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Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase.

Valentina Capelli1,2,3, Carmen Grijota-Martínez4, Nathalia R V Dragano1,2

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Peripheral thyroid hormone (TH) administration impacts energy balance through both central and local mechanisms. This study clarifies TH

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Area of Science:

  • Endocrinology
  • Metabolism
  • Neuroendocrinology

Background:

  • Thyroid hormones (TH) regulate energy homeostasis, acting on both peripheral tissues and the hypothalamus.
  • The relative contribution of central versus peripheral TH effects remains unclear, especially under physiological conditions of peripheral TH release.

Purpose of the Study:

  • To investigate the impact of peripherally administered TH on hypothalamic and peripheral metabolic status.
  • To elucidate the central and local mechanisms by which peripheral TH influences energy balance.

Main Methods:

  • Utilized two models of peripherally induced hyperthyroidism via oral administration of thyroxine (T4) and triiodothyronine (T3).
  • Assessed serum and hypothalamic TH levels, feeding behavior, growth, body temperature, body composition, and adipose tissue (brown and white) and liver metabolism.
  • Measured uncoupling protein 1 (UCP1) levels and activity, and hypothalamic AMP-activated protein kinase (AMPK) signaling.

Main Results:

  • Peripheral TH administration significantly altered feeding behavior, growth, core body temperature, body composition, and liver metabolism.
  • Observed changes in brown adipose tissue (BAT) morphology and activity, including increased uncoupling capacity and white adipose tissue (WAT) browning.
  • Demonstrated significant changes in hypothalamic TH concentrations, with T3 administration downregulating hypothalamic AMPK, indicating central effects.

Conclusions:

  • Peripherally administered TH modulate energy balance through diverse mechanisms, affecting both central and peripheral targets.
  • The study provides a unified view of centrally mediated and local metabolic effects of TH in hyperthyroidism.
  • Peripheral TH administration influences lipid metabolism, shifting it from WAT accumulation towards BAT utilization.