Biomedical subjects

R James Stubbs

Publications and source records attributed to R James Stubbs.

7 recordsLinked to original sources

PubMed2004

A decrease in physical activity affects appetite, energy, and nutrient balance in lean men feeding ad libitum.

BACKGROUND: It is not clear how decreased activity quantitatively affects energy balance (EB) in subjects feeding ad libitum. OBJECTIVE: We assessed the effect of an imposed sedentary routine on appetite, energy intake (EI), EB, and nutrient balance in lean men for 7 d. DESIGN: Six men with a mean (+/-SD) age of 23.0 +/- 2.3 y, weight of 69.2 +/- 11.4 kg, and height of 1.76 +/- 0.07 m were each studied twice during a sedentary [1.4 x resting metabolic rate (RMR)] and a moderately active (1.8 x RMR) regimen. During each treatment, they resided in the whole-body indirect calorimeter for the 7 d and had ad libitum access to a medium-fat diet of constant, measurable composition. Meal size, frequency, and composition were continually monitored. Motivation to eat was recorded during waking hours. Subjects were weighed in light clothing each morning, and their weight was corrected to nude. RESULTS: Energy expenditure was 9.7 and 12.8 MJ/d [P < 0.01; SE of the difference between means (SED) = 0.41] during the sedentary and active regimens, respectively. EI was 13.5 and 14.4 MJ/d (P = 0.463, SED = 1.06), respectively. There was no regimen effect on hunger, appetite, or body weight. By day 7, cumulative EB was 26.3 and 11.1 MJ, respectively. CONCLUSIONS: Reducing a level of physical activity from 1.8 to 1.4 x RMR can markedly affect EB. A sedentary routine does not induce a compensatory reduction of EI and leads to a significantly positive EB, most of which is stored as fat.

Adult↗

PubMed2004

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 (alpha-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 alpha-MSH in humans. We aimed to determine whether circulating alpha-MSH and AgRP are responsive to long-term perturbations in energy balance, in a manner consistent with their central putative functions. DESIGN AND MEASUREMENTS: Circulating alpha-MSH, AgRP and leptin were measured in both lean (n = 11) and obese (n = 18) male volunteers, some of whom (lean n = 11, obese n = 12) were then allocated one of two weight-loss dietary strategies to achieve about 5% weight loss. This was achieved by either total starvation (for 4-6 days) for rapid weight loss or a very low calorie diet (VLCD, 2.6 MJ/day) (11-12 days) for less rapid weight loss, in both the lean and obese volunteers. RESULTS: At baseline, prior to any weight loss both plasma alpha-MSH (15.8 +/- 1.2 vs. 5.8 +/- 1.0 pmol/l +/- SEM; P < 0.001) and AgRP (49.4 +/- 2.4 vs. 10.1 +/- 0.9 pg/ml +/- SEM; P < 0.001) were elevated in obese subjects compared with lean. In both cases this correlated closely with fat mass (P < 0.001), percentage body fat (P < 0.001) and leptin (P < 0.05). Plasma AgRP increased significantly during a 6-day fast in lean individuals (11.1 +/- 1.6 vs. 21.6 +/- 3.1 pg/ml +/- SEM; P < 0.05) but not in the VLCD subjects or in the obese, while alpha-MSH was not affected by any changes in energy balance in either the lean or the obese volunteers. CONCLUSION: We show a difference in alpha-MSH and AgRP in lean and obese subjects that correlates closely with body fat at baseline. We demonstrate an increase in plasma AgRP during a 6-day fast in lean individuals that is coincident with a decrease in plasma leptin. This increase in AgRP was not due to weight loss per se as there was no change in AgRP as a result of the same weight loss in the VLCD intervention in lean individuals. The source of the increase in plasma AgRP and its physiological function in the periphery remains to be elucidated but we suggest that the dynamics of the change in plasma leptin may determine the elevation in fasting plasma AgRP in lean subjects.

Adult↗

PubMed2004

Influence of short-term dietary weight loss on cortisol secretion and metabolism in obese men.

OBJECTIVES: Obesity is associated with increased inactivation of cortisol by hepatic A-ring 5alpha- and 5beta-reductases, impaired hepatic regeneration of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), but increased subcutaneous adipose 11HSD1 activity enhancing local cortisol levels in fat. Cause and effect between obesity and abnormal cortisol metabolism is untested. DESIGN: Acute weight loss was induced by very low calorie diet (VLCD) or starvation in obese men. METHODS: Otherwise healthy males (aged 20-55 years; body mass index (BMI) 30-40 kg/m2) were studied after 6 days on a weight maintenance diet; then after either 6 days of starvation (n=6) or 3 weeks of VLCD (2.55 MJ; n=6); then after 1 week of weight maintenance; and finally after 2 weeks of being allowed to feed ad libitum. Plasma samples were obtained from indwelling cannulae at 0930 h and 1815 h and a 24 h urine collection was completed for analysis of cortisol metabolites by gas chromatography/mass spectrometry. RESULTS: Data are mean+/-S.E.M. BMI fell (kg/m3) from 34.8+/-0.8 at baseline to 31.8+/-1.4 on VLCD and 32.7+/-1.1 on starvation. Starvation caused a rise in plasma cortisol (at 0930 h from 143+/-17 to 216+/-11 nM, P<0.001) but no change in total urinary cortisol metabolites. VLCD did not alter plasma cortisol and markedly reduced cortisol metabolite excretion (from 15.8+/-1.1 mg/day at baseline to 7.0+/-1.1 mg/day, P<0.001). Relative excretion of 5alpha-reduced cortisol metabolites fell on both diets, but there were no changes in cortisol/cortisone metabolite ratios reflecting 11HSD activities. CONCLUSIONS: Weight loss with VLCD in obesity reverses up-regulation of hepatic A-ring reductases and normalises cortisol production rate; in contrast, starvation produces acute stress and further activation of cortisol secretion. We suggest that activation of cortisol secretion is not an irreversible intrinsic abnormality in obese patients, and speculate that dietary content has an important influence on the neuroendocrine response to weight loss.

Adult↗

PubMed2003

The effect of rate and extent of weight loss on urea salvage in obese male subjects.

It is well established that in human subjects a proportion of urea production undergoes hydrolysis in the gastrointestinal tract with release of N potentially available for amino acid synthesis. Previous studies have suggested adaptive changes in urea kinetics, with more urea-N retained within the metabolic pool during reduced dietary intakes of energy and protein. We therefore investigated the effect of rate and extent of weight loss on adaptive changes in urea kinetics in two groups (each n 6) of obese men (mean age 43 (sd 12) years, BMI 34.8 (sd 2.9) kg/m(2)) during either total starvation for 6 d or a very-low-energy diet (2.55 MJ/d) for 21 d. Subjects were resident in the Human Nutrition Unit of the Rowett Research Institute (Aberdeen, Scotland, UK) and lost 6 and 9 % initial body weight within the starvation and dieting groups respectively. Changes in urea-N metabolism were assessed by stable isotope tracer kinetics using [(15)N(15)N]urea infused intravenously for 36 h before, during and after weight loss. In response to weight loss, urea production decreased (P<0.01) by 25 % from 278 to 206 micromol urea-N/h per kg within the dieting group only. However, no changes were observed in the proportion of urea being hydrolysed in the gastrointestinal tract (range 20-25 %) or in the proportion of N retained for anabolic purposes (80-85 % urea-N from gastrointestinal hydrolysis) within either group. It was concluded that no adaptive changes in urea kinetics occurred in response to either the different rate or extent of weight loss.

Adaptation, Physiological↗

PubMed2003

Short-term continuous enteral tube feeding schedules did not suppress appetite and food intake in healthy men in a placebo-controlled trial.

Tube feeding (TF) provides a model with which to study appetite when nutrient delivery bypasses the upper gastrointestinal (GI) tract and associated cephalic phase response. Nocturnal, diurnal and 24-h TF schedules are used clinically, but their effects on satiety have not been distinguished. This study tested two hypotheses: 1) bypassing the upper GI tract with TF has little satiating effect, and 2) diurnal TF suppresses appetite and food intake more than nocturnal or 24-h schedules. Six healthy men, residing in a metabolic suite, each received three continuous TF schedules (diurnal 12-h, nocturnal 12-h and 24-h; 6.86 +/- 0.51 MJ/d) in random order for 3 d over separate 10-d periods. Two days before and after TF, a placebo feed (<0.4 MJ/d) was given. Weighed measurements of ad libitum food consumption, hourly tracking of appetite and metabolic and hormonal measurements were undertaken. Compared with placebo feeding, there was a nonsignificant reduction in oral intake (1.01-2.49 MJ reduction), little change in appetite sensations with TF and an increase in total energy intake from 14.88 to 20.42 +/- 3.25 MJ. The schedules did not differ although diurnal TF was the most satiating. Changes in a variety of mediators (including leptin, insulin, cholecystokinin, metabolites and respiratory quotient) did not relate to immediate assessments of appetite and food intake. This trial suggests that continuous TF has little effect on satiety in healthy men over a period of 3 d, irrespective of the timing of the schedule. This could not be explained by changes in a variety of metabolic and hormonal signals within the time frame studied.

Appetite↗

PubMed2002

The effect of rate of weight loss on erythrocyte glutathione concentration and synthesis in healthy obese men.

Obesity is commonly associated with a high incidence and prevalence of dyslipidaemia, cardiovascular disease and Type II diabetes. Interestingly, studies have also reported decreased antioxidant levels in obese subjects. This may constitute an independent risk factor in the pathogenesis of coronary artery disease as obese subjects would have a decreased capacity to prevent the oxidative modification of low-density lipoproteins, which is a mechanism suggested as central to the development of atherogenesis. As part of a study to investigate responses to weight loss, we have assessed the effects on GSH status of a decrease in body mass of 5%, either after 6 days of complete starvation or 11 days of a very low calorie diet (2.55 MJ/day). There were significant differences between the two groups in the synthesis rate of erythrocyte GSH in response to weight loss. Both the fractional and the erythrocyte synthesis rate of GSH decreased significantly (P<0.01) in the starvation group by 22% and 16% respectively. In contrast, no change in synthesis rates was observed in the very low calorie diet group (P>0.05). Total erythrocyte concentration of GSH was unaffected by the weight loss within both groups. These results suggest that erythrocyte GSH synthesis is depressed in response to a very rapid weight loss induced by fasting. An acute reduction in GSH synthesis in response to a rapid weight loss may constitute a risk factor during periods of increased GSH demands.

Amino Acids↗

PubMed2002

Does body mass play a role in the regulation of food intake?

It is widely believed that body fatness (and hence total body mass) is regulated by a lipostatic feedback system. This system is suggested to involve at least one peripheral signalling compound, which signals to the brain the current size of body fat stores. In the brain the level of the signal is compared with a desirable target level, and food intake and energy expenditure are then regulated to effect changes in the size of body fat stores. There is considerable support for this theory at several different levels of investigation. Patterns of body-mass change in subjects forced into energy imbalance seem to demonstrate homeostasis, and long-term changes in body mass are minor compared with the potential changes that might result from energy imbalance. Molecular studies of signalling compounds have suggested a putative lipostatic signal (leptin) and a complex network of downstream processing events in the brain, polymorphisms of which lead to disruption of body-mass regulation. This network of neuropeptides provides a rich seam of potential pharmaceutical targets for the control of obesity. Despite this consistent explanation for the observed phenomena at several different levels of enquiry, there are alternative explanations. In the present paper we explore the possibility that the existence of lipostatic regulation of body fatness is an illusion generated by the links between body mass and energy expenditure and responses to energy imbalance that are independent of body mass. Using computer-based models of temporal patterns in energy balance we show that common patterns of change in body mass following perturbation can be adequately explained by this 'non-lipostatic' model. This model has some important implications for the interpretations that we place on the molecular events in the brain, and ultimately in the search for pharmaceutical agents for alleviation of obesity.

Adipose Tissue↗