Physiologic changes in active weight loss versus maintenance of reduced weight

	Active weight loss	Maintenance of reduced weight
Current metabolic state	Negative energy balance	Energy balance
Changes compared with weight maintenance at usual body weight
Energy expenditure	↓↓ REE (approximately 2 times reduced weight maintenance residual) ↓ NREE ↑ Muscle contraction efficiency	↓ REE* ↓ NREE* ↑ Muscle contraction efficiency*
Neuroendocrine axes	↓↓ T3, ↓↓ T4, ↓↓ TSH, ↑ rT3 ↓↓ Leptin/FM by 40 to 50%* ↑ Cortisol ↑ GH	↓ T3, ↓ T4, ↓ TSH, ↑ rT3* ↓ Leptin/FM by approximately 10%* Cortisol within normal range No change or small ↑ GH
Autonomics	↑↑ PNS tone and ↓↓ SNS tone	↑ PNS tone and ↓ SNS tone*
Energy intake	↓↓ Satiation ↑↑ Hunger	↓ Satiation* ↑ Hunger*

The arrows represent the direction and magnitude of the physiologic changes that occur to oppose active weight loss and/or maintenance of reduced weight. These illustrate that homeostatic systems functioning to maintain usual body weight are responsive to both energy stores (fat mass) and energy balance (weight loss versus weight maintenance).

REE: resting energy expenditure; NREE: non-resting energy expenditure; FM: fat mass; T3: triiodothyronine; T4: thyroxine; TSH: thyroid-stimulating hormone; rT3: reverse T3 (bioinactive enantiomer of T3); GH: growth hormone; PNS: parasympathetic; SNS: sympathetic nervous system.
* Significant reversal of physiologic changes by leptin repletion.

References:

Sumithran P, Proietto J. The defence of body weight: a physiological basis for weight regain after weight loss. Clin Sci (Lond) 2013; 124:231.
Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 2011; 365:1597.

Adapted with permission of Bioscientifica Limited. From: Rosenbaum M, Leibel RL. 20 years of leptin: role of leptin in energy homeostasis in humans. J Endocrinol 2014; 223:T83. Permission conveyed through Copyright Clearance Center, Inc.

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Physiologic changes in active weight loss versus maintenance of reduced weight