How May Gut Hormones Change after Laparoscopic Sleeve Gastrectomy?
Laparoscopic sleeve gastrectomy is a comparatively new bariatric procedure, first introduced as an isolated technique in the early 1990s. Since then it has gained popularity as a result of its safety and low complication rate, making it particularly suitable for the most severely obese individuals and other higher-risk populations. Classified as a restrictive procedure, laparoscopic sleeve gastrectomy involves modification of the gastric fundus, which expresses various hormones associated with hunger and satiety, insulin secretion and energy balance, and is known to induce rates of type 2 diabetes remission comparable to those observed following malabsorbtive procedures such as the Roux-en-Y gastric bypass (RYGB). It is therefore likely that metabolic factors are implicated in laparoscopic sleeve gastrectomy induced weight loss and resolution of obesity-related conditions.
Glucagon-Like Peptide-1 and Peptide YY
Glucagon-like peptide-1 (GLP-1) one of several gut hormones classed as incretins, involved in stimulation of insulin release from the pancreas in response to enteral nutrient intake. Alongside peptide YY (PYY), also produced by the L cells of the distal gut, GLP-1 is understood to cause delayed gastric emptying. PYY additionally inhibits gastrointestinal motility, whilst GLP-1 inhibits glucagon secretion. Both hormones are thought to reduce food intake by promoting satiety.
Obesity is understood to result in reduced postprandial levels of GLP-1 and PYY levels, and it has been suggested that this could promote increased food intake as a result of impaired satiety. There is evidence to suggest that postprandial levels of GLP-1 and PYY are increased within 6 weeks of laparoscopic sleeve gastrectomy surgery, and remain elevated for at least 12 months postoperatively, whilst fasting levels of GLP-1 remain unchanged. There is a lack of consensus about the effects of laparoscopic sleeve gastrectomy upon fasting PYY, most likely as a result of differing study protocols. There is also some limited data to support other patterns of postprandial GLP-1 and PYY secretion following laparoscopic sleeve gastrectomy, and it has been hypothesized that differences in surgical implementation of laparoscopic sleeve gastrectomy could affect speed of gastric emptying and therefore influence gut hormone secretion to account for these variations.
The precise mechanisms underlying improved postprandial secretion of GLP-1 and PYY following laparoscopic sleeve gastrectomy have yet to be established. One theory is that the increased rate of gastric emptying and decreased gastric acid secretion observed after laparoscopic sleeve gastrectomy may lead to undigested food reaching the L cells of the distal gut more rapidly. It has also been hypothesized that hormonal secretion by the L cells may be mediated by nutrient-related signals transmitted between the proximal and distal gut via fluid or neuronal pathways.
Predominantly secreted by the gastric fundus, ghrelin has various effects upon food intake, acting to increase appetite and influencing chewing time, taste preferences and food perception, as well as increasing gastrointestinal motility and decreasing insulin secretion. In non-obese individuals, ghrelin levels are highest immediately prior to a meal and drop rapidly upon initiation of eating. Conversely, obesity is associated with reduced ghrelin levels, with food intake failing to modulate levels of plasma ghrelin. Dietary-induced weight loss is linked to increased ghrelin secretion, which has been postulated to contribute to the poor long-term success rates of dietary weight loss programs by promoting increased food consumption, although this remains unproven.
Laparoscopic sleeve gastrectomy involves resection of the gastric fundus, and the procedure appears to permanently inhibit ghrelin production in the majority of individuals within days of surgery. In contrast, laparoscopic adjustable gastric banding – also classed as a restrictive procedure - is associated with increased ghrelin secretion. Several studies have reported laparoscopic sleeve gastrectomy to precipitate greater reduction in hunger than laparoscopic adjustable gastric banding, with normal gastric emptying occurring in both cases. It has yet to be established whether this is due to differences in ghrelin secretion or to some other factor. Ghrelin may also be implicated in the superior efficacy of laparoscopic sleeve gastrectomy in relation to laparoscopic adjustable gastric banding in terms of type 2 diabetes resolution, due to its effects upon insulin secretion.
Pancreatic polypeptide (PP) is predominantly secreted by the PP cells of the pancreas, and has been linked to appetite modulation and decreased consumption of food. Secretion of PP is initiated by food intake, occurring in reaction to efferent vagal nerve activity and gastrointestinal responses to caloric load. There is evidence to suggest that postprandial plasma levels of PP rise in proportion to calories ingested, but the relationship between PP levels and obesity is not clear and studies examining the differences between PP levels in obese and non-obese subjects have produced confounding results.
Laparoscopic sleeve gastrectomy is thought to precipitate changes in PP meal response, with elevated levels of PP observed postprandially at up to 12 months following surgery. Laparoscopic sleeve gastrectomy is also associated with increased speed of gastric emptying, and it has been suggested that this may partly account for enhanced PP secretion. The effects of laparoscopic sleeve gastrectomy-induced changes in postprandial PP are unknown, but could involve alterations to energy metabolism and food intake.
Insulin is produced by the beta cells of the pancreas and is responsible for regulating glucose uptake and inhibiting glucagon release. Lack of insulin or impaired insulin sensitivity can lead to diabetes.
Laparoscopic sleeve gastrectomy is thought to precipitate early significant improvements in glucose homeostasis, similar to those observed following RYBG, with superior resolution rates of type 2 diabetes to laparoscopic adjustable gastric banding. Whilst postsurgical changes to gut hormone response may be implicated, the majority of studies suggest that weight loss is predominantly responsible. At least one study involving non-diabetic subjects has reported greater improvements in post-laparoscopic sleeve gastrectomy insulin secretion than those observed following dietary interventions resulting in comparable weight loss, but the impact of diabetic status upon these results is not clear.
Leptin is a protein hormone produced almost exclusively by adipose tissue. It is known to inhibit food intake and is associated with insulin resistance via its inhibitory role in glucose-stimulated insulin production. Obesity is associated with an increase in circulating leptin, with levels positively correlated with BMI and body fat content. Weight loss achieved by either surgical or dietary interventions is associated with decreased leptin levels, whilst sustained exposure to high concentrations of leptin can lead to desensitization, limiting its ability to control appetite. It has been suggested that leptin resistance may contribute to the pathogenesis of obesity.
Most studies investigating the metabolic effects of laparoscopic sleeve gastrectomy have reported no significant change in leptin meal response postoperatively, whilst circulating levels of leptin are thought to decrease in line with weight loss, suggesting that laparoscopic sleeve gastrectomy confers no particular advantage over dietary-induced weight loss in terms of leptin sensitivity.
Adiponectin is an adipose-specific peptide hormone thought to mediate the relationship between obesity and chronic inflammation. It improves insulin sensitivity and promotes glucose uptake, and when present at low levels is associated with development of insulin resistance and type 2 diabetes. Obesity is negatively correlated with adiponectin levels, whilst weight loss achieved through dietary intervention or bariatric surgery leads to increased adiponectin secretion.
Post-bariatric adiponectin levels are generally understood to vary depending upon the type of procedure, with most studies agreeing that levels are highest after RYGB compared to purely restrictive procedures, which could account for its relative success in resolving insulin sensitivity and type 2 diabetes. Some studies have also reported similarly elevated levels of adiponectin following laparoscopic sleeve gastrectomy, which may be implicated in its relatively early delivery of glucose homeostasis postoperatively, although the mechanisms underlying these effects remain unclear.
The association between impaired fertility and sexual function in males is thought to be mediated by a number of hormonal factors including elevated levels of estrogen, and reduced levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Adipose secretion of estrogen is known to suppress LH, which is necessary for testosterone production, resulting in a negative correlation between testosterone and BMI.
Whilst there is some evidence to suggest that weight loss can ameliorate obesity-related fertility issues in males, the specific effects of Laparoscopic Sleeve Gastrectomy upon male fertility are not currently understood.
Obesity is associated with anovulation, subfecundity and poor pregnancy outcomes. Polycystic ovarian syndrome (PCOS), as characterised by anovulation in the presence of elevated testosterone levels and/or enlarged ovaries covered in multiple small cysts, is strongly associated with obesity and insulin resistance.
Obese women typically exhibit an altered hormonal profile in which levels of insulin and luteinizing hormone (LH) are elevated, the ratio of LH to follicle stimulating hormone (FSH) is abnormal and mid-luteal phase progesterone is low. There is also some evidence to suggest leptin deficiency as an independent cause of infertility in obese females. Leptin receptors have been identified in the uterus and ovarian follicles and the hormone is present in mature oocytes, but its specific role in female fertility remains unclear.
Weight loss is known to increase fertility and reduce obstetric complications in premenopausal women, with bariatric surgery acknowledged as an effective means of promoting sustained weight loss that is not associated with additional complications during pregnancy, so long as an appropriate interval exists between surgery and conception.
Insulin resistance is significant factor in PCOS and can lead to impaired progesterone release, which has been implicated in the increased miscarriage rate observed in obese women. Laparoscopic sleeve gastrectomy and other bariatric procedures are known to have a positive effect upon insulin resistance and glucose sensitivity, but whether the endocrine effects of specific bariatric procedures have a particular impact upon female fertility has yet to be elucidated. The available evidence indicates that weight loss is the most significant predictor of post-surgical fertility in women of reproductive age.