Review
Mechanisms facilitating weight loss and resolution of type 2 diabetes following bariatric surgery

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Bariatric surgery is the most effective treatment modality for obesity, resulting in durable weight loss and amelioration of obesity-associated comorbidities, particularly type 2 diabetes mellitus (T2DM). Moreover, the metabolic benefits of bariatric surgery occur independently of weight loss. There is increasing evidence that surgically induced alterations in circulating gut hormones mediate these beneficial effects of bariatric surgery. Here, we summarise current knowledge on the effects of different bariatric procedures on circulating gut hormone levels. We also discuss the theories that have been put forward to explain the weight loss and T2DM resolution following bariatric surgery. Understanding the mechanisms mediating these beneficial outcomes of bariatric surgery could result in new non-surgical treatment strategies for obesity and T2DM.

Section snippets

Bariatric surgery

The obesity pandemic has become a global burden and is now a leading cause of morbidity and mortality. To date, non-surgical means of weight reduction have been ineffective in producing sustained weight loss. Currently, bariatric surgery is the most effective treatment for obesity and is indicated for patients with a body mass index (BMI) >40 kg/m2, or for individuals with a BMI >35 kg/m2 and significant obesity-related comorbidities. A range of different bariatric procedures are available, some

Bariatric procedures

Bariatric procedures are divided into three categories: restrictive, malabsorptive and hybrid procedures, the latter combining gastric restriction and malabsorption (Figure 1). Restrictive procedures, such as gastric banding (GB), vertical banded gastroplasty (VBG) and sleeve gastrectomy (SG) reduce gastric volume (Figure 1). GB entails inserting a synthetic band with an inner inflatable balloon around the stomach below the gastro-oesophageal junction. The inner balloon diameter and hence the

Malabsorption

In 1954 Kremen et al. reported that surgical bypass of the distal small intestine in dogs reduced food absorption and resulted in weight loss. Consequently, they advocated intestinal bypass surgery as a treatment for human obesity [8], the rationale being that reduced nutrient absorption results in weight loss. However, as early as 30 years ago, studies indicated that malabsorption was not the major cause of weight loss in patients that had undergone intestinal bypass surgery [9]. For example,

Gut hormones and bariatric surgery

The gut is the largest endocrine organ in the body, producing hormones that have important sensing and signalling roles in the regulation of appetite and energy homeostasis. Bariatric surgical procedures alter the circulating concentrations of several gut hormones, including GLP-1, PYY and ghrelin. So far, reports of the effect of different surgical procedures on all three hormones have been controversial. Differences in surgical techniques, research methodologies, sample assays and blood

GLP-1 levels after bariatric surgery

GLP-1 is a peptide synthesised by the L-cells of the distal gut and released in response to nutrient ingestion [27]. The main physiological action of GLP-1 is stimulation of glucose-dependent insulin secretion [27]. In addition, GLP-1 exhibits appetite and body weight regulatory properties 29, 30, 31 (Box 1).

The first observations that circulating GLP-1 levels increase after bariatric surgery were made three decades ago. In the late 1970 s, Barry et al. reported elevated enteroglucagon levels

PYY levels after bariatric surgery

PYY is a peptide hormone synthesised by the L-cells of the distal gastrointestinal tract and released in response to food ingestion [21]. PYY suppresses appetite and exerts regulatory properties on body weight and glucose homeostasis [21]. Two forms of the peptide have been described: total PYY1-36 and PYY3-36 [21] (Box 2).

As both GLP-1 and PYY are secreted by the L-cells of the distal gut, it is no surprise that postoperative levels of the peptides parallel one another. The first observation

Ghrelin as a mediator of weight loss and T2DM resolution following bariatric surgery

Ghrelin is a unique orexigenic hormone released from the stomach in response to nutrient ingestion [21]. Additional properties of ghrelin include a regulatory role in body weight, energy and glucose homeostasis [21] (Box 3). Ghrelin undergoes post-translational acylation which is necessary for its conversion to its active form, acyl-ghrelin [21] (Box 3). Several studies have assessed the impact of bariatric surgery on circulating ghrelin profiles, measuring either total (acyl- and

Concluding remarks

Weight loss and resolution of T2DM after bariatric surgery appear to be the composite outcome of multiple contributing mechanisms. Current evidence suggests that the key mechanism behind the weight loss and metabolic beneficial effects is increased hindgut stimulation due to enhanced nutrient delivery and subsequent exaggerated release of hindgut hormones, such as GLP-1 and PYY. Future studies in transgenic mice and humans evaluating alterations in gut hormones after bariatric surgery and the

Acknowledgments

We would like to thank Karima Yousseif for the illustrations. A.Y. is funded by the UCL/UCLH Comprehensive Biomedical Centre. We apologise to those authors whose original papers could not be cited because of space constraints.

Glossary

Body mass index (BMI)
a measure of a person's weight in relation to their height, it is used to estimate body fat. BMI is calculated by dividing body weight (in kilograms) by the square of height (in metres). Normal BMI is defined as 18–24.9 kg/m2, overweight as BMI 25–29.9 kg/m2 and obesity as BMI >30 kg/m2.
Entero–entero anastomosis
an anastomosis between two pieces of intestine.
Foregut
the anterior portion of the alimentary tract. For the purpose of this review, the term foregut refers to the

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