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Obesity and Weight Loss

Regulation of Body Weight

Our system of energy balance evolved to ensure that a healthy person maintained adequate reserves of body fat to sustain life through repeated times of food scarcity, including famine. Food energy abundance is a relatively recent phenomenon, quite dissimilar to the vast majority of time over the past 100 000 years. In fact, body weight maintenance is achieved by the very complex and interrelated interaction of neurological and hormonal factors, with the goal of increasing appetite and preserving body fat when energy stores are low. Within the brain, a region called the hypothalamus monitors and integrates neurological signals and modulates appetite accordingly. Sensory cells located within the stomach walls that detect stretching of stomach tissue can directly signal satiety to the brain through nerve impulses. Indirectly, blood levels of glucose, fatty acids, and amino acids (components of proteins) stimulate the perception of satiety in brain centers and depress eating behavior. Additionally, a variety of hormones released at various levels of the gastrointestinal tract perform numerous functions in the balance of energy intake and utilization. Insulin (released from the pancreas and critical for the uptake of glucose into cells) and cholecystokinin (CCK) (secreted by the upper part of the small intestine and important for triggering release of digestive enzymes and bile) are also potent satiety signals (Marieb 2010).   

In addition, fat stores in the body are able to relay the overall state of energy storage to the brain through the secretion of the hormone leptin (Marieb 2010). Leptin is secreted into the blood by adipose (fat) cells in proportion to their levels of stored fats. It travels to the brain and acts upon the hypothalamus, stimulating the release of neurotransmitters that signal satiety, and suppressing those that signal hunger. Thus, leptin released by adipose tissue provides the brain with information on long-term energy economy, and allows it to adjust food intake accordingly (Begg 2012). However, this intricate system of appetite control can become perturbed in obesity, as excess fat stores contribute to chronically elevated leptin levels. This leads to down regulation of cellular sensitivity to the effects of leptin, a physiologic state known as leptin resistance. Weight loss efforts put forth by obese individuals may be undermined by failure of the leptin system to suppress their appetite, resulting in excessive hunger (Myers 2010).  

Another hormone derived from fat cells, called adiponectin, is an anti-obesity signaling molecule; adiponectin signaling is disrupted in obesity-related diseases and states of insulin resistance (Shehzad 2012). Evidence suggests that leptin and adiponectin can work together to combat insulin resistance (Yamauchi 2001; Kadowaki 2011; Siasos 2012). Optimizing fat cell signaling thus represents an important aspect of any comprehensive weight-loss strategy.

Resting energy expenditure (REE) also influences weight gain and progression to obesity. REE is the rate at which metabolic activity burns calories during periods of rest or inactivity. Having a low REE may contribute to weight gain or make it difficult to lose weight. Studies show that REE is directly related to serum adiponectin levels, and that higher leptin levels (as occurs in leptin resistance; see below) are associated with decreased REE (Brusik 2012). Aging is also associated with decreased REE (Hunter 2001; Bosy-Westphal 2003). These findings suggest that boosting REE could be a valuable strategy to mitigate age-related weight gain.