Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance

By Miguel López, Luis M. Varela, M. J. Vazquez, S. Rodriguez-Cuenca, Carmen R. González, V. Velagapudi, D. Morgan, E. Schoenmakers, K. Agassandian, Ricardo Lage and 12 more. Nature Medicine, 2010

688 citations recorded by the source corpus.

Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly, inhibition of thyroid hormone receptors in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid hormone–induced modulation of AMPK activity and lipid metabolism in the hypothalamus is a major regulator of whole-body energy homeostasis.

Subfields: Endocrine and Autonomic Systems, Physiology

View Paper: https://www.semanticscholar.org/paper/1e465d1c409ee78d97a30dead37e56c2c779a52f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrine and Autonomic Systems

1. Sushil Kumar Jain
2. D. Hardie

In Physiology

1. B. Cannon
2. J. Nedergaard
3. Sushil Kumar Jain
4. L. Sidossis
5. G. Brent
6. D. Hardie
7. B. Spiegelman
8. S. Kajimura

Citations in the corpus

• AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. (2011, background): “…balance in a cell-autonomous manner, AMPK is also modulated by numerous hormones and/or cytokines that regulate energy balance at the whole body level, including leptin, adiponectin, and ghrelin (Kahn et al. 2005); cannabinoids (Kola et al. 2006); and even thyroid hormones (Lopez et al. 2010).”
• Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans (2014, methodology): “Mitochondrial Respiration Mitochondrial function was determined by high-resolution respirometry (30).”
• Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies (2015, background): “Recent data suggest the role of thyroid hormone in the regulation of BAT thermogenic activity through modulation of hypothalamic fat metabolism.(404)”
• Nonshivering thermogenesis and its adequate measurement in metabolic studies (2011, background): “However, it now seems likely that even thyroid hormone thermogenesis emanates from brown adipose tissue, due to thyroid hormone stimulation of the areas in the brain that control brown adipose tissue activity (Sjögren et al., 2007; Lopez et al., 2010; Cannon and Nedergaard, 2010).”
• Thyroid hormone regulation of metabolism. (2014, background): “The increased energy demand may override the anorexic stimuli (164).”