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Am J Physiol Endocrinol Metab. 2018 Jun 19. doi: 10.1152/ajpendo.00116.2018. [Epub ahead of print]

Triiodothyronine and leptin repletion in humans similarly reverse weight-loss induced changes in skeletal muscle.

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Pediatrics and Medicine, Columbia University, United States.
Department of Medicine, Division of Cardiology, Columbia University Medical Center.
Department of Physiology and Biophysics, University of California at Irvine, United States.
Department of Physiology and Biophysics, University of California-Irvine, United States.
Anesthesia, Columbia University College of P&S.
Obesity Research Center, Columbia University, St. Luke's-Roosevelt Hospital, United States.
Departments of Pediatrics and Medicine, Division of Molecular Genetics, Columbia University Medical Center.


Subjects maintaining a 10% or greater dietary weight loss exhibit decreased circulating concentrations of bioactive thyroid hormones and increased skeletal muscle work efficiency largely due to increased expression of more efficient myosin heavy chain isoforms (MHCI) and significantly mediated by the adipocyte-derived hormone leptin. The primary purpose of this study was to examine the effects of triiodothyronine (T3) repletion on energy homeostasis and skeletal muscle physiology in weight-reduced subjects and to compare these results with the effects of leptin repletion. Nine healthy inpatient subjects with obesity were studied at usual weight (Wtinitial) and following a 10% dietary weight loss while receiving 5 weeks of a placebo (Wt-10%placebo) of T3 (Wt-10%T3) in a single blind crossover design. Primary outcome variables were skeletal muscle work efficiency and vastus lateralis muscle mRNA expression. These results were compared to the effects of leptin repletion in a population of 22 subjects some of whom were previously reported. At Wt-10%placebo there were significant increases in skeletal muscle work efficiency and in the relative expression of the more efficient/less efficient MHCI/MHCII isoforms, and a decrease in the ratio of the less efficient/more efficient SERCA1/SERCA2 isoforms. These changes were largely reversed by T3 repletion to a degree similar to that occurring with leptin repletion. These data support the hypothesis that the effects of leptin on energy expenditure in weight-reduced individuals are largely mediated by T3 and suggest that further study of the possible role of thyroid hormone repletion as adjunctive therapy to help sustain weight loss.


Energy Homeostasis; Leptin; Muscle; Thyroid; Weight Loss


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