Adam Cunliffe

The Role of Diet and Exercise for the Maintenance of Fat-Free Mass and Resting Metabolic Rate During Weight Loss

The incidence of obesity is increasing rapidly. Research efforts for effective treatment strategies still focus on diet and exercise programmes, the individual components of which have been investigated in intervention trials in order to determine the most effective recommendations for sustained changes in bodyweight. The foremost objective of a weight-loss trial has to be the reduction in body fat leading to a decrease in risk factors for metabolic syndrome. However, a concomitant decline in lean tissue can frequently be observed. Given that fat-free mass (FFM) represents a key determinant of the magnitude of resting metabolic rate (RMR), it follows that a decrease in lean tissue could hinder the progress of weight loss. Therefore, with respect to long-term effectiveness of weight-loss programmes, the loss of fat mass while maintaining FFM and RMR seems desirable.Diet intervention studies suggest spontaneous losses in bodyweight following low-fat diets, and current data on a reduction of the carbohydrate-to-protein ratio of the diet show promising outcomes. Exercise training is associated with an increase in energy expenditure, thus promoting changes in body composition and bodyweight while keeping dietary intake constant. The advantages of strength training may have greater implications than initially proposed with respect to decreasing percentage body fat and sustaining FFM. Research to date suggests that the addition of exercise programmes to dietary restriction can promote more favourable changes in body composition than diet or physical activity on its own. Moreover, recent research indicates that the macronutrient content of the energy-restricted diet may influence body compositional alterations following exercise regimens. Protein emerges as an important factor for the maintenance of or increase in FFM induced by exercise training. Changes in RMR can only partly be accounted for by alterations in respiring tissues, and other yet-undefined mechanisms have to be explored. These outcomes provide the scientific rationale to justify further randomised intervention trials on the synergies between diet and exercise approaches to yield favourable modifications in body composition.

Attenuation of plasma annexin A1 in human obesity

Obesity‐related metabolic disorders are characterized by mild chronic inflammation, leukocyte infiltration, and tissue fibrosis as a result of adipocytokine production from the expanding white adipose tissue. Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein, which modulates systemic anti‐inflammatory processes and, therefore, may be altered with increasing adiposity in humans. Paradoxically, we found that plasma AnxA1 concentrations inversely correlated with BMI, total percentage body fat, and waist‐to‐hip ratio in human subjects. Plasma AnxA1 was also inversely correlated with plasma concentrations of the acute‐phase protein, C‐reactive protein (CRP), and the adipocytokine leptin, suggesting that as systemic inflammation increases, anti‐inflammatory AnxA1 is reduced. In addition, AnxA1 gene expression and protein were significantly up‐regulated during adipogenesis in a human adipocyte cell line compared to vehicle alone, demonstrating for the first time that AnxA1 is expressed and excreted from human adipocytes. These data demonstrate a failure in the endogenous anti‐inflammatory system to respond to increasing systemic inflammation resulting from expanding adipose tissue, a condition strongly linked to the development of type 2 diabetes and cardiovascular disease. These data raise the possibility that a reduction in plasma AnxA1 may contribute to the chronic inflammatory phenotype observed in human obesity.—Kosicka, A., Cunliffe, A. D., Mackenzie, R., Gulrez Zariwala, M., Perretti, M., Flower, R. J., Renshaw, D. Attenuation of plasma annexin A1 in human obesity. FASEB J. 27, 368–378 (2013). www.fasebj.org

THE ROLES OF MELANIN CONCENTRATING HORMONE IN ENERGY BALANCE AND REPRODUCTIVE FUNCTION: ARE THEY CONNECTED?

Melanin-concentrating hormone (MCH) is an anabolic neuropeptide with multiple and diverse physiological functions including a key role in energy homoeostasis. Rodent studies have shown that the ablation of functional MCH results in a lean phenotype, increased energy expenditure and resistance to diet-induced obesity. These findings have generated interest among pharmaceutical companies vigilant for potential anti-obesity agents. Nutritional status affects reproductive physiology and behaviours, thereby optimising reproductive success and the ability to meet energetic demands. This complex control system entails the integration of direct or indirect peripheral stimuli with central effector systems and involves numerous mediators. A role for MCH in the reproductive axis has emerged, giving rise to the premise that MCH may serve as an integratory mediator between those discrete systems that regulate energy balance and reproductive function. Hence, this review focuses on published evidence concerning i) the role of MCH in energy homoeostasis and ii) the regulatory role of MCH in the reproductive axis. The question as to whether the MCH system mediates the integration of energy homoeostasis with the neuroendocrine reproductive axis and, if so, by what means has received limited coverage in the literature; evidence to date and current theories are summarised herein.

Melanin-concentrating hormone in peripheral circulation in the human

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role.

Metabolic effects of long-term oral ingestion of l -histidine in overweight and obese men

Animal studies have revealed that histidine (L-hist) intake and neuronal histamine action play a key role in thermoregulation, energy expenditure and feeding behaviour by different mechanisms (1‐5) . There is a need to reproduce studies of peripheral administration of the essential amino acid L-hist in human subjects to observe any role in key metabolic functions and any possible implications in the treatment of obesity and associated disorders. The aim of the present study was to examine the effect of L-hist on risk factors for the metabolic syndrome. Eighteen male participants with BMI > 25 kg/m 2 were recruited for an 8-week randomised single blinded placebo-controlled study (intervention 25 mg L-hist/kg per d (Lamberts Healthcare, UK); placebo 45 mg Casilan-90 /kg per d (Complan Foods Ltd, UK). Measurements were carried out at 0, 4 and 8 weeks and included BMR 6 , mean skin and core temperature, total cholesterol, HDL-cholesterol, LDL-cholesterol, fasting blood glucose (FBG) 7 , insulin, leptin, NEFA and percentage body fat. Analysis of data was performed using ANOVA. Results of the study revealed an interesting trend of significantly decreased weight at 4 weeks (P = 0.046) and 8 weeks (P = 0.003) when compared with baseline weight, irrespective of the type of supplementation. BMR steadily increased over the 8-week period and at a more rapid rate with L-hist supplementation. FBG decreased slightly with L-hist (3.4% from baseline) compared with the increase (5 % from baseline) observed post placebo intake. An increase in plasma insulin levels was found in the placebo group, with a 6.3 % decrease with L-hist (although this effect was not significant). Plasma NEFA concentrations increased post L-hist intake, indicating elevated lipolysis.