Changes from baseline in energy balance and homeostatic systems during maintenance of a 10% or greater reduced body weight and their responsiveness to exogenous leptin in individuals who initially had obesity or never had obesity (Rosenbaum and Leibel, 2014). Energy expenditure due to physical activity is calculated as the difference between direct measurement of 24-h energy expenditure and measurement of resting energy expenditure plus diet-induced thermogenesis. Eating behavior, including energy intake, is examined by visual analog scales during a fixed liquid formula meal, kcal of the liquid formula consumed to reach satiation, and by fMRI studies of brain responses to food. Assessments of autonomic nervous system activity were made by analyses of heart rate variability during sequential blockade of the parasympathetic and sympathetic nervous systems with atropine and esmolol, respectively, and by 24-h urine catecholamine excretion. Skeletal muscle contractile efficiency was measured by graded bicycle ergometry. Myosin heavy chain (MHC) and sarcoplasmic endoplasmic reticulum Ca++-dependent ATPase (SERCA) muscle gene expression studies were done by mRNA quantification in biopsies of vastus lateralis muscle. All phenotypes opposing sustained weight loss are responsive to leptin repletion except for PNS tone and TSH which are underlined in blue. SNS, sympathetic nervous system; PNS, parasympathetic nervous system; T3, triiodothyronine; T4, thyroxine; rT3, reverse T3; TSH, thyroid stimulating hormone; MHC, myosin heavy chain; SERCA, sarcoplasmic endoplasmic reticulum Ca++-dependent ATPase (Figure created with BioRender.com).