Leptin and the regulation of body weight
The assimilation, storage and use of energy from nutrients are essential for life. In humans, the ability to store sufficient quantities of energy-dense triglycerides in fat tissue, allowed survival during the periods of food deprivation encountered during human evolution. However, the presence of excess fat tissue can be counterproductive. Our complex physiological system has evolved to regulate fuel stores and energy balance at an optimum level. Leptin, a hormone secreted by fat tissue, is a very important component of this system. Leptin also signals our nutritional status to several other body systems and modulates their function.
There is intense pressure to be ‘thin’ in late-twentieth-century ‘western’ societies. However, obesity is a prevalent condition and actual scientific data indicates that life expectancy is reduced when body-mass index (BMI, body mass in kg/square of the height in metres) is 20% or more above the ideal. The ideal BMI is the level at which life expectancy is maximal, and a BMI of >30 is now considered to represent obesity. The health risk of obesity is largely a consequence of diabetes, hypertension and heart disease, whose incidence increases with BMI.
The belief that obesity is largely the result of a lack of willpower is unsatisfactory. Many studies of twins, adoption studies of obesity, all indicate that obesity is the result of both genetic and environmental factors. Moreover, weight is stable in lean and obese individuals even though much of the population actively practices weight control. Also, many obese individuals eventually regain the lost weight after a diet.
The relative stability of weight in individuals indicated that energy balance may be controlled by our hypothalamus, which maintains constancy of total body energy stores. It has been proposed that signals reflecting nutritional state are sensed by the hypothalamus, which, in turn, modulates food intake and energy expenditure.
Leptin is also important in regulating the onset of puberty. Extremely thin women often stop ovulating and abnormally thin adolescent women enter puberty later than their heavier counterparts, indicating that fat tissue may produce a signal that regulates reproduction. This factor may be leptin.
These observations led to speculation that leptin’s main physiological role is to signal nutritional status during periods of food deprivation. It appears that dynamic changes in plasma leptin concentration act to resist weight change in either direction.
The role of leptin in obesity can be measured. An increase in plasma leptin suggests that obesity is the result of resistance to leptin. A low or normal plasma concentration of leptin in obesity suggests decreased production of leptin. This interpretation is similar to that used in studies of insulin and type I and type II diabetes.
Plasma leptin concentration correlates with body fat content and is usually increased in obese subjects. This suggests that human obesity is generally associated with a resistance to leptin. However, 5–10% of obese human subjects have relatively low levels of leptin, indicative of a reduced rate of leptin. Low leptin levels also predispose potentially to weight gain.
In humans, diet-induced weight loss results in a decrease in plasma leptin concentration. This may explain the high failure rate of dieting, as low leptin is likely to be a potent stimulus to weight gain. Anorexia nervosa patients also have extremely low leptin levels. Refeeding of these patients results in a rapid increase in plasma leptin concentration to roughly normal levels before normal weight is achieved. Thus, excessive leptin production could play a permissive role in the pathogenesis of this condition.
The latest research suggests that a plant based chemical called Withaferin A may restore leptin and glucose levels and ultimately help weight loss.
Each patient who attends our clinic for weight loss or weight management purposes will be referred for leptin testing; this is the very basis for our customized patient diet plans with the aim of achieving the desired results.