ReviewMetabolic surgery and gut hormones – A review of bariatric entero-humoral modulation
Introduction
Obesity has become a major contributor to the global burden of chronic disease, affecting virtually all ages and socioeconomic groups. Despite the application of a variety of traditional treatment therapies, including the promotion of good diet and exercise, the incidence of morbid obesity continues to rise, with a parallel increase in cardiac disease, and now not only affects the adult population but increasingly the paediatric demographic as well. This has led to focused research on introducing and refining an arsenal of obesity treatment modalities that recently has included bariatric surgery [1], an umbrella group of operations that are now also known as ‘metabolic surgery’. This treatment for obesity has shown the best results for rapid weight loss, which improves multi-systemic morbidity and mortality rates, with a corresponding decrease of health-care costs [2], [3].
The gastrointestinal tract is the largest endocrine organ in the body and it was through the discovery of gut hormones that the field of endocrinology initially developed. Bayliss and Starling first discovered ‘Secretin’ by demonstrating that an acidic infusion into a denervated jejunum led to pancreatic secretions, whilst a similar application of intravenous acid could not reproduce this [4]. Following the introduction of more advanced biochemical techniques in the 1960s, Secretin and a number of other gut hormones have been identified and now constitute the gastro-entero-pancreatic system. Many of these hormones have actions on the central nervous system and appetite, working through the so-called gut-brain axis. Of these, cholecystokinin (CCK) was the first hormone that was studied for its effect on satiety [5], [6].
The involvement of the central nervous system in the pathogenesis of obesity has been clearly identified through the identification of genetic variants at the FTO [7] (fat mass and obesity associated) and MC4R [8] (melanocortin 4 receptor) loci. However, the purpose for this article is to review the association between bariatric surgery and the role of surgically modulated gut hormones in altering appetite.
Section snippets
Hormonal control of central appetite regulation
Both long and short-term peripheral hormonal signals can influence feeding and eating behaviour. The hypothalamus has an important role in the control of appetite, although other regions also carry out processing of signals to contribute to this regulation. These include the nucleus tractus solitarius and the area postrema.
Hormonal signals and neural signals are integrated to coordinate both feeding behaviour and energy balance. Long term signals are mainly humoral and include information
Concepts in measuring gut hormones
Some gut hormones circulate as single peptides, whilst others are peptides of different lengths and amino acid patterns (such as gastrin). This requires the technique of radioimmunoassay to be directed, not only to one peptide, but also for plasma patterns characterized by a predominance of specific peptides that correspond to one hormone. Furthermore, it can also be useful to measure levels of biological precursors and processing intermediates to attain an increased diagnostic accuracy [13],
Bariatric or metabolic surgery
The word ‘bariatric’ stems from the combination of two Greek words, namely ‘baros’ and ‘iatrike’ which combine to literally mean ‘weight treatment’. The first procedures were derived independently in the mid-1950s by Arnold Kremen [15] and Richard Varco [16], [17]. The subsequent use of ‘bariatric surgery’ designates an umbrella term to account for all surgical procedures that are used to help in the reduction of excess weight.
These operations are further subdivided by surgeons into three
Obesity classification and current indications for bariatric procedures
The National Institutes of Health (NIH), The American College of Surgeons (ACS), The Society of Gastrointestinal Endoscopic Surgeons (SAGES), The American Society of Bariatric Surgeons (ASBS) and the United Kingdom's National Institute for Health and Clinical Excellence (NICE) have similar guidelines which identifies patients who could be considered for bariatric surgery. In general bariatric surgery is indicated in morbidly obese patients (Body Mass Index (BMI) > 40 kg/m2), or those with BMI >
Ghrelin
Ghrelin is a 28 amino acid peptide that is a peripherally active appetite stimulating hormone (Orexigen). It is released mainly from the gastric epithelial cells, although there is also some expression in the pituitary gland [34]. Circulating levels are inversely correlated with body weight and rise following weight loss. Furthermore, levels rise during fasting and fall rapidly after a meal. Calorie intake appears to be a primary regulator of plasma levels, although circulating levels are lower
Neurotensin
Neurotensin (NT) is a 13 amino acid gut peptide [150] and neurotransmitter that is found in many parts of the brain, where cell bodies containing NT closely interact with the mesolimbic, mesocortical and nigro-striatal dopamine (DA) circuits [151]. It has been demonstrated to reduce food intake, and its expression is down-regulated in leptin deficiency (ob/ob mice) [152].
Five out of six bypass studies [121], [139], [140], [149], [153], [154] reveal that NT is significantly increased after
Glucagon-like peptide-1
Glucagon-like peptide-1 (GLP-1) is both a gut hormone and a neuropeptide produced by the post-translational processing of the pre-proglucagon gene. It is co-secreted by the L cells of the gastrointestinal tract with PYY and Oxyntomodulin. It is cleaved as a 36 or 37 amino acid peptide and gains further biological activity by truncation at the N-terminal [156]. Plasma levels increase rapidly after a meal, although its circulating half-life is less than 5 min. This occurs as due to its renal
Other hormones and animal models
A number of other hormones have been measured before and after bariatric operations, although they occur in such few studies that it becomes difficult to observe any trends as how metabolic surgery can modulate them. A few notable exceptions are mentioned below.
Vasoactive intestinal peptide (VIP), Serotonin (5HT) and Neuropeptide Y (NPY) are all gut and brain hormones. VIP increases gastrointestinal secretion and smooth muscle relaxation to augment intestinal motility, whereas Serotonin reduces
Conclusions
Gut peptides may be a major contributor through which the gastrointestinal tract can communicate with the brain to regulate feeding behaviour and energy balance. This gut-brain axis has developed a sophisticated collection of peptides with which to relay its messages. These can travel directly via the nervous system, the systemic circulation or both to deploy energetic information to the brainstem and higher food regulatory centres. Bariatric or Metabolic surgical procedures are not all the
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