point it is worth considering the direction of research into obesity and EB over the last couple of decades.

Effects of two weeks' mandatory snack consumption on energy intake and energy balance.

Objective: Our goal was to compare the effects of mandatory consumption of commercial snack products (CSPs) on energy intakes and energy balance in free‐living adults and to assess the interaction between habitual level of CSP consumption and the interventions.

Weight outcomes audit for 34,271 adults referred to a primary care/commercial weight management partnership scheme

Objective: This project audited rate and extent of weight loss in a primary care/commercial weight management organisation partnership scheme. Methods: 34,271 patients were referred to Slimming World for 12 weekly sessions. Data were analysed using individual weekly weight records. Results: Average (SD) BMI change was –1.5 kg/m2 (1.3), weight change –4.0 kg (3.7), percent weight change –4.0% (3.6), rate of weight change –0.3 kg/week, and number of sessions attended 8.9 (3.6) of 12. For patients attending at least 10 of 12 sessions (n = 19,907 or 58.1%), average (SD) BMI change was –2.0 kg/m2 (1.3), weight change –5.5 kg (3.8), percent weight change –5.5% (3.5), rate of weight change –0.4 kg/week, and average number of sessions attended was 11.5 (0.7) (p < 0.001, compared to all patients). Weight loss was greater in men (n = 3,651) than in women (n = 30,620) (p < 0.001). 35.8% of all patients enrolled and 54.7% in patients attending 10 or more sessions achieved at least 5% weight loss. Weight gain was prevented in 92.1% of all patients referred. Attendance explained 29.6% and percent weight lost in week 1 explained 18.4% of the variance in weight loss. Conclusions: Referral to a commercial organisation is a practical option for National Health Service (NHS) weight management strategies, which achieves clinically safe and effective weight loss.

Carbohydrates and Energy Balance

In the early 1970s carbohydrates (CHOs) were believed to induce overconsumption and excess fat deposition. They are now perceived to protect against these consequences. This paper evaluates the evidence for this change of interpretation by considering (1) the energy content of CHOs, (2) the energetic efficiency with which they are handled by the body, and (3) their effects on appetite, relative to other macronutrients. CHOs are the least energy-dense macronutrients (delta Hc) and exhibit the greatest variability in digestibility. Doubling the usual levels of nonstarch polysaccharides (fiber) may decrease digestibility of a Western diet by 5%. De novo lipogenesis from dietary CHO is energetically inefficient but very limited on Western diets, which are relatively high in fat. There appears to be a hierarchy (protein > CHO > fat) in the extent to which the stores of the macronutrients are autoregulated by oxidation. Excess CHO intake tends to promote storage (but not de novo synthesis) of fat. The thermogenic effects of CHO are therefore relatively limited on Western diets. Per MJ of energy ingested, macronutrients differentially affect satiety (protein > CHO > fat) under conditions where fat is disproportionately energy dense. Isoenergetically dense loads of fat and CHO exert less pronounced differences on satiety. Under some conditions HC diets promote excess energy intakes. There is little evidence that a CHO-rich diet, or one with intense sweeteners, promotes spontaneous weight loss.

Effects of added fruits and vegetables on dietary intakes and body weight in Scottish adults

An increased consumption of fruits and vegetables (F&V) has been suggested as a way to limit, or even lower, energy and fat intakes. The present study examined the effects of incorporating F&V supplements into the diets of adults who reported consuming <240 g (three portions) of F&V per d on energy and fat intakes, and change in body weight, over 8 weeks using a randomised parallel design. Thirty-four males and twenty-eight females (age 42.6 (sd 11.1) years, BMI 23.7 (sd 2.7) kg/m(2)) were each provided with supplements of 0, 300 or 600 g F&V per d. Food, nutrient and energy intakes were measured before, during and at the end of the supplementation period using 7 d weighed records. Mean daily energy intakes were not different among the three groups before (P = 0.151) or during the supplementation periods (P = 0.407), although changes in energy intakes over the study period tended to be more positive with increasing amounts of F&V supplements (P = 0.078). There was no difference in changes of body weights during the study (P = 0.242). Carbohydrate (P < 0.001), sugar (P < 0.001), fibre (P < 0.001) and weight of food consumed (P = 0.022) increased in the treatment groups. There were no significant differences, or changes, in fat intakes among the three groups. Consumption of mandatory F&V supplements for 8 weeks produced beneficial changes in diet composition, but did not result in lower reported energy or fat intakes, and did not result in loss of body weight.

Description and evaluation of a Newton-based electronic appetite rating system for temporal tracking of appetite in human subjects.

This study assessed the reliability and validity of a palm-top-based electronic appetite rating system (EARS) in relation to the traditional paper and pen method. Twenty healthy subjects [10 male (M) and 10 female (F)] - mean age M=31 years (S.D.=8), F=27 years (S.D.=5); mean BMI M=24 (S.D.=2), F=21 (S.D.=5) - participated in a 4-day protocol. Measurements were made on days 1 and 4. Subjects were given paper and an EARS to log hourly subjective motivation to eat during waking hours. Food intake and meal times were fixed. Subjects were given a maintenance diet (comprising 40% fat, 47% carbohydrate and 13% protein by energy) calculated at 1.6xResting Metabolic Rate (RMR), as three isoenergetic meals. Bland and Altmans test for bias between two measurement techniques found significant differences between EARS and paper and pen for two of eight responses (hunger and fullness). Regression analysis confirmed that there were no day, sex or order effects between ratings obtained using either technique. For 15 subjects, there was no significant difference between results, with a linear relationship between the two methods that explained most of the variance (r(2) ranged from 62.6 to 98.6). The slope for all subjects was less than 1, which was partly explained by a tendency for bias at the extreme end of results on the EARS technique. These data suggest that the EARS is a useful and reliable technique for real-time data collection in appetite research but that it should not be used interchangeably with paper and pen techniques.

An evaluation of the IDEEA activity monitor for estimating energy expenditure

Objective estimates of activity patterns and energy expenditure (EE) are important for the measurement of energy balance. The Intelligent Device for Energy Expenditure and Activity (IDEEA) can estimate EE from the thirty-five postures and activities it can identify and record. The present study evaluated the IDEEA systems estimation of EE using whole-body indirect calorimetry over 24 h, and in free-living subjects using doubly-labelled water (DLW) over 14 d. EE was calculated from the IDEEA data using calibration values for RMR and EE while sitting and standing, both as estimated by the IDEEA system (IDEEA(est)) and measured by indirect calorimetry (IDEEA(meas)). Subjects were seven females and seven males, mean age 38·1 and 39·7 years, mean BMI 25·2 and 26·2 kg/m2, respectively. The IDEEA(est) method produced a similar estimate of EE to the calorimeter (10·8 and 10·8 MJ, NS), while the IDEEA(meas) method underestimated EE (9·9 MJ, P < 0·001). After removing data from static cycling, which the IDEEA was unable to identify as an activity, both the IDEEA(est) and IDEEA(meas) methods overestimated EE compared to the calorimeter (9·9 MJ, P < 0·001; 9·1 MJ, P < 0·05 and 8·6 MJ, respectively). Similarly, the IDEEA system overestimated EE compared to DLW over 14 d; 12·7 MJ/d (P < 0·01), 11·5 MJ/d (P < 0·01) and 9·5 MJ/d for the IDEEA(est), IDEEA(meas) and DLW, respectively. The IDEEA system overestimated EE both in the controlled laboratory and free-living environments. Using measured EE values for RMR, sitting and standing reduced, but did not eliminate, the error in estimated EE.

Effect of flavour of liquid Ensure diet supplement on energy intake in male SD rats.

Outbred male Sprague-Dawley rats were provided with one of the four flavours of the liquid diet, Ensure, in addition to chow pellets, to examine whether differences in flavour lead to differences in energy intake i.e. degree of over-consumption. For half the rats, the Ensure supplement was provided for 14 days and then withdrawn for the final 8 days of the study, whereas the remaining animals were allowed to consume Ensure for 22 days. All four flavours of Ensure, chocolate, vanilla, coffee and asparagus, induced a sustained increase in daily energy intake of approximately 15%. There was an effect of flavour on initial consumption of the Ensure diet, with coffee and asparagus flavours being consumed less avidly than vanilla or chocolate. However, this effect was short-lived. Overall, there was no effect of flavour on body weight gain, energy intake from Ensure, total energy intake, body composition, or measured blood hormones and metabolites. Withdrawal of Ensure resulted in reductions in body weight gain, total energy intake, fat but not lean tissue mass, and concentrations of blood leptin, non-esterified fatty acids and triglycerides, but there was no effect of the flavour of Ensure previously supplied on any of these parameters. The ability of the liquid diet, Ensure, to stimulate long-term caloric over-consumption is not due to its flavouring. Rather, other attributes of Ensure must be more important, such as its intrinsic flavour, liquid formulation, macronutrient composition, and ease of ingestion, digestion and absorption.

Interrelationship Between Circulating Leptin Concentrations, Hunger, and Energy Intake in Healthy Subjects Receiving Tube Feeding

BACKGROUND Tube feeding is an unphysiological route of nutrient delivery, and yet there is a lack of controlled trials examining its effects on appetite, food intake, and factors involved in their control. This study aimed to investigate the relationship between diurnal tube feeding, hunger, food intake, and circulating concentrations of leptin (a putative satiety factor). METHODS Six healthy lean men received a continuous nasogastric infusion (9:00 AM to 9:00 PM) of colored water (2 days), liquid feeding (4.2 kJ/mL, energy provision 1 x the initial predicted basal metabolic rate; 3 days), and colored water (2 days). Measurements of hunger (visual analog scales), weighed food intake, and fasting circulating leptin concentrations were made while the subjects were allowed free access to isoenergetically dense food items. RESULTS Three days of diurnal nasogastric feeding (mean, 6.9 MJ/d) significantly increased total energy intake (to 19.4 MJ/d; p < .001; analysis of variance [ANOVA]), suppressing oral energy intake by only 17%, with no significant effect on mean daily hunger. Higher levels of energy intake led to a universal rise in circulating leptin concentrations (2.82 to 4.23 ng/mL; p < .004; ANOVA) that was not significantly related to subsequent breakfast energy intake, first rated hunger of the day, timing of morning food consumption, or subsequent mean daily oral energy intake or hunger. CONCLUSIONS This study suggests that 3 days of diurnal tube feeding (equivalent to basal metabolic rate) failed to suppress hunger and reduced food intake by only 17%. The rise in circulating leptin concentrations, associated with tube feeding and the increase in total energy intake, failed to predict subsequent hunger or oral energy intake.