Introduction:
Obesity is a complex condition involving an interplay between several environmental and diet factors and an individual’s body. It can be defined as an abnormal and excessive accumulation of fat in the body that can impair health. A recent study has predicted that by the year 2035 more than half of the world’s population will be obese. Overweight and obesity were once thought as a problem in high-income countries, but are now substantially on an upward trend in low- and middle-income countries as well, especially in urban areas; it is considered a modern epidemic. Obesity has got to do with much more than the way one looks, it is a risk factor for many diseases such as heart diseases, diabetes, certain types of cancers, sleep apnea, etc. There has always been a lot of buzz around healthy ways to lose fat and a never ending research on scientific and evidence based lifestyle practices and dietary habits to keep obesity at bay. Obesity is discerned using the body mass index (BMI); a BMI value above 30.0 falls in the obese category. For Asian populations a BMI greater than 23 is considered as a risk factor for various health conditions. However, athletes may have a BMI falling in the overweight category but they are not obese; other measurements like waist circumference are also taken into consideration rather than just absolute weight.
How Does Obesity Affect the Body?
The mechanical implication of obesity is extra pressure on the skeleton and joints. Chemical changes in blood due to excessive fat increase the likelihood of life-threatening events like heart disease and stroke. Overall obesity is related to a premature death from various causes. It leads to metabolic changes. Excess calories are stored as lipids in the adipose tissue. When there is no more tissue left to store the excess calories, fat cells become enlarged and start secreting hormones and chemicals. This kicks off a chronic inflammatory process in the body which contributes to several diseases. Insulin resistance, high blood sugars and lipids constitute a metabolic syndrome.
What Is Ghrelin?
Ghrelin is a hormone produced and released by the stomach responsible for signaling the brain and stimulating hunger. While it is primarily produced in the stomach, other organs such as the small intestine, pancreas and the brain itself secrete small amounts of ghrelin. It not only stimulates hunger through a metabolic-need driven homeostatic feeding, but also acts centrally, modulating reward, memory and motivated feeding behavior. Structurally it is composed of 28 amino acids and is an acylated peptide.
What Are Its Functions?
The key functions of ghrelin include:
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Signals the hypothalamus leading to increased appetite.
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Promotes storage of fat.
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Pituitary gland stimulation by ghrelin leads to growth hormone release.
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Acts on the digestive system to propel the movement of food from the stomach to the intestines.
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Has a role in the control of insulin release.
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Protects cardiovascular health.
The release of growth hormone from the pituitary gland triggered by ghrelin breaks down fat tissue, controls insulin release, and protects the heart.
How Is Ghrelin Related to Appetite and Obesity?
Ghrelin levels peak when the stomach is empty and plummet after consumption of a meal. Nicknamed as the ‘hunger hormone’ it is the only circulating orexigenic (appetite stimulating) hormone and affects intestinal motility and emptying. Researchers believe that ghrelin has an impact on both long term and short term body weight. Contrary to what one might expect, obese individuals were found to have low levels of circulating ghrelin. However, it has been found that postprandial suppression of ghrelin is weaker in obese groups compared to controls with normal BMI; this is a reasonable explanation for the increased food consumption in obese individuals since they experience a sense of hunger even after eating a meal. The two most popular approaches to managing obesity are, a conservative approach involving diet, exercise and lifestyle changes and a surgical approach by surgical weight reduction procedures. The interaction between ghrelin and these measures are as follows:
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Ghrelin and Dieting - Dieting for weight loss can include smaller portions of food at short intervals or avoidance of certain elements of food, or fasting periodically. There are multiple types of diets each advocated for its own benefits. Diets and dietary-induced weight loss have been related to an increase in ghrelin levels in the blood, which could explain why diets fail so frequently. When we limit our calorie intake and/or lose weight, our bodies interpret it as famine. Consequently, a compensatory process to maintain our weight is activated. Our metabolism slows down and we become hungry, we tend to eat more. Dieters who rely solely on willpower to reduce weight generally fail. Ghrelin, in addition to stimulating appetite, may also promote the accumulation of belly fat.
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Ghrelin and Bariatric Surgery - Bariatric surgery has produced impressive results in morbidly obese individuals. The roux-en-y gastric bypass (RYGB) surgery is a type of bariatric surgery in which a small pouch in the stomach is created and connected directly to the small intestine. Another procedure called sleeve gastrectomy (SG) involves the removal of the gastric fundus which is a major site of ghrelin production; hence ghrelin levels fall sharply following SG which could be a contributing factor to the procedure’s success. RYGB causes malabsorption due shunting of the undigested food to the distal part of the small intestine.
To summarize, the proven role of ghrelin in obesity is either due to its overproduction or inadequate suppression following meal consumption. Some individuals may have greater receptor sensitivity for ghrelin action. Diet or dietary-induced weight loss is associated with increased ghrelin levels which could be the reason why there is rebound weight gain due to increased appetite. Changes in the orexigenic hormone ghrelin play a significant role in hunger fluctuation after meals and the maintenance of weight loss accomplished after bariatric surgery.
Can Ghrelin Inhibitors Be the Answer?
The role of ghrelin in appetite makes us wonder if inhibiting this hormone to decrease hunger and food consumption could be a plausible solution. In 2006, the Scripps Research Institute in California developed an anti-obesity ghrelin vaccine which helped reduce fat and slow down weight gain in animal studies. However, ghrelin is also associated with pleasure derived from food and completely blocking this hormone may have side effects. Nevertheless, ghrelin blockers could well be the future in combating obesity.
Conclusion:
Ghrelin is a hormone that stimulates hunger, discovered only about two decades back. Researchers suggest that excessive production of ghrelin or an exaggerated sensitivity to the hormone can be a factor in obesity. The precise role of ghrelin in the pathophysiology of obesity is yet unknown due to limitations such as challenges to the actual measurement of ghrelin levels and limited number of randomized control trials and studies. Nevertheless, a well-defined explanation and knowledge of the onset of appetite by an increase in ghrelin levels could be revolutionary, opening up new avenues for the management or even therapy of obesity.
