Bariatric Times

NOV 2017

A peer-reviewed, evidence-based journal that promotes clinical development and metabolic insights in total bariatric patient care for the healthcare professional

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11 Review Bariatric Times • November 2017 e nteroendocrine "I" cells in the upper small bowel release CCK in response to food high in protein and fat. The enteroendrocrine "L" cells in the lower small bowel and colon release G LP-1 upon detection of carbohydrates and fats. GLP-1 is also an incretin that can stimulate the pancreas to secrete insulin in response to high carbohydrate intake a nd increased blood sugar levels. 7 CCK, PYY, and GLP-1 also induce satiety and, therefore, have an anorexigenic effect. While the incretin effect of hormones, such as insulin a nd amylin, are well known for the role they play in diabetes, their role in obesity to decrease food intake by stimulating POMC/CART neurons in the ARC is a more recent and i ntriguing discovery. 9 O xyntomodulin (OXM) is released post-prandially along with GLP-1 from enteric L-cells and serves as an appetite suppressant but has little to no incretin effect like G LP-1. Exogenous administration of OXM has been shown not only to reduce food consumption but also increase energy expenditure. 6 Pre- prandial injections are a notable barrier to OXM's utility as a weight loss agent. Blockade of the vagus nerve has been shown to interrupt signaling from these aforementioned peptides, which in turn prevents gastric distension, delays gastric emptying, and prevents communication of ghrelin with the hypothalamus to deliver its hunger message. ADIPOSITY AND HORMONES THAT INFLUENCE ENERGY HOMEOSTASIS Adipose tissue produces various hormones, but the most influential in terms of appetite regulation and energy stores is leptin. Leptin was one of the first hormones that was recognized to highly influence the body's fat storage. Mutations of the leptin gene result in morbid obesity, and increased expression of the gene results in energy expenditure and weight loss. 6 Leptin receptors are located in the ARC of the hypothalamus. Leptin inhibits NPY/AgRP neurons and stimulates POMC/CART neurons. Individuals with obesity display elevated levels of circulating leptin but without a corresponding clinical response of decreased appetite. This likely reflects leptin receptor resistance. Elevated, circulating levels of leptin and subsequent leptin resistance have been linked to pancreatic β-cell dysfunction, insulin resistance, and interference with GLP-1 secretion (13). Leptin could, therefore, play a significant role in the relationship between obesity and type 2 diabetes. Conversely, there is a drastic reduction in leptin levels following bariatric surgery, which leads to the resolution of type 2 diabetes. While GI peptides, such as GLP-1, PYY, C CK, and OXM, have more impact on short-term regulation of food consumption and are released in response to nutrient sensing in the gut, leptin has more of an impact on l ong-term energy intake. 1 4 L eptin appears to regulate energy intake, energy expenditure, and weight homeostasis. 15 Fasting and postprandial levels of g hrelin are lower in patients with obesity versus those of normal weight. 7 "Grazing" type behavior in p atients with obesity could in part be due to plateaued levels of ghrelin as opposed to the sharp drop in postprandial ghrelin in lean individuals. Postprandial levels of CCK, GLP-1, and P YY are reduced in patients with obesity versus lean subjects. 16 Considering that the primary role of these three gut peptides in appetite suppression is delayed gastric e mptying, altered levels in patients with obesity could explain why they might feel less satiated after a meal. IMPACT OF NON-SURGICAL VERSUS SURGICAL-INDUCED WEIGHT LOSS ON APPETITE- REGULATING PEPTIDES Several studies have examined the i mpact of diet and exercise —(non- surgical) induced weight loss on appetite regulating peptides as one method to explain why patients who achieve clinically significant weight l oss (~4–10% of their body weight) with lifestyle modification alone regain roughly 30 percent of the

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