Hypothalamic GLP-1: the control of BAT thermogenesis and browning of white fat

Abstract

Brown adipose tissue (BAT) is a specialized organ responsible for thermogenesis, a process required for maintaining body temperature. Since the discovery that BAT and brite/beige cells are functional in adult humans, many studies have been focusing on the physiology and functionality of this organ. The brain is controlling the maintenance of body temperature through a complex neuronal network. One of the candidates to modulate thermogenesis at central level is glucagon-like peptide-1 (GLP-1), with GLP-1 receptors widely expressed throughout the brain. Our group has recently reported that stimulation of brain GLP-1 receptors in the ventromedial nucleus of the hypothalamus is essential for the activation not only of BAT thermogenesis, but also browning of white fat. Notably, both actions are mediated by specific inhibition of the energy sensor AMP-activated protein kinase (AMPK). In this commentary, we summarize the latest results on this topic, as well as the potential clinical relevance of the brain GLP-1 system to treat obesity.

Keywords:

• hypothalamus
• GLP-1
• brown adipose tissue
• sympathetic nervous system

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

This work has been supported by grants from Ministerio de Economia y Competitividad (CD: BFU2011-29102; RN: BFU2012-35255), Xunta de Galicia (ML: 2012-CP070; RN: EM 2012/039 and 2012-CP069), Fondo de Investigaciones Sanitarias (ML: PI12/01814), Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn). CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. The research leading to these results has also received funding from the European Community's Seventh Framework Programme under the following grant: CD, ML and RN: FP7/2007-2013: n° 245009: NeuroFAST and ERC StG 2011-OBESITY53-281408 to RN.