**4. Gastrointestinal, hormonal, and Genetics factors for weight regain**

There are known more than 30 gut hormone genes expressed and more than 100 bioactive peptides distributed in the gastrointestinal tract, which makes it the largest endocrine organ in the body [15, 17]. Several hormones in Gastrointestinal tract, which contribute to increase or decrease of food intake and in experimental studies, are directly associated with nutrition and body weight. That is the family of so-called PP-Fold Proteins. They consist of neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP). PYY and PP are secreted from gastrointestinal tract, whereas NPY is predominantly distributed within central nervous system [23]. Circulating PYY concentrations are low in fasted state and rise rapidly following a meal with a peak at 1–2 hours and remain elevated for several hours [24]. In both lean and obese humans, intravenous injection of PYY reduces appetite and food intake, suggesting that, unlike leptin, the sensitivity of PYY is preserved in obese subjects. Pancreatic Polypeptide (PP). PP is secreted from PP cells in the pancreatic islets of Langerhans. The anorectic effects of PP have been demonstrated in several experimental models. In leptin-deficient mice, repeated intraperitoneal injection of PP decreases body weight gain and ameliorates insulin resistance and hyperlipidemia [15]. GLP-1R is widely distributed particularly in the brain, GI tract, and pancreas [10]. It is known from experimental studies that circulating GLP-1 levels rise after a meal and fall in the fasted state. GLP-1 is associated with reduced food intake, and it can suppress glucagon secretion, leading to delayed gastric emptying [21]. Clinical trials in normal weight and obese subjects have also shown a reduction of food intake after a dose-dependent intravenous infusion of GLP-1. It is also known that Morbid obese patients have a blunted postprandial GLP-1 response compared to normal weight patients. GLP-1 is investigated about its potent incretin effect in addition to its anorectic action. That means that it can stimulate insulin secretion in a glucose-dependent manner following ingestion of carbohydrate. Experimental studies about application of Ozempic in clinical practice have confirmed positive effect of continuous subcutaneous infusion of GLP-1 to patients with type 2 diabetes for 6 weeks. GLP-1 infusion reduces appetite, body weight and improves glycemic control [25]. Research studies about the effect of Ozempic and Trulicity as Once-weekly subcutaneous injection have demonstrated greater improvements in glycemic control and weight loss in patients with Diabetes type 2 (DT2) and Obesity. On the other hand, Ghrelin is the only known orexigenic gut hormone involved in the mechanism of Morbid Obesity. Levels of circulating ghrelin increase before meal and fall rapidly in after meal period [25]. Fasting plasma levels of ghrelin are high in patients with anorexia nervosa [21] and in subjects with dietinduced weight loss. By contrast, obese patients have a less marked drop in plasma ghrelin after meal injection [25]. Dysregulation of ghrelin secretion is also implicated in the mechanism through which sleep disturbance contributes to Obesity. Subjects with short sleep duration have elevated ghrelin levels, reduced leptin, and high Body Mass Index (BMI) compared with patients with normal BMI and normal sleep duration [21].

#### *Predicting Factors for Weight Regain after Bariatric Surgery DOI: http://dx.doi.org/10.5772/intechopen.108715*

Some authors as De Silva et al. [15] have investigated the brain function of obese patients during exposure to food pictures and intravenous infusion of Ghrelin with so-called functional magnetic resonance imaging. The investigations have revealed increased activation in the amygdala, orbitofrontal cortex, anterior insula, and striatum Furthermore, there are hypotheses that suggest that effects of ghrelin on the response of amygdala and orbitofrontal cortex are correlated with self-rated hunger ratings. Cholecystokinin (CCK) is another known gut hormone, which plays a role in food intake [25]. The experimental model confirms that CCK is secreted postprandially by the I cell of the small intestine into circulation, and it has a short plasma half-life of a few minutes. The investigations and studies into the function of Gastrointestinal hormones reveal that they play a significant role as mediators and triggering factors of weight regain in each patient. The process of investigation and adaptation of appropriate laboratory or Clinical tests to confirm that in clinical practice is too far now! However, the understanding and knowledge about secretion and expression of Gastrointestinal hormones can give us the basic selection criteria of Bariatric/Metabolic procedures in candidates of weight loss surgery and predict the long-term results of achieved or expected weight loss or weight regain.

The weight loss response after B/MS varies widely between individuals [6]. A part of this variation is probably due to genetic factors, as close biological relatives tend to have quite similar responses to weight loss interventions [19]. Several studies have tried with limited success to explore the significance of potential specific genetic determinants of the individual variation in weight loss after B/MS [2, 4, 5, 7, 8]. Reported studies of patients undergoing weight loss surgery have also pointed out a relationship between weight loss and genetic markers, associated with abdominal obesity. Anatomy and physiology of human body are individual; however, the polymorphisms of body fat distribution have been suggested to control the growth of human adipose tissue in three main pathways. The first one is so-called Adipogenesis. The second one is known as angiogenesis, and the third one is named as non-specified transcriptional regulation [26]. The first two pathways are responsible for adipose tissue function and expansion. The impairment of those two mechanisms can lead to metabolic disturbances through induction of hypoxia, inflammation, and fibrosis in the tissue [10]. The effects of fibrosis and reduced angiogenesis in adipose tissue are alerting factors for organ dysfunction in Morbid obese patients. Furthermore, fibrosis of adipose tissue may attenuate weight loss response after gastric bypass [1, 27]. Several hypotheses suggest that various genetic factors determinant for abdominal obesity and for weight loss responsiveness following surgical interventions may work via common pathways in adipogenesis and angiogenesis. One study has revealed that the association between Genetic Risk Score (GRS) and weight loss response to B/MS might be explained by the association between specific genetic markers and baseline anthropometrics, especially BMI [28]. Baseline BMI is known as a predicting factor for response to weight loss interventions. The choice of weight loss phenotype is therefore of great importance in this type of studies, investigating the association of weight loss and weight regain due to Genetic Factors. The same authors suggest that for mathematical reasons, the achieved BMI and excess weight loss variables are inversely associated with baseline BMI in B/MS cohorts [28]. Angiogenesis may be one of the mechanisms that govern the individual variation in response to weight loss treatment by possibly affecting adipose tissue flexibility.

Those studies open new horizons for surgical management of Morbid Obesity in patients with lower BMI but significant abdominal obesity and adipose tissue there. The studies also give the possibility to predict which procedures are most appropriate in such patients and what is the risk of WR on a long-term basis.
