Obesity, defined as a body mass index (BMI) ≥30 kg/m2, has become a worldwide epidemic. The prevalence of obesity has been on the rise, reaching 42.4% in 2017-2018 in the United States. Obesity can contribute towards multiple cardiometabolic co-morbidities, with debilitating consequences such as heart disease, type 2 diabetes, and certain types of cancer. Bariatric surgery has been a very effective method in substantially improving weight, and numerous studies have focused on intestinal adaptation after bariatric procedures. A number of structural and functional changes in the GI tract have been reported postsurgery, which could be responsible for the altered hormonal responses. Understanding hormonal changes in obese women is crucial for identifying potential interventions to mitigate risks associated with obesity, such as heart disease, type 2 diabetes, and certain types of cancer.
Bariatric Surgery and Weight Loss
The weight reductive effects of bariatric surgery have been well documented over the past decades, and bariatric surgery remains currently the most effective weight loss method mainly by GI tract volume restriction and/or beneficial metabolic sequelae. Bariatric procedures, such as Roux-en-Y gastric bypass and vertical sleeve gastrectomy, cause substantial and durable weight loss in both humans and rodents. Lately, these surgical interventions have also been termed metabolic due to the substantive metabolic changes beyond body weight loss alone. Bariatric surgery usually leads to a body weight reduction of 25% to 35% within 1-2 years, primarily through the restriction of food intake and/or malabsorption. Various mechanisms have been proposed to explain the weight loss achieved through BS, and the restriction of food intake due to the reduction in the size of the gastric pouch is an important contributor to this, as it results in a reduction in caloric intake. Decreased appetite and early satiety are likely to be not only due to the decrease in gastric space but may be contributed to by neuroendocrine modulation after BS. Complex interactions between the brain and hormone productions in the gastrointestinal (GI) tract, pancreas, liver and adipose tissue are considered to contribute substantially to the effects of BS.
Common Bariatric Procedures
- Gastric banding (GB): Includes the placement of a silicone ring around the stomach to create a small upper gastric pouch at the bottom of the oesophagus.
- Roux-en-Y gastric bypass (RYGB): A small gastric pouch is created, draining into the jejunum (alimentary limb) causing nutrients to bypass the pylorus and duodenum. The bile and pancreatic juices drain into the duodenum and jejunum as normal (biliopancreatic limb) but are only mixed with food after the anastomosis of the alimentary and biliopancreatic limbs to create the common limb.
- Sleeve gastrectomy (SG): Involves creating a long, thin longitudinal gastric pouch or sleeve. This reduces the volume of the stomach by approximately 80% but leaves the pylorus intact.
Impact on Gastrointestinal Hormones
The metabolic effects of bariatric surgery have been attributed by many to changes in the secretion of gastroenteropancreatic peptides although additional mechanisms have been proposed.
Gastrin: Following RYGB, postprandial gastrin levels fall both in the first 2 weeks postoperatively and over the first year. One study demonstrated increased cell proliferation rate in the epithelium of the excluded gastric antrum coupled with a reduction in the number of G cells. A study of patients following GB demonstrated no change in fasting gastrin concentrations 6-12 months after surgery. Others have showed that SG may be associated with increased gastrin levels in both human and rodents.
Ghrelin: The effect of bariatric procedures appears to have variable effects on ghrelin secretion, possibly due to the altered passage of ingested nutrients through the gastric fundus where the ghrelin-producing cells are predominantly located and additionally due to small sample size of the existing studies. Six months after surgery, patients with GB and lifestyle group had similar ghrelin levels, whereas patients with RYGB had a significant decrease. Others, however, have demonstrated increased ghrelin levels in humans or rodents following RYGB. Weight loss surgery impacts the hunger hormone ghrelin, produced in the stomach. During bariatric surgery, the surgeon removes a large portion of the stomach. This causes most of the ghrelin in the body to be removed.
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Cholecystokinin (CCK): Several studies have shown an increase in CCK levels postprandially after RYGB in response to a mixed meal. Mans et al. showed that SG resulted in enhanced CCK levels and increased satiety in morbidly obese patients versus matched controls. SG was associated with a much larger CCK increase compared to the RYGB group. The effect of SG in CCK secretion was evident 1 week postoperatively and gained in magnitude over the first year.
Glucose-dependent insulinotropic polypeptide (GIP): RYGB is found in some studies to cause a reduction in postprandial GIP secretion due to the restriction of nutrient passage through the duodenum and jejunum, and this effect may be enhanced in patients with type 2 diabetes mellitus (T2DM). The RYGB group had increased GIP levels postsurgically whereas there were no observed changes in the GB group. Similar findings have been reported by others after GB.
Glucagon-like peptide-1 (GLP-1): Despite the lack of evidence indicating increased GLP-1 concentrations following bariatric surgery, postprandial GLP-1 levels are increased following GB, SG and RYGB. It is believed that it may be associated to the passage of more intact nutrients to the ileum through anatomical changes or increased intestinal transit. Dirksen et al. showed that levels of GLP-1 were higher in patients who lost more weight, compared to those with poor weight loss.
Glucagon-like peptide 2 (GLP-2): Taqi et al., in an experimental study, demonstrated a significant increase in the GLP-2 levels after gastric bypass in rats. LeRoux et al., in a human prospective study, demonstrated a significant increase in the postprandial levels of GLP-2 after gastric bypass, with a secretion peak observed 6 months after the procedure.
Peptide YY (PYY): PYY is a short (36-amino acid) peptide released by L enteroendocrine cells in the distal small intestine and colon in response to feeding.
Impact on Reproductive Hormones
Alterations in reproductive hormones have been implicated in fertility issues for both men and women. In women, changes in the balance of the hypothalamic-pituitary-gonadal axis can affect the regularity of menstrual cycles and overall reproductive function. Women with obesity often have elevated levels of androgens, LH, and insulin, and reduced levels of FSH, which can contribute to conditions like polycystic ovary syndrome (PCOS).
The effects of bariatric surgery on reproductive hormones are not well understood. Some studies suggest that bariatric surgery can improve reproductive hormone profiles in women with obesity.
Other Hormonal Changes After Bariatric Surgery
Taste and Smell: You may notice that certain foods you enjoyed eating before weight loss surgery are no longer appetizing. Similarly, foods that you despised eating may now be your favorites. In one study, 73% of patients reported changes in their taste buds, and 50% reported changes in their smell.
Mood: Our mood is partially impacted by serotonin, a nerve cell found mainly in the digestive system. A diet high in carbohydrates increases serotonin synthesis, while proteins block this response in the brain. After bariatric surgery, your serotonin production will be low when you eat a high-protein and low-carb diet.
Acne: Bariatric surgery itself does not cause acne, but instead, it is related to the hormonal and dietary changes that occur. Healthy-looking skin has a lot to do with your hormones and what you eat.
Read also: The Divinity Hormone Explained
The Role of the Nervous System in Appetite and Energy Regulation
Research has shown that the central nervous system (CNS) plays a fundamental role in modulating appetite, satiety and energy balance by acting through both the brain and the peripheral organs. CNS regulation of appetite and body weight in the human brain is a complex process controlled by several neural systems that integrate myriad cognitive, emotional, hedonic and homeostatic pathways involved in energy expenditure and obesity.
The primary homeostatic regulatory area in the CNS is the hypothalamus, which consists of distinct nuclei including the arcuate nucleus (ARC), the paraventricular nucleus (PVN), the lateral hypothalamic area (LHA), the dorsomedial nucleus (DMN) and the ventromedial nucleus (VMN).
Arcuate Nucleus (ARC): Contains two distinct neuronal populations with opposing effects: orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY) neurons and anorexigenic pro-opiomelanocortin (POMC) neurons.
Paraventricular Nucleus (PVN): An important area within the hypothalamus that plays a significant role in the regulation of energy homeostasis.
Ventromedial Nucleus (VMN): The VMN has an abundant population of glycoresponsive neurons, and brain-derived neurotrophic factor (BDNF) is highly expressed. BDNF acts through its receptor Tropomyosin receptor kinase B (TRKB) to regulate appetite in humans and mice.
Dorsomedial Nucleus (DMN): Serves as an important hypothalamic area that is involved in the regulation of appetite and other physiological processes (thermoregulation and stress).
Lateral Hypothalamic Area (LHA): Rich in orexin and MCH neurons and receives downstream project…