Nonhomeostatic control of human appetite and physical activity in regulation of energy balance

Abstract

Ghrelin and leptin, putative controllers of human appetite, have no effect on human meal-to-meal appetite but respond to variations in energy availability. Nonhomeostatic characteristics of appetite and spontaneous activity stem from inhibition by leptin and ghrelin of brain reward circuit that is responsive to energy deficit, but refractory in obesity, and from the operation of a meal-timing circadian clock.

Figure 1

Hunger ratings on a 10-cm visual analog scale in response to a 100 Kcal (open circles) or a 500 Kcal (solid circles) breakfast at 6 am, 550 Kcal exercise energy expenditure between 10 and 12 h, presence of intravenous replacement of 364 Kcal between 6 and 11 h, and ad-libitum food intake at 13 h in 10 postmenopausal women. Four treatment trials: a small meal (Rest), exercise (EX), and intravenous replacement of calories missing in the small meal (Rest-TPN) or expended during exercise (EX-TPN). A sedentary trial in which a large morning meal was provided (Sed) served as a control condition. TPN, total parenteral nutrients. [Adapted from Borer KT, Wuorinen E, Ku K, Burant C. Appetite responds to changes in meal content, whereas ghrelin, leptin, and insulin track changes in energy availability. J Clin Endocrinol Metab 2009;94:2290–2298. Copyright © 2009 The Endocrine Society. Used with permission.]

Figure 2

Ratings of fullness (left) and changes in the concentration of gastric insulinotropic peptide (GIP; right) in response to differences in meal size, exercise energy expenditure, and total parenteral nutrients (TPN). Symbols as in Figure 1. Four treatment trials: a small meal (Rest), exercise (EX), and intravenous replacement of calories missing in the small meal (Rest-TPN) or expended during exercise (EX-TPN). A sedentary trial in which a large morning meal was provided (Sed) served as a control condition. [Adapted from Borer KT, Wuorinen E, Ku K, Burant C. Appetite responds to changes in meal content, whereas ghrelin, leptin, and insulin track changes in energy availability. J Clin Endocrinol Metab 2009;94:2290–2298. Copyright © 2009 The Endocrine Society. Used with permission.]

Figure 3

Changes in plasma total ghrelin (left) and leptin (right) concentrations in response to differences in meal size, exercise energy expenditure and total parenteral nutrients (TPN). Symbols as in Figure 1. Four treatment trials: a small meal (Rest), exercise (EX), and intravenous replacement of calories missing in the small meal (Rest-TPN) or expended during exercise (EX-TPN). A sedentary trial in which a large morning meal was provided (Sed) served as a control condition. [Adapted from Borer KT, Wuorinen E, Ku K, Burant C. Appetite responds to changes in meal content, whereas ghrelin, leptin, and insulin track changes in energy availability. J Clin Endocrinol Metab 2009;94:2290–2298. Copyright © 2009 The Endocrine Society. Used with permission.]

Figure 4

Energy balance before (top), food consumed during (center), and energy balance after (bottom) the ad-libitum meal at 13 h. Four treatment trials: a small meal (Rest), exercise (EX), and intravenous replacement of calories missing in the small meal (Rest-TPN) or expended during exercise (EX-TPN). A sedentary trial in which a large morning meal was provided (Sed) served as a control condition. (Reprinted from Borer KT, Wuorinen E, Ku K, Burant C. Appetite responds to changes in meal content, whereas ghrelin, leptin, and insulin track changes in energy availability. J Clin Endocrinol Metab 2009;94:2290–2298. Copyright © 2009 The Endocrine Society. Used with permission.)

Figure 5

Circadian changes in human hunger (broken line) in a study where three ad-libitum meals (Ad-lib) were offered at 6 to 7 h intervals, and two 2-h periods of exercise (ex) of different intensity but equivalent work load were provided. Mod, moderate. Based on data from (35).

Figure 6

A concept of ultradian and nycthemeral oscillations in energy balance caused by a reciprocal relationship between the amount of food eaten and post-meal behavioral activation during day and suppression of both behaviors during night. Small meals (hatched line) lead to increased physical activity, while excess energy intake (broken line) suppresses locomotion.

Figure 7

The inverse relationship between spontaneous physical activity and body fat. Hatched vertical lines hypothetically define activity levels that should support body fat levels corresponding to body mass indices of between 20 and 30 kg/m².