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Central transthyretin acts to decrease food intake and body weight.

Fenping Zheng1,2, Yonwook J Kim1, Timothy H Moran1

  • 1Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

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Central transthyretin (TTR) acts as an appetite suppressant, reducing food intake and body weight. This finding reveals TTR

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Metabolism

Background:

  • Transthyretin (TTR) primarily functions as a transporter for thyroxine and retinol in blood and cerebrospinal fluid.
  • Elevated Ttr gene expression in the dorsomedial hypothalamus (DMH) of rats with anorexia suggests a role in regulating food intake and energy balance.

Purpose of the Study:

  • To investigate the effects of central Transthyretin (TTR) on food intake and body weight in rats.
  • To identify hypothalamic signaling pathways influenced by brain TTR that may mediate its feeding effects.

Main Methods:

  • Intracerebroventricular (icv) administration of TTR in normal growing rats.
  • Assessment of food intake, body weight, and conditioned taste aversion.
  • Measurement of neuropeptide Y (NPY) levels in the hypothalamus (DMH and paraventricular nucleus).
  • Chronic icv TTR infusion in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

Main Results:

  • ICV TTR administration significantly decreased food intake and body weight in normal rats without inducing sickness or taste aversion.
  • ICV TTR reduced neuropeptide Y (NPY) levels in the DMH and paraventricular nucleus.
  • Chronic TTR infusion in obese OLETF rats reversed hyperphagia and obesity, accompanied by reduced DMH NPY levels.

Conclusions:

  • Central Transthyretin (TTR) exerts a previously unrecognized anorectic effect, influencing energy balance.
  • TTR's action involves the modulation of hypothalamic NPY signaling.
  • Central TTR represents a potential therapeutic target for obesity and associated metabolic disorders.