Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation

Cell. 2018 Nov 29;175(6):1561-1574.e12. doi: 10.1016/j.cell.2018.10.016. Epub 2018 Nov 15.

Abstract

The molecular mediator and functional significance of meal-associated brown fat (BAT) thermogenesis remains elusive. Here, we identified the gut hormone secretin as a non-sympathetic BAT activator mediating prandial thermogenesis, which consequentially induces satiation, thereby establishing a gut-secretin-BAT-brain axis in mammals with a physiological role of prandial thermogenesis in the control of satiation. Mechanistically, meal-associated rise in circulating secretin activates BAT thermogenesis by stimulating lipolysis upon binding to secretin receptors in brown adipocytes, which is sensed in the brain and promotes satiation. Chronic infusion of a modified human secretin transiently elevates energy expenditure in diet-induced obese mice. Clinical trials with human subjects showed that thermogenesis after a single-meal ingestion correlated with postprandial secretin levels and that secretin infusions increased glucose uptake in BAT. Collectively, our findings highlight the largely unappreciated function of BAT in the control of satiation and qualify BAT as an even more attractive target for treating obesity.

Keywords: UCP1; energy balance; gut hormone; heat; inter-organ communication; metabolism; satiation; secretin; secretin receptor; thermogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / cytology
  • Adipocytes, Brown / metabolism*
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Eating*
  • HEK293 Cells
  • Humans
  • Lipolysis
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • Secretin / genetics
  • Secretin / metabolism*
  • Thermogenesis*

Substances

  • Secretin