Adaptive reduction in basal metabolic rate in response to food deprivation in humans: a role for feedback signals from fat stores

Abstract

We assessed the importance of lean and fat tissue depletion as determinants of the adaptive reduction in basal metabolic rate (BMR) in response to food deprivation by reanalyzing the data on BMR and body composition for the 32 men participating in the classic Minnesota experiment of semi-starvation and refeeding. We used individual data on BMR, body fat, and fat-free mass (FFM) assessed during the control (prestarvation) period, at weeks 12 and 24 of semistarvation (S12 and S24), and week 12 of restricted refeeding (R 12) to calculate an index of the reduction in thermogenesis at S12, S24, and R12, defined as the change in BMR adjusted for changes in FFM and fat mass, and an index of the state of depletion of the fat mass and FFM compartments at these times, defined as the deviation in fat mass or FFM relative to control values. The results indicated a positive relation between the reduction in thermogenesis and the degree of fat mass depletion (but not FFM depletion) during weight loss as well as during weight recovery (r = 0.5, P < 0.01). Furthermore, the residual variance was predicted by the initial (prestarvation) percentage fat and the cormic index (sitting height/height). Taken together, these results in normal-weight men responding to severe food deprivation reveal anthropometric predictors for human interindividual variability in the capacity for energy conservation and suggest that the adaptive reduction in BMR is partly determined by an autoregulatory feedback control system linking the state of depletion of fat stores to compensatory mechanisms that suppress thermogenesis.

Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance

“…(1) The value for extent of suppressed thermogenesis (as % of baseline basal metabolic rate) in healthy young men recovering body weight after semi-starvation is derived from the Minnesota Experiment of Keys et al 43 , and was determined in a reanalysis of the data on their basal metabolic rate after adjustments for changes in fat-free mass and in fat mass relative to pre-starvation values. 52 (2) In rats showing catch-up growth after post-weaning semi-starvation, REE is taken as their total energy expenditure (essentially sedentary) relative to that of weight-matched controls consuming the same amount of energy and gaining protein mass at the same rate, whether during re-feeding on a low-fat diet or on an isocaloric diet rich in animal saturated fat. 47,48,58 (3) In the group of healthy elderly men with low birth weight relative to another group with high birth weight, REE was determined from measurements of both preprandial and postprandial REE adjusted for body weight and height; in this study by Kensara et al, the adjustments of REE for fat-free mass, muscle mass, non-muscular (fat-free soft tissue) mass, or for the ratio of muscle to non-muscle (fat-free soft tissue) mass also yielded lower REE values (by 8-12%) in the low-birth-weight group than in the high-birth-weight group.…”

“…A similar relationship was also found after the 12-week period of restricted re-feeding, i.e., the lower the degree of fat repletion, the greater the extent of reduction in residual BMR and hence the greater the degree of reduction in thermogenesis. 52 Taken together, the relationship between suppressed thermogenesis and fat depletion during phases of both weight loss and weight recovery indicates the operation of a control system with a negative feedback loop between thermogenesis and the state of depletion of fat stores.…”

“…In this autoregulatory feedback system, signals from the depleted adipose fat stores exert a suppressive effect on thermogenesis. Support for the existence of a control system linking depletion of fat stores and suppressed thermogenesis in humans comes from the re-analysis 45,52 of longitudinal data on changes in basal metabolic rate (BMR) and in body composition from the classic 'Minnesota Experiment' of semi-starvation and re-feeding. 43 In this study, 32 healthy men of normal body weight were subjected to 24 weeks of semistarvation (during which they lost w25% of initial body weight), followed by 12 weeks of restricted re-feeding on diets relatively low in fat (w20% fat by energy).…”

Clinical significance of adaptive thermogenesis

“…Few decades have passed now, as the first studies to test experimental starvation in human reported a decrease in EE above that explained by fat mass and fat-free mass losses, 7,[13][14][15][16][17] suggesting the presence of an adaptive component of thermogenesis in response to decreased energy intake. However, controversy arose over the years with regards to demonstrating this phenomenon in opposite circumstances, that is an increase in EE beyond expectation during overfeeding.…”

“…Indeed, it has been well demonstrated that the decrease in EE during energy restriction and weight loss programs can be greater than expected from the decrease in fat mass and fat-free mass, [3][4][5] despite these two variables accounting for over 82% of the variance in EE. [6][7][8][9][10] This paper thus specifically focuses on an adaptive reduction in EE in response to energy restriction that can be observed in any component of total EE, 3,4,11,12 traditionally divided into resting and non-resting EEs (including physical activity and non-exercise activity EEs), and thermic effect of food.…”