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Obesity and assessment for metabolic surgery
Introduction
World Health Organization (WHO) statistics reveal that 1.9 billion adults (39%) above 18 years of age were overweight, an estimated 650 million adults (13%) worldwide were obese in 2016, and 39 million children under 5 years of age were overweight or obese in 2020 ( Figs. 17.1 and 17.2 ).
Medical management with caloric restriction, diets, and drug therapy do not provide sustained long-term weight loss in many patients. Metabolic surgery is currently the best treatment that provides long-term weight loss maintenance and comorbidity control. In the Swedish Obese Subjects (SOS) intervention study, at 10 years follow-up the surgical group had 16% weight loss compared to 1.6% weight gain for patients managed conservatively.
Metabolic surgery is the best treatment for obesity that provides long-term weight loss and maintenance. The SOS intervention study demonstrated that at 10-year follow-up, the surgical group had 16% weight loss compared to 1.6% weight gain for patients managed conservatively.
The first metabolic procedures such as jejuno-ileal bypass and vertical banded gastroplasty have now been superseded by the most commonly performed procedures, namely Roux-en-Y gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), laparoscopic adjustable gastric banding (LAGB), and biliopancreatic diversion (BPD) (with or without a duodenal switch [DS]). Techniques have also now evolved from open to laparoscopic techniques. The overall 30-day mortality rates after metabolic surgery can be as low as 0.3% in experienced high-volume centres, making it safe as well as highly effective.
Pathophysiology of obesity and obesity-related diseases
Obesity is a risk factor for many obesity complications:
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Type 2 diabetes mellitus (T2DM) and micro- and macrovascular complications
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Dyslipidaemia
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Hypertension
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Cardiovascular disease
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Non-alcoholic fatty liver disease (NAFLD)
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Non-alcoholic steatohepatitis (NASH)
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Obstructive sleep apnoea (OSA)
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Asthma
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Musculoskeletal pain and function
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Gastro-oesophageal reflux disease (GORD)
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Polycystic ovary syndrome (PCOS) symptoms
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Infertility
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Urinary incontinence
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Cancer, e.g. breast, endometrial, colon, oesophageal, hepatocellular
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Psychosocial functioning.
We now understand that obesity and its related complications are metabolic diseases involving complex gut–brain–endocrine (GBE) and adipocyte–brain–endocrine interactions.
The GBE axis is fundamental for energy homeostasis. Enteroendocrine cells (EECs) sense luminal factors, such as absorbed nutrients, via sensory transporters and various cell membrane receptors. EECs are activated to secrete gut hormones such as oxyntomodulin (OXM) and glucagon-like peptide 1 (GLP-1), which alert the central nervous system (CNS) that nutrients are in the gut lumen via endocrine (circulation or lymphatics) or paracrine (activation of enteric, vagal and spinal afferent sensory neurons via local receptors) mechanisms. This signalling pathway activates metabolic control centres in the hindbrain and hypothalamus to control energy homeostasis, resulting in responses such as reduced food intake, increased energy expenditure (OXM), increased satiety, insulin release, and glucose homeostasis, slowing gastrointestinal (GI) motility, gut secretions, and nutrient utilisation.
It is now understood that metabolic surgery is not purely weight loss surgery. Metabolic surgery results in anatomical alterations that produce complex physiological interactions involving signalling between the gut and the brain, as well as adipocytes and the brain.
Adipose tissue consists of brown adipose tissue (involved in non-shivering thermogenesis) and white adipose tissue (which stores cholesterol and triglycerides [TGs], and acts as an endocrine and immune organ). An increase in the fat mass associated with obesity results in adipocyte and adipose tissue dysfunction, termed adiposopathy (or ‘sick fat’). White adipocytes produce immune factors such as leptin and adiponectin (which has anti-inflammatory and antidiabetic properties); growth factors; adipocytokines such as IL-6 and tumour necrosis factor (TNF); and enzymes such as 11β-hydroxysteroid dehydrogenase. These contribute to inflammation and have a significant effect on obesity-related complications. Metabolic surgery has been shown to result in favourable effects on these factors. , Understanding the mechanisms of metabolic surgery has significantly furthered our knowledge of the pathophysiology of obesity and its related comorbidities.
The mechanisms of action and rationale for metabolic procedures
Metabolic procedures were originally developed as purely mechanically restrictive and/or malabsorptive procedures. However, the contribution of restriction and malabsorption has been shown to be minimal. We now understand that they are metabolic procedures involving complex GBE and adipocyte–brain signalling that regulates appetite, satiety, weight, glucose metabolism, and other immunological processes.
Weight loss post metabolic surgery
RYGB and VSG are the most commonly performed procedures and cause a 25–35% total body weight loss and maintenance. , The mechanisms underlying this include reduced food intake and increased energy expenditure.
Food intake
After metabolic surgery, in contrast to low-calorie diets, patients report decreased pre-meal hunger and increased satiety. Various components of the GBE axis can explain this reduction in food intake.
Gut hormones
Gut peptides are secreted from EECs that reside within the intestinal epithelium and are often referred to as satiety hormones. Metabolic surgery can increase the number of gut peptide-expressing EECs (e.g. L cells), and therefore postprandial gut peptide secretion (e.g. GLP-1, GLP-2, and peptide YY [PYY]). Patients with the highest postprandial levels of satiety hormones lose the most weight post RYGB. Changes in nutrient concentrations (higher in the distal segments) and faster delivery to the distal ileum post RYGB give stimulus to EECs to release these ‘satiety’ hormones, resulting in increased satiety, reduced food intake, and sustained weight loss. In VSG, faster gastric emptying has been used to explain the rise in satiety hormones. Both PYY and GLP-1 act at the arcuate nucleus (ARC) additively to suppress food intake , but also via vagal afferents terminating at the nucleus tractus solitarius (NTS) to signal satiety. GLP-1 also slows gastric emptying, inhibits glucagon release, and acts on the pancreas to secrete insulin (incretin effect).
Neural mechanisms
Vagus signalling
The vagus nerve is an important regulator of food intake and body weight. Vagal afferents can be activated by the paracrine action of gut hormones in response to ingested nutrients or by mechanical stretch from the volume of food ingested. The enteric nervous system may also activate spinal afferents and gut vagal afferents in response to gut hormones, as seen in rodents. Post RYGB there is evidence that vagal signalling may play a role in satiation, reduction in signalling of ghrelin, reduction in meal size, and altered food preferences. After LAGB, vagal signalling may reduce food intake and weight loss by reducing hunger and inducing satiation via neural mechanisms. After VSG, hyperexcitation of NTS synapses and increased glutamate release due to vagal signalling may be the mechanism for reducing food intake, as suggested from rodent studies.
Hypothalamic signalling and surgery
Vagal afferents synapse in the NTS of the dorsal vagal complex of the brain stem , and the NTS integrates and relays vagal signals to the ARC of the hypothalamus. Many gut peptides influence energy homeostasis through ARC pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons and neuropeptides, showing a clear association between the GBE axis and control of feeding behaviour after metabolic surgery.
Gut microbiota
After RYGB, the gut microbiota ratio observed in patients is reversed, with a reduced Firmicutes : Bacteroides ratio, as well as increased Gammaproteobacteria and Escherichia coli. When the gut microbiota from mice post RYGB was transferred to germ-free mice, their body weight and body fat decreased. Microbial fermentation of polysaccharides into short-chain fatty acids (SCFAs) may explain this observation. SCFAs and bacterial antigens interact with EECs and stimulate gut hormone production associated with reduction in food intake in mice. After surgery in humans some gut microbes have been directly linked to improvement of weight, metabolic status, and energy intake, while Faecalibacterium prausnitzii gut species have been correlated with a reduction in inflammation.
Bile acids
Total plasma bile acids (BAs) are higher after RYGB, BPD, and VSG, but not LAGB, and their levels negatively correlate with postprandial glucose levels. BAs are commonly suggested as mediators of the early metabolic beneficial effects of bariatric surgery, which is based on the consistent finding after bypass metabolic surgery that circulating BAs are increased in both fasting and postprandial conditions. , After RYGB, BAs are also found to positively correlate with several other metabolically active peptides, including adiponectin, PYY, and GLP-1. , BAs remain high for 3–4 years post-surgery and could play a role in intestinal hypertrophy, gut hormone secretion (GLP-1 and PYY) through G-protein–coupled receptor TGR5, lipid and glucose metabolism, as well as contribute to changes in gut flora. ,
Changes in food preference and food reward
Hedonic hunger is reduced after RYGB, with increased intake of fruit and vegetables and no fixation on energy-dense sweet and fatty foods; similar changes in food preferences are seen after VSG. Both VSG and RYGB lead to an increase in gut hormones GLP-1 and PYY, which may have effects on central gustatory pathways related to feeding and reward: altered quality of tastants, palatability, and hedonic properties of sweet and fat stimuli. Conditioned food avoidance rather than conditioned food aversion appears to be the main underlying mechanism for the changes observed in humans and rodents.
Energy expenditure
Studies assessing energy expenditure after metabolic surgery show varying results on total energy expenditure, but have consistently demonstrated that diet-induced energy expenditure is increased after RYGB when compared with controls. BAs are increased after RYGB and may modulate energy expenditure through their actions on brown adipose tissue or skeletal muscle. The precise mechanism causing increases in diet-induced thermogenesis after RYGB is yet to be elucidated.
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