Thyroid hormones induce browning of white fat

Area of Science:

• Endocrinology
• Metabolism
• Neuroscience

Background:

• Thyroid hormones (THs) are traditionally viewed as regulators of brown adipose tissue (BAT) thermogenesis via sympathetic outflow.
• Recent findings suggest THs directly influence hypothalamic pathways, inhibiting AMP-activated protein kinase (AMPK) to boost thermogenesis and promote weight loss.
• The role of THs in the browning of white adipose tissue (WAT) and its central regulation remains largely unexplored.

Purpose of the Study:

• To investigate the central effects of thyroid hormones (THs) on the browning of white adipose tissue (WAT).
• To elucidate the role of the ventromedial nucleus of the hypothalamus (VMH) and AMP-activated protein kinase (AMPK) in TH-induced WAT browning.

Main Methods:

• Induction of hyperthyroidism using thyroxine (T4) in animal models.
• Central and VMH-specific administration of triiodothyronine (T3).
• Genetic manipulation of hypothalamic AMPK in the VMH.
• Analysis of WAT browning markers and correlation with serum T4 levels in human WAT.

Main Results:

• T4-induced hyperthyroidism significantly promoted WAT browning.
• Central or VMH-specific T3 administration mimicked the WAT browning effect.
• Genetic activation of VMH AMPK reversed the T3-induced browning effect.
• Expression of browning genes in human WAT correlated with serum T4 levels.

Conclusions:

• Thyroid hormones (THs) induce white adipose tissue (WAT) browning.
• This TH-induced WAT browning is mediated by central effects within the hypothalamus, specifically involving the VMH and AMPK signaling.
• These findings highlight a novel mechanism for THs in regulating energy balance and thermogenesis through WAT browning.