FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss, 2014, Owen et al

[SNT Gatchaman]

FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss
Bryn M. Owen, Xunshan Ding, Donald A. Morgan, Katie Colbert Coate, Angie L. Bookout, Kamal Rahmouni, Steven A. Kliewer, David J. Mangelsdorf

The mechanism by which pharmacologic administration of the hormone FGF21 increases energy expenditure to cause weight loss in obese animals is unknown. Here we report that FGF21 acts centrally to exert its effects on energy expenditure and body weight in obese mice. Using tissue-specific knockout mice, we show that βKlotho, the obligate co-receptor for FGF21, is required in the nervous system for these effects. FGF21 stimulates sympathetic nerve activity to brown adipose tissue through a mechanism that depends on the neuropeptide corticotropin-releasing factor. Our findings provide an unexpected mechanistic explanation for the strong pharmacologic effects of FGF21 on energy expenditure and weight loss in obese animals.

Link | PDF

 

[SNT Gatchaman]

Within the nervous system, βKlotho is expressed in the suprachiasmatic nucleus (SCN) in the hypothalamus, and the area postrema, nucleus of the solitary tract and nodose ganglia, which although they are discrete anatomical nuclei, comprise the dorsal-vagal complex (DVC).

These would be brain areas relating to circadian rhythms, autonomic functioning and cardiovascular sensing and rate/tone control.

From Wikipedia —

The neurons in the inferior ganglion of the vagus nerve innervate the taste buds on the epiglottis, the chemoreceptors of the aortic bodies and baroreceptors in the aortic arch. Most importantly, the majority of neurons in the inferior ganglion provide sensory innervation to the heart, respiratory and gastrointestinal tracts and other abdominal organs as the urinary bladder.