12/26/2023 0 Comments Hedonic dysfunctionThis is true not only in people with ‘normal’ weights but also in people who are overweight or obese. Under such a homeostatic system, an individual's body weight in adulthood is usually maintained at a relatively constant level, fluctuating only slightly within a narrow range around the body weight ‘set point’. Overwhelming experimental evidence has now accumulated in support of a homeostatic regulatory system for body weight. The discovery of leptin in 1994 by positional cloning of the obese gene 8 marked the beginning of an era in which our knowledge of the neuroendocrine regulation of body weight rapidly expanded. The initial proposal of a lipostatic mechanism for body weight regulation in 1950 1 triggered an intense search for lipostatic signals, including various parabiotic rodent models 2- 4, which may act on the hypothalamic control centre 5- 7. The mechanism by which body weight is regulated by metabolic signals has been studied for several decades. Recognition of the two types of obesity may lead to more effective treatment and prevention of obesity. In contrast, when a steady-state weight is above the metabolic set point due to hedonic over-eating (‘hedonic obesity’), a persistent compensatory increase in energy expenditure per unit metabolic mass may be demonstrable. When overweight is due to elevation of the metabolic set point (‘metabolic obesity’), energy expenditure theoretically falls onto the standard energy–mass regression line. While hedonic signals are potent influences in determining food intake, metabolic regulation involves the active control of both food intake and energy expenditure. However, an elevated steady-state body weight may also be achieved without an alteration of the metabolic set point, via sustained hedonic over-eating, which is governed by the reward system of the brain and can override homeostatic metabolic signals. The metabolic body weight set point has a genetic basis, but exposure to an obesogenic environment may elicit allostatic responses and upward drift of the set point, leading to a higher maintained body weight. Metabolic regulation of body weight centres around the ‘body weight set point’, which is programmed by energy balance circuitry in the hypothalamus and other specific brain regions. Body weight is determined via both metabolic and hedonic mechanisms.
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